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Sample records for bioanalytical method validation

  1. Comparative assessment of bioanalytical method validation guidelines for pharmaceutical industry.

    Science.gov (United States)

    Kadian, Naveen; Raju, Kanumuri Siva Rama; Rashid, Mamunur; Malik, Mohd Yaseen; Taneja, Isha; Wahajuddin, Muhammad

    2016-07-15

    The concepts, importance, and application of bioanalytical method validation have been discussed for a long time and validation of bioanalytical methods is widely accepted as pivotal before they are taken into routine use. United States Food and Drug Administration (USFDA) guidelines issued in 2001 have been referred for every guideline released ever since; may it be European Medical Agency (EMA) Europe, National Health Surveillance Agency (ANVISA) Brazil, Ministry of Health and Labour Welfare (MHLW) Japan or any other guideline in reference to bioanalytical method validation. After 12 years, USFDA released its new draft guideline for comments in 2013, which covers the latest parameters or topics encountered in bioanalytical method validation and approached towards the harmonization of bioanalytical method validation across the globe. Even though the regulatory agencies have general agreement, significant variations exist in acceptance criteria and methodology. The present review highlights the variations, similarities and comparison between bioanalytical method validation guidelines issued by major regulatory authorities worldwide. Additionally, other evaluation parameters such as matrix effect, incurred sample reanalysis including other stability aspects have been discussed to provide an ease of access for designing a bioanalytical method and its validation complying with the majority of drug authority guidelines. Copyright © 2016. Published by Elsevier B.V.

  2. Development and Validation of a Bioanalytical Method for Direct ...

    African Journals Online (AJOL)

    Erah

    2011-01-16

    Jan 16, 2011 ... Purpose: To develop and validate a user-friendly spiked plasma method for the extraction of diclofenac potassium that reduces the ... Keywords: Bioanalytical method, Diclofenac potassium, RP-HPLC method, NSAIDs, Plasma. Received: 16 ..... R. Enantiospecific Pharmacokinetic Studies on. Ketoprofen in ...

  3. Development and Validation of a Bioanalytical Method for Direct ...

    African Journals Online (AJOL)

    Purpose: To develop and validate a user-friendly spiked plasma method for the extraction of diclofenac potassium that reduces the number of treatments with plasma sample, in order to minimize human error. Method: Instead of solvent evaporation technique, the spiked plasma sample was modified with H2SO4 and NaCl, ...

  4. AAPS and US FDA Crystal City VI workshop on bioanalytical method validation for biomarkers.

    Science.gov (United States)

    Lowes, Steve; Ackermann, Bradley L

    2016-02-01

    Crystal City VI Workshop on Bioanalytical Method Validation of Biomarkers, Renaissance Baltimore Harborplace Hotel, Baltimore, MD, USA, 28-29 September 2015 The Crystal City VI workshop was organized by the American Association of Pharmaceutical Scientists in association with the US FDA to continue discussion on the bioanalysis of biomarkers. An outcome of the Crystal City V workshop, convened following release of the draft FDA Guidance for Industry on Bioanalytical Methods Validation in 2013 was the need to have further discussion on biomarker methods. Biomarkers ultimately became the sole focal point for Crystal City VI, a meeting attended by approximately 200 people and composed of industry scientists and regulators from around the world. The meeting format included several panel discussions to maximize the opportunity for dialogue among participants. Following an initial session on the general topic of biomarker assays and intended use, more focused sessions were held on chromatographic (LC-MS) and ligand-binding assays. In addition to participation by the drug development community, significant representation was present from clinical testing laboratories. The experience of this latter group, collectively identified as practitioners of CLIA (Clinical Laboratory Improvement Amendments), helped shape the discussion and takeaways from the meeting. While the need to operate within the framework of the current BMV guidance was clearly acknowledged, a general understanding that biomarker methods validation cannot be adequately depicted by current PK-centric guidelines emerged as a consensus from the meeting. This report is not intended to constitute the official proceedings from Crystal City VI, which is expected to be published in early 2016.

  5. Calculations for Adjusting Endogenous Biomarker Levels During Analytical Recovery Assessments for Ligand-Binding Assay Bioanalytical Method Validation.

    Science.gov (United States)

    Marcelletti, John F; Evans, Cindy L; Saxena, Manju; Lopez, Adriana E

    2015-07-01

    It is often necessary to adjust for detectable endogenous biomarker levels in spiked validation samples (VS) and in selectivity determinations during bioanalytical method validation for ligand-binding assays (LBA) with a matrix like normal human serum (NHS). Described herein are case studies of biomarker analyses using multiplex LBA which highlight the challenges associated with such adjustments when calculating percent analytical recovery (%AR). The LBA test methods were the Meso Scale Discovery V-PLEX® proinflammatory and cytokine panels with NHS as test matrix. The NHS matrix blank exhibited varied endogenous content of the 20 individual cytokines before spiking, ranging from undetectable to readily quantifiable. Addition and subtraction methods for adjusting endogenous cytokine levels in %AR calculations are both used in the bioanalytical field. The two methods were compared in %AR calculations following spiking and analysis of VS for cytokines having detectable endogenous levels in NHS. Calculations for %AR obtained by subtracting quantifiable endogenous biomarker concentrations from the respective total analytical VS values yielded reproducible and credible conclusions. The addition method, in contrast, yielded %AR conclusions that were frequently unreliable and discordant with values obtained with the subtraction adjustment method. It is shown that subtraction of assay signal attributable to matrix is a feasible alternative when endogenous biomarkers levels are below the limit of quantitation, but above the limit of detection. These analyses confirm that the subtraction method is preferable over that using addition to adjust for detectable endogenous biomarker levels when calculating %AR for biomarker LBA.

  6. Bio-analytical method development and validation of Rasagiline by high performance liquid chromatography tandem mass spectrometry detection and its application to pharmacokinetic study

    OpenAIRE

    Ravi Kumar Konda; Babu Rao Chandu; B.R. Challa; Chandrasekhar B. Kothapalli

    2012-01-01

    The most suitable bio-analytical method based on liquidâliquid extraction has been developed and validated for quantification of Rasagiline in human plasma. Rasagiline-13C3 mesylate was used as an internal standard for Rasagiline. Zorbax Eclipse Plus C18 (2.1 mmÃ50 mm, 3.5 μm) column provided chromatographic separation of analyte followed by detection with mass spectrometry. The method involved simple isocratic chromatographic condition and mass spectrometric detection in the positive ion...

  7. Systematic Development and Validation of a Thin-Layer Densitometric Bioanalytical Method for Estimation of Mangiferin Employing Analytical Quality by Design (AQbD) Approach.

    Science.gov (United States)

    Khurana, Rajneet Kaur; Rao, Satish; Beg, Sarwar; Katare, O P; Singh, Bhupinder

    2016-01-01

    The present work aims at the systematic development of a simple, rapid and highly sensitive densitometry-based thin-layer chromatographic method for the quantification of mangiferin in bioanalytical samples. Initially, the quality target method profile was defined and critical analytical attributes (CAAs) earmarked, namely, retardation factor (Rf), peak height, capacity factor, theoretical plates and separation number. Face-centered cubic design was selected for optimization of volume loaded and plate dimensions as the critical method parameters selected from screening studies employing D-optimal and Plackett-Burman design studies, followed by evaluating their effect on the CAAs. The mobile phase containing a mixture of ethyl acetate : acetic acid : formic acid : water in a 7 : 1 : 1 : 1 (v/v/v/v) ratio was finally selected as the optimized solvent for apt chromatographic separation of mangiferin at 262 nm withRf 0.68 ± 0.02 and all other parameters within the acceptance limits. Method validation studies revealed high linearity in the concentration range of 50-800 ng/band for mangiferin. The developed method showed high accuracy, precision, ruggedness, robustness, specificity, sensitivity, selectivity and recovery. In a nutshell, the bioanalytical method for analysis of mangiferin in plasma revealed the presence of well-resolved peaks and high recovery of mangiferin. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  8. Bio-analytical method development and validation of Rasagiline by high performance liquid chromatography tandem mass spectrometry detection and its application to pharmacokinetic study

    Directory of Open Access Journals (Sweden)

    Ravi Kumar Konda

    2012-10-01

    Full Text Available The most suitable bio-analytical method based on liquid–liquid extraction has been developed and validated for quantification of Rasagiline in human plasma. Rasagiline-13C3 mesylate was used as an internal standard for Rasagiline. Zorbax Eclipse Plus C18 (2.1 mm×50 mm, 3.5 μm column provided chromatographic separation of analyte followed by detection with mass spectrometry. The method involved simple isocratic chromatographic condition and mass spectrometric detection in the positive ionization mode using an API-4000 system. The total run time was 3.0 min. The proposed method has been validated with the linear range of 5–12000 pg/mL for Rasagiline. The intra-run and inter-run precision values were within 1.3%–2.9% and 1.6%–2.2% respectively for Rasagiline. The overall recovery for Rasagiline and Rasagiline-13C3 mesylate analog was 96.9% and 96.7% respectively. This validated method was successfully applied to the bioequivalence and pharmacokinetic study of human volunteers under fasting condition. Keywords: High performance liquid chromatography, Mass spectrometry, Rasagiline, Liquid–liquid extraction

  9. Bio-analytical method development and validation of Rasagiline by high performance liquid chromatography tandem mass spectrometry detection and its application to pharmacokinetic study.

    Science.gov (United States)

    Konda, Ravi Kumar; Chandu, Babu Rao; Challa, B R; Kothapalli, Chandrasekhar B

    2012-10-01

    The most suitable bio-analytical method based on liquid-liquid extraction has been developed and validated for quantification of Rasagiline in human plasma. Rasagiline- 13 C 3 mesylate was used as an internal standard for Rasagiline. Zorbax Eclipse Plus C18 (2.1 mm×50 mm, 3.5 μm) column provided chromatographic separation of analyte followed by detection with mass spectrometry. The method involved simple isocratic chromatographic condition and mass spectrometric detection in the positive ionization mode using an API-4000 system. The total run time was 3.0 min. The proposed method has been validated with the linear range of 5-12000 pg/mL for Rasagiline. The intra-run and inter-run precision values were within 1.3%-2.9% and 1.6%-2.2% respectively for Rasagiline. The overall recovery for Rasagiline and Rasagiline- 13 C 3 mesylate analog was 96.9% and 96.7% respectively. This validated method was successfully applied to the bioequivalence and pharmacokinetic study of human volunteers under fasting condition.

  10. Quantitative bioanalytical and analytical method development of dibenzazepine derivative, carbamazepine: A review ☆

    OpenAIRE

    Datar, Prasanna A.

    2015-01-01

    Bioanalytical methods are widely used for quantitative estimation of drugs and their metabolites in physiological matrices. These methods could be applied to studies in areas of human clinical pharmacology and toxicology. The major bioanalytical services are method development, method validation and sample analysis (method application). Various methods such as GC, LC–MS/MS, HPLC, HPTLC, micellar electrokinetic chromatography, and UFLC have been used in laboratories for the qualitative and qua...

  11. Sample Preparation and Extraction in Small Sample Volumes Suitable for Pediatric Clinical Studies: Challenges, Advances, and Experiences of a Bioanalytical HPLC-MS/MS Method Validation Using Enalapril and Enalaprilat

    Science.gov (United States)

    Burckhardt, Bjoern B.; Laeer, Stephanie

    2015-01-01

    In USA and Europe, medicines agencies force the development of child-appropriate medications and intend to increase the availability of information on the pediatric use. This asks for bioanalytical methods which are able to deal with small sample volumes as the trial-related blood lost is very restricted in children. Broadly used HPLC-MS/MS, being able to cope with small volumes, is susceptible to matrix effects. The latter restrains the precise drug quantification through, for example, causing signal suppression. Sophisticated sample preparation and purification utilizing solid-phase extraction was applied to reduce and control matrix effects. A scale-up from vacuum manifold to positive pressure manifold was conducted to meet the demands of high-throughput within a clinical setting. Faced challenges, advances, and experiences in solid-phase extraction are exemplarily presented on the basis of the bioanalytical method development and validation of low-volume samples (50 μL serum). Enalapril, enalaprilat, and benazepril served as sample drugs. The applied sample preparation and extraction successfully reduced the absolute and relative matrix effect to comply with international guidelines. Recoveries ranged from 77 to 104% for enalapril and from 93 to 118% for enalaprilat. The bioanalytical method comprising sample extraction by solid-phase extraction was fully validated according to FDA and EMA bioanalytical guidelines and was used in a Phase I study in 24 volunteers. PMID:25873972

  12. Sample Preparation and Extraction in Small Sample Volumes Suitable for Pediatric Clinical Studies: Challenges, Advances, and Experiences of a Bioanalytical HPLC-MS/MS Method Validation Using Enalapril and Enalaprilat.

    Science.gov (United States)

    Burckhardt, Bjoern B; Laeer, Stephanie

    2015-01-01

    In USA and Europe, medicines agencies force the development of child-appropriate medications and intend to increase the availability of information on the pediatric use. This asks for bioanalytical methods which are able to deal with small sample volumes as the trial-related blood lost is very restricted in children. Broadly used HPLC-MS/MS, being able to cope with small volumes, is susceptible to matrix effects. The latter restrains the precise drug quantification through, for example, causing signal suppression. Sophisticated sample preparation and purification utilizing solid-phase extraction was applied to reduce and control matrix effects. A scale-up from vacuum manifold to positive pressure manifold was conducted to meet the demands of high-throughput within a clinical setting. Faced challenges, advances, and experiences in solid-phase extraction are exemplarily presented on the basis of the bioanalytical method development and validation of low-volume samples (50 μL serum). Enalapril, enalaprilat, and benazepril served as sample drugs. The applied sample preparation and extraction successfully reduced the absolute and relative matrix effect to comply with international guidelines. Recoveries ranged from 77 to 104% for enalapril and from 93 to 118% for enalaprilat. The bioanalytical method comprising sample extraction by solid-phase extraction was fully validated according to FDA and EMA bioanalytical guidelines and was used in a Phase I study in 24 volunteers.

  13. Bioanalytical method development and validation for determination of metoprolol tartarate and hydrochlorothiazide using HPTLC in human plasma

    Directory of Open Access Journals (Sweden)

    Ambadas Ranganath Rote

    2013-12-01

    Full Text Available A simple, sensitive, rapid and economic chromatographic method has been developed for determination of metoprolol tartarate and hydrochlorothiazide in human plasma using paracetamol as an internal standard. The analytical technique used for method development was high-performance thin-layer chromatography. HPTLC Camag with precoated silica gel Plate 60F254 (20 cm×10 cm at 250 µm thicknesses (E. Merck, Darmstadt, Germany was used as the stationary phase. The mobile phase used consisted of chloroform: methanol: ammonia (9:1:0.5v/v/v. Densitometric analysis was carried out at a wavelength of 239 nm. The rf values for hydrochlorothiazide, paracetamol and metoprolol tartarate were 0.13±0.04, 0.28±0.05, 0.48±0.04, respectively. Plasma samples were extracted by protein precipitation with methanol. Concentration ranges of 200, 400, 600, 800, 1000, 1200 ng/mL and 2000, 4000, 6000, 8000, 10000, 12000 ng/mL of hydrochlorothiazide and metoprolol tartarate, respectively, were used with plasma for the calibration curves. The percent recovery of metoprolol tartarate and hydrochlorothiazide was found to be 77.30 and 77.02 %, respectively. The stability of metoprolol tartarate and hydrochlorothiazide in plasma were confirmed during three freeze-thaw cycles (-20 ºC on a bench for 24 hours and post-preparatively for 48 hours. The proposed method was validated statistically and proved suitable for determination of metoprolol tartarate and hydrochlorothiazide in human plasma.

  14. Quantitative bioanalytical and analytical method development of dibenzazepine derivative, carbamazepine: A review

    Directory of Open Access Journals (Sweden)

    Prasanna A. Datar

    2015-08-01

    Full Text Available Bioanalytical methods are widely used for quantitative estimation of drugs and their metabolites in physiological matrices. These methods could be applied to studies in areas of human clinical pharmacology and toxicology. The major bioanalytical services are method development, method validation and sample analysis (method application. Various methods such as GC, LC–MS/MS, HPLC, HPTLC, micellar electrokinetic chromatography, and UFLC have been used in laboratories for the qualitative and quantitative analysis of carbamazepine in biological samples throughout all phases of clinical research and quality control. The article incorporates various reported methods developed to help analysts in choosing crucial parameters for new method development of carbamazepine and its derivatives and also enumerates metabolites, and impurities reported so far. Keywords: Carbamazepine, HPLC, LC–MS/MS, HPTLC, RP-UFLC, Micellar electrokinetic chromatography

  15. Development and Validation of A Bioanalytical Method to Quantitate Enzalutamide and its Active Metabolite N-Desmethylenzalutamide in Human Plasma: Application to Clinical Management of Metastatic Castration-Resistant Prostate Cancer Patients.

    Science.gov (United States)

    Benoist, Guillemette E; van der Meulen, Eric; van Oort, Inge M; Beumer, Jan Hendrik; Somford, Diederik M; Schalken, Jack A; Burger, David M; van Erp, Nielka P

    2018-02-05

    Enzalutamide is a potent androgen-signaling receptor inhibitor and is licensed for the treatment of metastatic castration-resistant prostate cancer. N-desmethylenzalutamide is the active metabolite of enzalutamide. A method to quantitate enzalutamide and its active metabolite was developed and validated according to the European Medicine Agency (EMA) guidelines. Enzalutamide and N-desmethylenzalutamide were extracted by protein precipitation, separated on a C18 column with gradient elution and analyzed with tandem quadruple mass spectrometry in positive ion mode. A stable deuterated isotope (D6-enzalutamide) was used as an internal standard. The method was tested and stability was studied in real life patients with metastatic castration-resistant prostate cancer patients treated with enzalutamide. The calibration curve covered the range of 500-50000 ng/mL. Within- and between-day precisions were <8% and accuracies were within 108% for both enzalutamide and N-desmethylenzalutamide. Precisions for lower-limit-of-quantification level were <10% and accuracies within 116% for enzalutamide and N-desmethylenzalutamide. Enzalutamide and N-desmethylenzalutamide stability was proven for 24 hours for whole blood at ambient temperature, and 23 days for plasma at both ambient temperature and 2-8 °C. Long-term patient plasma stability was shown for 14 months at -40 °C. This bioanalytical method was successfully validated and applied to determine plasma concentrations of enzalutamide and N-desmethylenzalutamide in clinical studies and in routine patient care.

  16. Bioanalytical method development and validation of milnacipran in rat plasma by LC-MS/MS detection and its application to a pharmacokinetic study.

    Science.gov (United States)

    Kanala, Kanchanamala; T Hwisa, Nagiat; Chandu, Babu Rao; Katakam, Prakash; Khagga, Mukkanti; Challa, B R; Khagga, Bhavyasri

    2013-12-01

    A simple, sensitive and specific liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed for the quantification of milnacipran (MC) in rat plasma by using the liquid-liquid extraction method. Milnacipran-d10 (MCD10) was used as an internal standard (IS). Chromatographic separation was achieved on Zorbax SB-CN (4.6 mm×75 mm, 3.5 µm) column with an isocratic mobile phase composed of 10 mM ammonium acetate (pH 4.0) and methanol in the ratio of 25:75(v/v), at a flow-rate of 0.7 mL/min. MC and MCD10 were detected with proton adducts at m/z 247.2→230.3 and m/z 257.2→240.4 in multiple reaction monitoring (MRM) positive mode respectively. The method was validated over a linear concentration range of 1.00-400.00 ng/mL with a correlation coefficient ( r 2 )≥0.9850. This method demonstrated intra- and inter-day precision within 5.40-10.85% and 4.40-8.29% and accuracy within 97.00-104.20% and 101.64-106.23%. MC was found to be stable throughout three freeze-thaw cycles, bench top and postoperative stability studies. This method was successfully applied to a pharmacokinetic study of rats through i.v. administration.

  17. Development and validation of an ultra-performance liquid chromatography/electrospray ionization-tandem mass spectrometry bioanalytical method for quantifying clonazepam in human plasma.

    Science.gov (United States)

    Favreto, Wagner Alex Jann; Pinto, Ana Maria Pugens; Manfio, Josélia Larger; Hoss, Ivonete; Pristch, Mariely Camila; Bordignon, Solange Fátima

    2013-01-01

    A sensitive, selective, and rapid ultra-performance LC (UPLC)/MSIMS method was validated for the confirmation and quantification of clonazepam in human plasma. The analyte was extracted from human plasma with diethyl ether, reaching an average recovery of 64.02 and 66.48% for clonazepam and the internal standard, respectively. The separation was performed on a Waters ACQUITY UPLC BEH C18 column (50 x 2.1 mm id, 1.7 microm particle size) with gradient elution at a flow rate of 0.25 mL/min using a 0.5% formic acid solution (mobile phase A) and acetonitrile-methanol-formic acid (75+25 + 0.5, v/v/v; mobile phase B). Detection was performed on a triple-quadruple tandem mass spectrometer in the multiple reaction monitoring mode via electrospray ionization. Linear calibration curves were obtained in the concentration range of 0.3-50.0 ng/mL, with an LOQ of 0.3 ng/mL. The intraday and interday precision (CV) values were below 10%, and accuracy (relative error) ranged from -2.6 to 6.6% at all QC levels. The suggested method was successfully applied for the determination of clonazepam in human plasma in a bioequivalence study.

  18. Multiplex bioanalytical methods for food and environmental monitoreing

    NARCIS (Netherlands)

    Rebe, S.; Haasnoot, W.

    2011-01-01

    Recent advances in miniaturization of analytical systems and newly emerging technologies offer platforms with greater automation and multiplexing capabilities than traditional biological binding assays. Multiplexed bioanalytical techniques provide control agencies and food industries with new

  19. A fully validated bioanalytical method using an UHPLC-MS/MS system for quantification of DNA and RNA oxidative stress biomarkers.

    Science.gov (United States)

    Cervinkova, Barbora; Krcmova, Lenka Kujovska; Sestakova, Veronika; Solichova, Dagmar; Solich, Petr

    2017-05-01

    A new, rapid and effective ultra-high-performance liquid chromatography method with mass spectrometry detection is described for the separation and quantification of 8-hydroxy-2-deoxyguanosine, 8-hydroxyguanosine and creatinine in human urine. The present study uses an isotope-labelled internal standard ([ 15 N] 5 -8-hydroxy-2-deoxyguanosine), a BIO core-shell stationary phase and an isocratic elution of methanol and water. Sample preparation of human urine was performed by solid-phase extraction (SPE) on Oasis HLB cartridges with methanol/water 50:50 (v/v) elution. Extraction recoveries ranged from 98.1% to 109.2%. Biological extracts showed high short-term stability. Several aspects of this procedure make it suitable for both clinical and research purposes: a short elution time of less than 3.2 min, an intra-day precision of 2.5-8.9%, an inter-day precision of 3.4-8.7% and low limits of quantification (27.7 nM for 8-hydroxyguanosine, 6.0 nM for 8-hydroxy-2-deoxyguanosine). Finally, simultaneous analysis of DNA and RNA oxidative stress biomarkers is a useful tool for monitoring disease progression in neurodegenerative disorders and cancer. Graphical abstract UHPLC-MS/MS analysis of DNA and RNA oxidative stress biomarkers.

  20. Aging of biological matrices and its effect on bioanalytical method performance

    NARCIS (Netherlands)

    van de Merbel, Nico C.; de Vries, R.

    2013-01-01

    Apart from the well-known matrix effects that can occur in ESI LC-MS, biological matrices may have other effects influencing the quantitative reliability of bioanalytical methods. In this paper, six case studies are presented that show the effect that aging, that is the change in properties and

  1. The quest for assay robustness across the life cycle of a bioanalytical method.

    Science.gov (United States)

    White, Stephen; Dunn, John; Summerfield, Scott

    2015-01-01

    White has been an analytical chemist for 28 years, with a range of knowledge and experience across multiple disciplines including pharmaceuticals, foodstuffs, environmental and forensic analysis. Steve works within the regulated bioanalytical group at GSK supporting both preclinical and clinical bioanalysis. His responsibilities have included leadership of bioanalytical, dose formulation and sample management teams as well as assisting with the set up of the Anti-Doping Testing Laboratory for the London 2012 Olympics. In his current role, Steve is part of the UK bioanalytical leadership team with a focus on regulatory & compliance issues. Steve is the small molecule rep for GSK within the European Bioanalysis Forum (EBF), a member of the EBF Steering Committee and also contributed to the Global Bioanalysis Consortium S2 team. The successful validation or qualification of an assay plus incurred sample reproducibility gives the bioanalyst confidence of assay suitability. However, these elements alone do not give the full picture of how reliable an assay may be during routine production use for analysis of unknown study samples. The robustness of an assay can be understood by applying key performance indicators to monitor assay performance pre- and post-transfer between laboratories, plus a cross-validation step during assay transfer. The measurement of assay robustness (beyond the context of cross-validation) should not be considered as yet another regulatory layer, but more as a means for the bioanalyst to better understand an individual assay within a large portfolio, when used for its intended purpose.

  2. A Simple HPLC Bioanalytical Method for the Determination of ...

    African Journals Online (AJOL)

    Purpose: To develop a simple, accurate, and precise high performance chromatography (HPLC) method with spectrophotometric detection for the determination of doxorubicin hydrochloride in rat plasma. Methods: Doxorubicin hydrochloride and daunorubicin hydrochloride (internal standard, IS) were separated on a C18 ...

  3. Impact of Chiral Bioanalytical Methods on the Bioequivalence of Ibuprofen Products Containing Ibuprofen Lysinate and Ibuprofen Base.

    Science.gov (United States)

    García-Arieta, Alfredo; Ferrero-Cafiero, Juan Manuel; Puntes, Montse; Gich, Ignasi; Morales-Alcelay, Susana; Tarré, Maite; Font, Xavier; Antonijoan, Rosa Maria

    2016-05-01

    The purpose was to assess the impact of the use of a chiral bioanalytical method on the conclusions of a bioequivalence study that compared two ibuprofen suspensions with different rates of absorption. A comparison of the conclusion of bioequivalence between a chiral method and an achiral approach was made. Plasma concentrations of R-ibuprofen and S-ibuprofen were determined using a chiral bioanalytical method; bioequivalence was tested for R-ibuprofen and for S-ibuprofen separately and for the sum of both enantiomers as an approach for an achiral bioanalytical method. The 90% confidence interval (90% CI) that would have been obtained with an achiral bioanalytical method (90% CI: Cmax: 117.69-134.46; AUC0 (t) : 104.75-114.45) would have precluded the conclusion of bioequivalence. This conclusion cannot be generalized to the active enantiomer (90% CI: Cmax : 103.36-118.38; AUC0 (t) : 96.52-103.12), for which bioequivalence can be concluded, and/or the distomer (90% CI: Cmax : 132.97-151.33; AUC0 (t) : 115.91-135.77) for which a larger difference was observed. Chiral bioanalytical methods should be required when 1) the enantiomers exhibit different pharmacodynamics and 2) the exposure (AUC or Cmax ) ratio of enantiomers is modified by a difference in the rate of absorption. Furthermore, the bioequivalence conclusion should be based on all enantiomers, since the distomer(s) might not be completely inert, in contrast to what is required in the current regulatory guidelines. In those cases where it is unknown if the ratio between enantiomers is modified by changing the rate of absorption, chiral bioanalytical methods should be employed unless enantiomers exhibit the same pharmacodynamics. Chirality 28:429-433, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  4. Development and validation of a bioanalytical method for the simultaneous determination of heroin, its main metabolites, naloxone and naltrexone by LC-MS/MS in human plasma samples: Application to a clinical trial of oral administration of a heroin/naloxone formulation.

    Science.gov (United States)

    Moreno-Vicente, Raquel; Fernández-Nieva, Zuriñe; Navarro, Arantza; Gascón-Crespí, Irene; Farré-Albaladejo, Magí; Igartua, Manuela; Hernández, Rosa María; Pedraz, José Luis

    2015-10-10

    A bioanalytical method using high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) was developed and validated for simultaneous quantification of heroin, its main metabolites and naloxone. In addition, naltrexone was detected qualitatively. This method was used to analyse human plasma samples from a clinical trial after oral administration of a heroin/naloxone formulation in healthy volunteers. O-methylcodeine was used as an internal standard. Samples were kept in an ice-bath during their processing to minimize the degradation of heroin. A short methodology based on protein precipitation with methanol was used for sample preparation. After protein precipitation, only the addition of a formic acid solution was needed to elute heroin, 6-monoacetylmorphine, morphine, naloxone and naltrexone. Morphine metabolites were evaporated to dryness and reconstituted in a formic acid solution. Chromatographic separation was achieved at 35 °C on an X-Bridge Phenyl column (150 × 4.6 mm, 5 μm) using a gradient elution with a mobile phase of ammonium formate buffer at pH 3.0 and formic acid in acetonitrile. The run time was 8 min. The analytes were monitored using a triple quadrupole mass spectrometer with positive electrospray ionization (ESI+) in multiple reaction monitoring (MRM) mode. The method was found to be linear in a concentration range of 10-2000 ng/mL for M3G and 10-1000 ng/mL for the rest of compounds. Quality controls showed accurate values between -3.6% and 4.0% and intra- and inter-day precisions were below 11.5% for all analytes. The overall recoveries were approximately 100% for all analytes including the internal standard. A rapid, specific, precise and simple method was developed for the determination of heroin, its metabolites, naloxone and naltrexone in human plasma. This method was successfully applied to a clinical trial in 12 healthy volunteers. Copyright © 2015 Elsevier B.V. All rights reserved.

  5. Pharmacokinetic-pharmacodynamic correlation of imipenem in pediatric burn patients using a bioanalytical liquid chromatographic method

    Directory of Open Access Journals (Sweden)

    Silvia Regina Cavani Jorge Santos

    2015-06-01

    Full Text Available A bioanalytical method was developed and applied to quantify the free imipenem concentrations for pharmacokinetics and PK/PD correlation studies of the dose adjustments required to maintain antimicrobial effectiveness in pediatric burn patients. A reverse-phase Supelcosil LC18 column (250 x 4.6 mm 5 micra, binary mobile phase consisting of 0.01 M, pH 7.0 phosphate buffer and acetonitrile (99:1, v/v, flow rate of 0.8 mL/min, was applied. The method showed good absolute recovery (above 90%, good linearity (0.25-100.0 µg/mL, r2=0.999, good sensitivity (LLOQ: 0.25 µg/mL; LLOD: 0.12 µg/mL and acceptable stability. Inter/intraday precision values were 7.3/5.9%, and mean accuracy was 92.9%. A bioanalytical method was applied to quantify free drug concentrations in children with burns. Six pediatric burn patients (median 7.0 years old, 27.5 kg, normal renal function, and 33% total burn surface area were prospectively investigated; inhalation injuries were present in 4/6 (67% of the patients. Plasma monitoring and PK assessments were performed using a serial blood sample collection for each set, totaling 10 sets. The PK/PD target attained (40%T>MIC for each minimum inhibitory concentration (MIC: 0.5, 1.0, 2.0, 4.0 mg/L occurred at a percentage higher than 80% of the sets investigated and 100% after dose adjustment. In conclusion, the purification of plasma samples using an ultrafiltration technique followed by quantification of imipenem plasma measurements using the LC method is quite simple, useful, and requires small volumes for blood sampling. In addition, a small amount of plasma (0.25 mL is needed to guarantee drug effectiveness in pediatric burn patients. There is also a low risk of neurotoxicity, which is important because pharmacokinetics are unpredictable in these critical patients with severe hospital infection. Finally, the PK/PD target was attained for imipenem in the control of sepsis in pediatric patients with burns.

  6. A Critical Review of Properties of Modafinil and Analytical, Bioanalytical Methods for its Determination.

    Science.gov (United States)

    Ramachandra, B

    2016-11-01

    Modafinil is a synthetic molecule used for the treatment of narcolepsy. Narcolepsy is a neurological disorder, due to which people experience frequent excessive daytime sleepiness (EDS). Nevertheless, there are some concerns about modafnil quality control. The modafinil enantiomers are both biologically active. However, it has been reported that the pharmacological properties of the both enantiomers are different and that the S-enantiomer is eliminated three times faster than the R-enantiomer. Therefore, most of the pharmaceutical companies have shifted to produce armodafinil (R-enantiomer) instead of the racemate. This article discusses about the critical review of the literature, the impact of the use of modafinil in the treatment of narcolepsy patients and other diseases, its physicochemical properties, toxicological properties, synthetic methods, analytical and bioanalytical methods and challenges that remain in order to ensure the quality. This article mainly focused on review of process related impurities, enantiomeric separation, metabolites of modafinil in various biofluids and pharmaceutical formulations using HPLC, LC-MS, GC-MS, CE, HPTLC and spectrophotometric methods.

  7. Synergic development of pharmacokinetics and bioanalytical methods as support of pharmaceutical research.

    Science.gov (United States)

    Marzo, M; Ciccarelli, R; Di Iorio, P; Giuliani, P; Caciagli, F; Marzo, A

    2016-06-01

    The development of pharmacokinetics led this science to achieve a relevant role in the investigation of new chemical entities for therapeutic application, and has allowed a series of new useful realizations of out of patent drugs like prolonged release and delayed release formulations, therapeutic delivery system (TDS) for drugs to be active in systemic circulation avoiding the first pass effect, orodispersible and effervescent formulations, intramuscular and subcutaneous depot formulations acting over a long period, oral inhalatory systems, and drug association at fixed dose. The above applications had pharmacokinetics as protagonist and have required the support from bioanalytical methods to assay drug concentrations, even in pg·mL(-1) of plasma, that really have paralleled the synergic development of pharmacokinetics.The complexity of the above realizations required specific guidelines from the regulatory authorities, mainly the US FDA and EU EMA, which have normalized and, in most cases, simplified the above applications admitting some waivers of in vivo bioequivalence.However, this review highlights some critical points, not yet focused on by operating guidelines, which need to be clarified by regulatory authorities. One of the most relevant issues is about the planning and conducting bioavailability and bioequivalence trials with endogenous substances, that possess own homeostatic equilibria with fluctuations, in some cases with specific rhythms, like melatonin and female sex hormones. The baseline subtraction required by guidelines to define the net contribute to the exogenous absorbed drug in most cases is a non-solvable problem. © The Author(s) 2015.

  8. Bioanalytical method for in vitro metabolism study of repaglinide using 96-blade thin-film solid-phase microextraction and LC-MS/MS.

    Science.gov (United States)

    Simões, Rodrigo Almeida; Bonato, Pierina Sueli; Mirnaghi, Fatemeh S; Bojko, Barbara; Pawliszyn, Janusz

    2015-01-01

    A high-throughput bioanalytical method using 96-blade thin film microextraction (TFME) and LC-MS/MS for the analysis of repaglinide (RPG) and two of its main metabolites was developed and used for an in vitro metabolism study. The target analytes were extracted from human microsomal medium by a 96-blade-TFME system employing the low-cost prototype 'SPME multi-sampler' using C18 coating. Method validation showed recoveries around 90% for all analytes and was linear over the concentration range of 2-1000 ng ml(-1) for RPG and of 2-500 ng ml(-1) for each RPG metabolite. The method was applied to an in vitro metabolism study of RPG employing human liver microsomes and proved to be very useful for this purpose.

  9. Outsourcing bioanalytical services at Janssen Research and Development: the sequel anno 2017.

    Science.gov (United States)

    Dillen, Lieve; Verhaeghe, Tom

    2017-08-01

    The strategy of outsourcing bioanalytical services at Janssen has been evolving over the last years and an update will be given on the recent changes in our processes. In 2016, all internal GLP-related activities were phased out and this decision lead to the re-orientation of the in-house bioanalytical activities. As a consequence, in-depth experience with the validated bioanalytical assays for new drug candidates is currently gained together with the external partner, since development and validation of the assay and execution of GLP preclinical studies are now transferred to the CRO. The evolution to externalize more bioanalytical support has created opportunities to build even stronger partnerships with the CROs and to refocus internal resources. Case studies are presented illustrating challenges encountered during method development and validation at preferred partners when limited internal experience is obtained or with introduction of new technology.

  10. Review of the bioanalytical methods for the determination of methotrexate and its metabolites in in vitro, preclinical and clinical studies

    DEFF Research Database (Denmark)

    Patel, Harilal; Giri, Poonam; Ghoghari, Ashok

    2017-01-01

    Methotrexate is an old drug that has found use in several therapeutic areas, such as cancer to treat various malignancies, rheumatoid arthtritis and inflammatory bowel disease. Owing to its structural properties of possessing two carboxylic acid groups and having low native fluorescence, it has...... provided technical challenges for development of bioanalytical methods. Also, in vivo metabolism leading to circulatory metabolites such as 7-hydroxymethotrexate and 2,4-diamino N(10) -methylpteroic acid, as well as the formation of polyglutamate metabolites intracellularly have added further complexity...

  11. Biosensors for environmental monitoring of aquatic systems. Bioanalytical and chemical methods for endocrine disruptors

    Energy Technology Data Exchange (ETDEWEB)

    Barcelo, Damia [IDAEA-CSIC, Barcelona (Spain). Dept. of Environmental Chemistry; Girona Univ. (ES). Catalan Inst. for Water Research (ICRA); Hansen, Peter-Diedrich (eds.) [Berlin Inst. of Technology, Berlin (Germany). Dept. of Ecotoxicology

    2009-07-01

    There is an increasing need for effective methods of estimating the risks caused by the large number of pollutants released into the environment by human activities. This volume provides an overview of biosensors as a key tool for the environmental monitoring of aquatic systems. Biosensor technology is based on a specific biological recognition element in combination with a transducer for signal processing. In particular, the detection and identification of endocrine-disrupting compounds and other toxins in wastewater are treated in detail. Biosensors are presented as a practical alternative or supplement to traditional chromatographic techniques. Emphasis is also placed on the validation of the applied technology and its application to real-world environmental samples. (orig.)

  12. Development and validation of a spectroscopic method for the ...

    African Journals Online (AJOL)

    ) as the solvent system. All solutions were analyzed for absorbance spectrophotometrically at 205 and 249 ... fluoromertric method [10], micellar electrokinetic chromatographic method [11], bioanalytical method [12], photochemical reaction [13] ...

  13. Bioanalytical method for the estimation of co-administered esomeprazole, leflunomide and ibuprofen in human plasma and in pharmaceutical dosage forms using micellar liquid chromatography.

    Science.gov (United States)

    Talaat, Wael

    2017-05-01

    The present study represents a connection between basic science and clinical applied science through providing a bioanalytical method for the analysis of certain co-administered drugs used for the treatment of rheumatoid arthritis. The studied drugs are esomeprazole, leflunomide and ibuprofen. The proposed bioanalytical method is a simple reversed phase high performance liquid chromatographic method using micellar mobile phase. The method is conducted using a Shim-pack VP-ODS (150 mm × 4.6 mm ID) stainless steel column at ambient temperature with ultraviolet detection at 285 nm. The micellar mobile phase consisted of 0.1 m sodium dodecyl sulfate, 10% n-propanol, 0.3% triethylamine in 0.02 m orthophosphoric acid (pH 3.5) and is pumped at a flow rate of 1.0 mL/min. The calibration curve was rectilinear over the concentration range of 0.1-5.0, 0.5-10.0 and 1.0-20.0 μg/mL for esomeprazole, leflunomide and ibuprofen respectively. The proposed method was successfully applied to the analysis of these drugs in dosage forms. The method is extended to the in-vitro, in-vivo determination of these drugs in spiked and real human plasma samples. Copyright © 2016 John Wiley & Sons, Ltd.

  14. Bioanalytical methods for the determination of cocaine and metabolites in human biological samples.

    Science.gov (United States)

    Barroso, M; Gallardo, E; Queiroz, J A

    2009-08-01

    Determination of cocaine and its metabolites in biological specimens is of great importance, not only in clinical and forensic toxicology, but also in workplace drug testing. These compounds are normally screened for using sensitive immunological methods. However, screening methods are unspecific and, therefore, the posterior confirmation of presumably positive samples by a specific technique is mandatory. Although GC-MS-based techniques are still the most commonly used for confirmation purposes of cocaine and its metabolites in biological specimens, the advent of LC-MS and LC-MS/MS has enabled the detection of even lower amounts of these drugs, which assumes particular importance when sample volume available is small, as frequently occurs with oral fluid. This paper will review recently-published papers that describe procedures for detection of cocaine and metabolites, not only in the most commonly used specimens, such as blood and urine, but also in other 'alternative' matrices (e.g., oral fluid and hair) with a special focus on sample preparation and chromatographic analysis.

  15. Bioanalytical methods for determination of tamoxifen and its phase I metabolites: A review

    International Nuclear Information System (INIS)

    Teunissen, S.F.; Rosing, H.; Schinkel, A.H.; Schellens, J.H.M.; Beijnen, J.H.

    2010-01-01

    The selective estrogen receptor modulator tamoxifen is used in the treatment of early and advanced breast cancer and in selected cases for breast cancer prevention in high-risk subjects. The cytochrome P450 enzyme system and flavin-containing monooxygenase are responsible for the extensive metabolism of tamoxifen into several phase I metabolites that vary in toxicity and potencies towards estrogen receptor (ER) alpha and ER beta. An extensive overview of publications on the determination of tamoxifen and its phase I metabolites in biological samples is presented. In these publications techniques were used such as capillary electrophoresis, liquid, gas and thin layer chromatography coupled with various detection techniques (mass spectrometry, ultraviolet or fluorescence detection, liquid scintillation counting and nuclear magnetic resonance spectroscopy). A trend is seen towards the use of liquid chromatography coupled to mass spectrometry (LC-MS). State-of-the-art LC-MS equipment allowed for identification of unknown metabolites and quantification of known metabolites reaching lower limit of quantification levels in the sub pg mL -1 range. Although tamoxifen is also metabolized into phase II metabolites, the number of publications reporting on phase II metabolism of tamoxifen is scarce. Therefore the focus of this review is on phase I metabolites of tamoxifen. We conclude that in the past decades tamoxifen metabolism has been studied extensively and numerous metabolites have been identified. Assays have been developed for both the identification and quantification of tamoxifen and its metabolites in an array of biological samples. This review can be used as a resource for method transfer and development of analytical methods used to support pharmacokinetic and pharmacodynamic studies of tamoxifen and its phase I metabolites.

  16. Bioanalytical methods for determination of tamoxifen and its phase I metabolites: A review

    Energy Technology Data Exchange (ETDEWEB)

    Teunissen, S.F., E-mail: Bas.Teunissen@slz.nl [Department of Pharmacy and Pharmacology, Slotervaart Hospital, The Netherlands Cancer Institute, Louwesweg 6, 1066 EC Amsterdam (Netherlands); Rosing, H. [Department of Pharmacy and Pharmacology, Slotervaart Hospital, The Netherlands Cancer Institute, Louwesweg 6, 1066 EC Amsterdam (Netherlands); Schinkel, A.H. [Division of Molecular Biology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX, Amsterdam (Netherlands); Schellens, J.H.M. [Department of Medical Oncology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX, Amsterdam (Netherlands); Department of Pharmaceutical Sciences, Science Faculty, Utrecht University, Utrecht (Netherlands); Beijnen, J.H. [Department of Pharmacy and Pharmacology, Slotervaart Hospital, The Netherlands Cancer Institute, Louwesweg 6, 1066 EC Amsterdam (Netherlands); Department of Pharmaceutical Sciences, Science Faculty, Utrecht University, Utrecht (Netherlands)

    2010-12-17

    The selective estrogen receptor modulator tamoxifen is used in the treatment of early and advanced breast cancer and in selected cases for breast cancer prevention in high-risk subjects. The cytochrome P450 enzyme system and flavin-containing monooxygenase are responsible for the extensive metabolism of tamoxifen into several phase I metabolites that vary in toxicity and potencies towards estrogen receptor (ER) alpha and ER beta. An extensive overview of publications on the determination of tamoxifen and its phase I metabolites in biological samples is presented. In these publications techniques were used such as capillary electrophoresis, liquid, gas and thin layer chromatography coupled with various detection techniques (mass spectrometry, ultraviolet or fluorescence detection, liquid scintillation counting and nuclear magnetic resonance spectroscopy). A trend is seen towards the use of liquid chromatography coupled to mass spectrometry (LC-MS). State-of-the-art LC-MS equipment allowed for identification of unknown metabolites and quantification of known metabolites reaching lower limit of quantification levels in the sub pg mL{sup -1} range. Although tamoxifen is also metabolized into phase II metabolites, the number of publications reporting on phase II metabolism of tamoxifen is scarce. Therefore the focus of this review is on phase I metabolites of tamoxifen. We conclude that in the past decades tamoxifen metabolism has been studied extensively and numerous metabolites have been identified. Assays have been developed for both the identification and quantification of tamoxifen and its metabolites in an array of biological samples. This review can be used as a resource for method transfer and development of analytical methods used to support pharmacokinetic and pharmacodynamic studies of tamoxifen and its phase I metabolites.

  17. The international validation of bio- and chemical-anlaytical screening methods for dioxins and dioxin-like PCBs: the DIFFERENCE project rounds 1 and 2

    NARCIS (Netherlands)

    Loco, van J.; Leeuwen, van S.P.J.; Roos, P.; Carbonnelle, S.; Boer, de J.; Goeyens, L.; Beernaert, H.

    2004-01-01

    The European research project DIFFERENCE is focussed on the development, optimisation and validation of screening methods for dioxin analysis, including bio-analytical and chemical techniques (CALUX, GC-LRMS/MS, GC x GC-ECD) and on the optimisation and validation of new extraction and clean-up

  18. A novel liquid chromatography/tandem mass spectrometry (LC-MS/MS) based bioanalytical method for quantification of ethyl esters of Eicosapentaenoic acid (EPA) and Docosahexaenoic acid (DHA) and its application in pharmacokinetic study.

    Science.gov (United States)

    Viswanathan, Sekarbabu; Verma, P R P; Ganesan, Muniyandithevar; Manivannan, Jeganathan

    2017-07-15

    Omega-3 fatty acids are clinically useful and the two marine omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are prevalent in fish and fish oils. Omega-3 fatty acid formulations should undergo a rigorous regulatory step in order to obtain United States Food and Drug Administration (USFDA) approval as prescription drug. In connection with that, despite quantifying EPA and DHA fatty acids, there is a need for quantifying the level of ethyl esters of them in biological samples. In this study, we make use of reverse phase high performance liquid chromatography coupled with mass spectrometry (RP-HPLC-MS)technique for the method development. Here, we have developed a novel multiple reaction monitoring method along with optimized parameters for quantification of EPA and DHA as ethyl esters. Additionally, we attempted to validate the bio-analytical method by conducting the sensitivity, selectivity, precision accuracy batch, carryover test and matrix stability experiments. Furthermore, we also implemented our validated method for evaluation of pharmacokinetics of omega fatty acid ethyl ester formulations. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. [Bioanalytics in medicinal chemistry: from assay development to evolutive drug design].

    Science.gov (United States)

    Jose, J

    2009-11-01

    During the last decade, the focus of bioanalytics shifted from the mere analysis of biomacromolecules to the application of proteins and nucleic acids for analytical purposes, e.g. accessing the biological role of cellular constituents, target identification and validation, quantification of receptor-ligand interactions and others. The increasing impact of combining biomacromolecules with standard analytic devices can be exemplified by the central role of DNA and protein micro-arrays in the fields of genomics, proteomics, transcriptomics or pharmacogenomics. Medicinal chemistry is considered as the scientific discipline concerned with the discovery, design, identification, and preparation of biologically active compounds and the interpretation of their mode of action at the molecular level and their metabolites. From this definition it is evident that bioanalytical tools put into service of medicinal chemistry needs can contribute substantially to progress in drug discovery, design and identification, especially in cases when these tools are well-adapted for miniaturisation and automation to enable high throughput screening. Many successful examples of combining biomacromolecules with standard instrumental analytics indicate that the former role of biochemical testing in medicinal chemistry is more and more replaced by what we call molecular bioanalytics. In recent research, we showed how molecular biology methods and whole cell approaches can be integrated into new bioanalytical tools of complex assembly and how these tools are applicable for drug discovery, drug synthesis and high throughput screening. This is exemplified by the evolutive development of enzyme inhibitors for targets in chronic inflammatory diseases (cathepsin G) or cancer (CK2, hyaluronidase).

  20. Validating dialect comparison methods

    NARCIS (Netherlands)

    Nerbonne, J.; Kleiweg, P.; Gaul, W; Ritter, G

    2002-01-01

    The range of dialectometric methods suggests the need for validation work. We propose a gold standard, based on the consensual classification of a well-studied area. Fidelity to the gold standard is assessed via matrix overlap measures (Rand and Fowlkes/Mallows). Word-based techniques in which

  1. Bioanalytical LC-MS/MS of protein-based biopharmaceuticals

    NARCIS (Netherlands)

    Broek, I. van den; Niessen, W.M.A.; Dongen, W.D. van

    2013-01-01

    Biotechnology increasingly delivers highly promising protein-based biopharmaceutical candidates to the drug development funnel. For successful biopharmaceutical drug development, reliable bioanalytical methods enabling quantification of drugs in biological fluids (plasma, urine, tissue, etc.) are

  2. 78 FR 56718 - Draft Guidance for Industry on Bioanalytical Method Validation; Availability

    Science.gov (United States)

    2013-09-13

    ...), and biologics license applications (BLAs) for therapeutic biologics regulated by the Center for Drug... are of critical importance to the interpretation of the study outcomes. The draft guidance reflects.... It does not create or confer any rights for or on any person and does not operate to bind FDA or the...

  3. Method development and validation for determination of antihemolytic activity of eculizumab (Soliris

    Directory of Open Access Journals (Sweden)

    E. Yu. Prudnikova

    2016-01-01

    Full Text Available Bioanalytical methods are applied at the development and test of drugs as well as at the step of pharmaceutic products issue. Drugs and excipients quality estimation is made by means of precise and reproducible methods. Accuracy and reproducibility of a method is established during validation which is obligatory for medicine registration. The principal task of method validation is experimental evidence of its suitability for the objectives to be achieved. Validation of bioanalytical methods is one of the elements of the whole medicine production validation [1, 2].The aim of research: to validate a method for determination of specific anti-hemolytic activity of eculizumab developed in LCC “IBC Generium”.Materials and methods: eculizumab, antibody-sensitized chicken erythrocytes, complement-containing human serum.Results. We demonstrated the specificity of the method and its correspondence to criteria of accuracy (103.0±1.4%, robustness (CV – 11.5%, repeatability (CV – (4.9±0.9%, reproducibility (CV – (3.5±0.4%, and linearity (k -1.0275; R2 – 0.9975 during validation. The system validity (equipment, materials, analytical operations and analyzed samples was confirmed for true results obtaining during validation.Results discussion. Experimental evidence of suitability of the method for eculizumab specific activity assessment was obtained in course of validation. The simplicity of the method allows obtaining accurate results in other laboratories. The developed method can be used not only for specific activity of Soliris determination but also for other pharmaceutical substances and drugs based on antibodies specific to human complement C5.

  4. Validation Process Methods

    Energy Technology Data Exchange (ETDEWEB)

    Lewis, John E. [National Renewable Energy Lab. (NREL), Golden, CO (United States); English, Christine M. [National Renewable Energy Lab. (NREL), Golden, CO (United States); Gesick, Joshua C. [National Renewable Energy Lab. (NREL), Golden, CO (United States); Mukkamala, Saikrishna [National Renewable Energy Lab. (NREL), Golden, CO (United States)

    2018-01-04

    This report documents the validation process as applied to projects awarded through Funding Opportunity Announcements (FOAs) within the U.S. Department of Energy Bioenergy Technologies Office (DOE-BETO). It describes the procedures used to protect and verify project data, as well as the systematic framework used to evaluate and track performance metrics throughout the life of the project. This report also describes the procedures used to validate the proposed process design, cost data, analysis methodologies, and supporting documentation provided by the recipients.

  5. Development and Validation of Acyclovir HPLC External Standard Method in Human Plasma: Application to Pharmacokinetic Studies

    Directory of Open Access Journals (Sweden)

    Selvadurai Muralidharan

    2014-01-01

    Full Text Available A simple, rapid, and selective RP-HPLC method was developed for the estimation of acyclovir in human plasma. The method involves a simple protein precipitation technique. Chromatographic separation was carried out on a reverse phase C18 column using mixture of 5 mM ammonium acetate (pH 4.0 and acetonitrile (40 : 60, v/v at a flow rate of 1.0 mL/min with UV detection at 290 nm. The retention time of acyclovir was 4.12 minutes. The method was validated and found to be linear in the range of 25.0–150.0 ng/mL. Validation studies were achieved by using the fundamental parameters, including accuracy, precision, selectivity, sensitivity, linearity and range, stability studies, limit of detection (LOD, and limit of quantitation (LOQ. It shows recovery at 91.0% which is more precise and accurate compared to the other method. These results indicated that the bioanalytical method was linear, precise, and accurate. The new bioanalytical method was successfully applied to a pharmacokinetic linearity study in human plasma.

  6. Simple and Selective HPLC-UV/Vis Bioanalytical Method to Determine Aluminum Phthalocyanine Chloride in Skin Permeation Studies

    Directory of Open Access Journals (Sweden)

    Thaiene Avila Reis

    2018-01-01

    Full Text Available Considering the feasibility of the aluminum phthalocyanine chloride (AlPcCl application in the topical photodynamic therapy of cutaneous tumors and the lack of HPLC methods capable of supporting skin permeation experiments using this compound, the aim of this study was to obtain a simple and selective chromatographic method for AlPcCl determination in skin matrices. A HPLC-UV/Vis method was developed using a normal-phase column operating at 30°C, an isocratic mobile phase of methanol : phosphoric acid (0.01 M at 1.5 mL/min, and detection at 670 nm. The method exhibited (i selectivity against various contaminants found in the different skin layers, (ii high drug extraction capacity from the hair follicle (>70% and remaining skin (>80%, and (iii low limits of detection and of quantification (0.03 and 0.09 μg/mL, resp.. The method was also linear in the range from 0.1 to 5.0 µg/mL (r = 0.9994 and demonstrated robustness with regard to experimental chromatographic parameters according to a factorial design. Lastly, the developed method was successfully tested in in vitro skin permeation studies of AlPcCl, proving its effectiveness in the development of pharmaceutical delivery systems containing this drug for topical photodynamic therapy of skin cancers.

  7. Accelerator mass spectrometry as a bioanalytical tool for nutritional research

    Energy Technology Data Exchange (ETDEWEB)

    Vogel, J.S.; Turteltaub, K.W.

    1997-09-01

    Accelerator Mass Spectrometry is a mass spectrometric method of detecting long-lived radioisotopes without regard to their decay products or half-life. The technique is normally applied to geochronology, but recently has been developed for bioanalytical tracing. AMS detects isotope concentrations to parts per quadrillion, quantifying labeled biochemicals to attomole levels in milligram- sized samples. Its advantages over non-isotopeic and stable isotope labeling methods are reviewed and examples of analytical integrity, sensitivity, specificity, and applicability are provided.

  8. BIOANALYTICAL STANDARDIZING FOR SEROLOGICAL DIAGNOSTIC MEDICAL DEVICES

    Directory of Open Access Journals (Sweden)

    A. Yu. Galkin

    2015-04-01

    Full Text Available In article we analyzed national and international regulations concerning the quality and safety of medical devices for in vitro diagnostics. We discussed the possibility of a partial application of the recommendations of the State Pharmacopoeia of Ukraine to this type of product. The main guiding regulatory documents establishing requirements for quality and safety tools for the serological diagnosis products are The technical regulation on medical devices for the diagnosis in vitro, DSTU ISO 13485 “Medical devices. Quality management system. Regulatory requirements”, and DSTU ISO/IEC 17025 “General requirements for the competence of testing and calibration laboratories”. Similar requirements of the State Pharmacopoeia of Ukraine which are used for drug standardization can not be directly applied to the medical devises for in vitro diagnostics due to a number of features, namely, the serological diagnosis products pre-designed to determine the unknown concentration of a particular analyte in a biological material, the diagnostic kits has to include the control samples (internal standard systems that need to be calibrated. It was determined following parameters of bioanalytical standardization and validation characterization for of qualitative (semi quantitative test-kits for serological diagnosis: precision (convergence, intralaboratory precision and reproducibility, diagnostic and analytical specificity, diagnostic sensitivity. It’s necessary to inspect additional parameters for quantitative test-kits such as accuracy (precision, linearity, analytical sensitivity and range.

  9. Method development and validations: characterization of critical ...

    African Journals Online (AJOL)

    Method development and validations: characterization of critical elements in the development of pharmaceuticals. ... International Journal of Health Research ... Although a thorough validation cannot rule out all potential problems, the process of method development and validation should address the most common ones.

  10. Acceptability criteria for linear dependence in validating UV-spectrophotometric methods of quantitative determination in forensic and toxicological analysis

    Directory of Open Access Journals (Sweden)

    L. Yu. Klimenko

    2014-08-01

    Full Text Available Introduction. This article is the result of authors’ research in the field of development of the approaches to validation of quantitative determination methods for purposes of forensic and toxicological analysis and devoted to the problem of acceptability criteria formation for validation parameter «linearity/calibration model». The aim of research. The purpose of this paper is to analyse the present approaches to acceptability estimation of the calibration model chosen for method description according to the requirements of the international guidances, to form the own approaches to acceptability estimation of the linear dependence when carrying out the validation of UV-spectrophotometric methods of quantitative determination for forensic and toxicological analysis. Materials and methods. UV-spectrophotometric method of doxylamine quantitative determination in blood. Results. The approaches to acceptability estimation of calibration models when carrying out the validation of bioanalytical methods is stated in international papers, namely «Guidance for Industry: Bioanalytical method validation» (U.S. FDA, 2001, «Standard Practices for Method Validation in Forensic Toxicology» (SWGTOX, 2012, «Guidance for the Validation of Analytical Methodology and Calibration of Equipment used for Testing of Illicit Drugs in Seized Materials and Biological Specimens» (UNODC, 2009 and «Guideline on validation of bioanalytical methods» (ЕМА, 2011 have been analysed. It has been suggested to be guided by domestic developments in the field of validation of analysis methods for medicines and, particularly, by the approaches to validation methods in the variant of the calibration curve method for forming the acceptability criteria of the obtained linear dependences when carrying out the validation of UV-spectrophotometric methods of quantitative determination for forensic and toxicological analysis. The choice of the method of calibration curve is

  11. High-throughput screening assay used in pharmacognosy: Selection, optimization and validation of methods of enzymatic inhibition by UV-visible spectrophotometry

    Directory of Open Access Journals (Sweden)

    Graciela Granados-Guzmán

    2014-02-01

    Full Text Available In research laboratories of both organic synthesis and extraction of natural products, every day a lot of products that can potentially introduce some biological activity are obtained. Therefore it is necessary to have in vitro assays, which provide reliable information for further evaluation in in vivo systems. From this point of view, in recent years has intensified the use of high-throughput screening assays. Such trials should be optimized and validated for accurate and precise results, i.e. reliable. The present review addresses the steps needed to develop and validate bioanalytical methods, emphasizing UV-Visible spectrophotometry as detection system. Particularly focuses on the selection of the method, the optimization to determine the best experimental conditions, validation, implementation of optimized and validated method to real samples, and finally maintenance and possible transfer it to a new laboratory.

  12. Development and validation of HPLC analytical method for quantitative determination of metronidazole in human plasma

    International Nuclear Information System (INIS)

    Safdar, K.A.; Shyum, S.B.; Usman, S.

    2016-01-01

    The objective of the present study was to develop a simple, rapid and sensitive reversed-phase high performance liquid chromatographic (RP-HPLC) analytical method with UV detection system for the quantitative determination of metronidazole in human plasma. The chromatographic separation was performed by using C18 RP column (250mm X 4.6mm, 5 meu m) as stationary phase and 0.01M potassium dihydrogen phosphate buffered at pH 3.0 and acetonitrile (83:17, v/v) as mobile phase at flow rate of 1.0 ml/min. The UV detection was carried out at 320nm. The method was validated as per the US FDA guideline for bioanalytical method validation and was found to be selective without interferences from mobile phase components, impurities and biological matrix. The method found to be linear over the concentration range of 0.2812 meu g/ml to 18.0 meu g/ml (r2 = 0.9987) with adequate level of accuracy and precision. The samples were found to be stable under various recommended laboratory and storage conditions. Therefore, the method can be used with adequate level of confidence and assurance for bioavailability, bioequivalence and other pharmacokinetic studies of metronidazole in human. (author)

  13. OVERVIEW OF VALIDATION, BASIC CONCEPTS AND ANALYTICAL METHOD PROCESS VALIDATION

    OpenAIRE

    Indu Gurram* , M.V.S.Kavitha, M.V.Nagabhushnam, Brahmaiah Bonthagara, D.Nagarjuna Reddy

    2017-01-01

    Quality is the primordial intention to any industry and its products manufactured. Multiple views on obtaining such quality are the current interest in the pharmaceutical industry. Validation is the art of designing and practicing the designed steps alongside with the documentation. Validation and quality assurance will go hand in hand, ensuring the through quality for the products. When analytical method is utilized to generate results about the characteristics of drug related samples it is ...

  14. Carbon Nanomaterials for Bioanalytical Sensing and Multicolor Cell Imaging

    OpenAIRE

    Lemberger, Michael-Maximilian

    2018-01-01

    The hydrothermal preparation of N-doped C-dots from starch and L-tryptophan which was developed and optimized represents a simple and sustainable synthetic method to obtain a highly interesting carbon nanomaterial for bioanalytical applications. These particles exhibit a size distribution between 0.5 and 4.5 nm with an average size of (1.6 ±0.8) nm. They furthermore show a high functionalization with oxygen containing-groups, remnants from the precursor molecules, which renders them highly wa...

  15. Spacecraft early design validation using formal methods

    NARCIS (Netherlands)

    Bozzano, Marco; Cimatti, Alessandro; Katoen, Joost P.; Katsaros, Panagiotis; Mokos, Konstantinos; Nguyen, Viet Yen; Noll, Thomas; Postma, Bart; Roveri, Marco

    2014-01-01

    The size and complexity of software in spacecraft is increasing exponentially, and this trend complicates its validation within the context of the overall spacecraft system. Current validation methods are labor-intensive as they rely on manual analysis, review and inspection. For future space

  16. Development and validation of a HILIC- MS/MS multi-targeted method for metabolomics applications.

    Science.gov (United States)

    Virgiliou, Christina; Sampsonidis, Ioannis; Gika, Helen G; Raikos, Nikolaos; Theodoridis, Georgios A

    2015-07-14

    The paper reports the development of a multi-analyte method and its application in metabolic profiling of biological fluids. The initial aim of the method was the quantification of metabolites existing in cell culture medium used in in-vitro fertilisation (IVF) and in other biological fluids related to embryo growth. Since most of these analytes are polar primary metabolites a hydrophilic interaction liquid chromatography (HILIC) system was selected. The analytical system comprised Ultra (High) performance liquid chromatography (UHPLC) with detection on a triple quadrupole mass spectrometer operating in both positive and negative modes. Mobile phase and gradient elution conditions were studied with the aim to achieve the highest coverage of metabolic space in a single injection namely the largest number of analytes that could be detected and quantified. The developed method provides absolute quantitation of ca. 100 metabolites belonging to key metabolite classes such as sugars, aminoacids, nucleotides, organic acids and amines. Following validation, the method was applied for the metabolic profiling of hundreds of samples of spent culture medium originating from human IVF procedures and several hundreds of biological samples such as amniotic fluid, human urine and blood serum from pregnant women. The bioanalytical end-point was to provide assistance in the process of embryo transfer and improving IVF success rates but also to provide insight in complications related to the subsequent embryo growth during pregnancy. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  17. Validated modified Lycopodium spore method development for ...

    African Journals Online (AJOL)

    Validated modified lycopodium spore method has been developed for simple and rapid quantification of herbal powdered drugs. Lycopodium spore method was performed on ingredients of Shatavaryadi churna, an ayurvedic formulation used as immunomodulator, galactagogue, aphrodisiac and rejuvenator. Estimation of ...

  18. ASTM Validates Air Pollution Test Methods

    Science.gov (United States)

    Chemical and Engineering News, 1973

    1973-01-01

    The American Society for Testing and Materials (ASTM) has validated six basic methods for measuring pollutants in ambient air as the first part of its Project Threshold. Aim of the project is to establish nationwide consistency in measuring pollutants; determining precision, accuracy and reproducibility of 35 standard measuring methods. (BL)

  19. Rapid validated liquid chromatographic method coupled with ...

    African Journals Online (AJOL)

    Abstract. Purpose: To develop and validate a fast, sensitive, and simple liquid chromatographic method coupled with tandem mass spectrometry for the ... European Medicines Agency (EMA) guidelines. Results: The proposed method ... that few articles were published for NTB quantification in rat biological fluids and tissues.

  20. 3D-printed bioanalytical devices

    Science.gov (United States)

    Bishop, Gregory W.; Satterwhite-Warden, Jennifer E.; Kadimisetty, Karteek; Rusling, James F.

    2016-07-01

    While 3D printing technologies first appeared in the 1980s, prohibitive costs, limited materials, and the relatively small number of commercially available printers confined applications mainly to prototyping for manufacturing purposes. As technologies, printer cost, materials, and accessibility continue to improve, 3D printing has found widespread implementation in research and development in many disciplines due to ease-of-use and relatively fast design-to-object workflow. Several 3D printing techniques have been used to prepare devices such as milli- and microfluidic flow cells for analyses of cells and biomolecules as well as interfaces that enable bioanalytical measurements using cellphones. This review focuses on preparation and applications of 3D-printed bioanalytical devices.

  1. Multianalytical Method Validation for Qualitative and Quantitative Analysis of Solvents of Abuse in Oral Fluid by HS-GC/MS

    Directory of Open Access Journals (Sweden)

    Bruna Claudia Coppe

    2016-01-01

    Full Text Available The use of oral fluid as a biological matrix to monitor the use of drugs of abuse is a global trend because it presents several advantages and good correlation to the blood level. Thus, the present work aimed to develop and validate an analytical method for quantification and detection of solvents used as inhalants of abuse in oral fluid (OF, using Quantisal™ as collector device by headspace and gas chromatography coupled with a mass detector (HS-GC/MS. Chromatographic separation was performed with a ZB-BAC1 column and the total time of analysis was 11.8 min. The method showed good linearity (correlation coefficient higher than 0.99 for all solvents. The limits of detection ranged from 0.05 to 5 mg/L, while the lower limits of quantification ranged from 2.5 to 12.5 mg/L. Accuracy, precision, matrix effect, and residual effect presented satisfactory results, meeting the criteria accepted for the validation of bioanalytical methods. The method showed good selectivity considering that, for solvents coeluting at the same retention time, resolution was performed by the mass detector. The method developed proved to be adequate when applied in OF samples from users of drugs and may be used to monitor the abuse of inhalants in routine forensic analyses.

  2. Model-Based Method for Sensor Validation

    Science.gov (United States)

    Vatan, Farrokh

    2012-01-01

    Fault detection, diagnosis, and prognosis are essential tasks in the operation of autonomous spacecraft, instruments, and in situ platforms. One of NASA s key mission requirements is robust state estimation. Sensing, using a wide range of sensors and sensor fusion approaches, plays a central role in robust state estimation, and there is a need to diagnose sensor failure as well as component failure. Sensor validation can be considered to be part of the larger effort of improving reliability and safety. The standard methods for solving the sensor validation problem are based on probabilistic analysis of the system, from which the method based on Bayesian networks is most popular. Therefore, these methods can only predict the most probable faulty sensors, which are subject to the initial probabilities defined for the failures. The method developed in this work is based on a model-based approach and provides the faulty sensors (if any), which can be logically inferred from the model of the system and the sensor readings (observations). The method is also more suitable for the systems when it is hard, or even impossible, to find the probability functions of the system. The method starts by a new mathematical description of the problem and develops a very efficient and systematic algorithm for its solution. The method builds on the concepts of analytical redundant relations (ARRs).

  3. Spacecraft early design validation using formal methods

    International Nuclear Information System (INIS)

    Bozzano, Marco; Cimatti, Alessandro; Katoen, Joost-Pieter; Katsaros, Panagiotis; Mokos, Konstantinos; Nguyen, Viet Yen; Noll, Thomas; Postma, Bart; Roveri, Marco

    2014-01-01

    The size and complexity of software in spacecraft is increasing exponentially, and this trend complicates its validation within the context of the overall spacecraft system. Current validation methods are labor-intensive as they rely on manual analysis, review and inspection. For future space missions, we developed – with challenging requirements from the European space industry – a novel modeling language and toolset for a (semi-)automated validation approach. Our modeling language is a dialect of AADL and enables engineers to express the system, the software, and their reliability aspects. The COMPASS toolset utilizes state-of-the-art model checking techniques, both qualitative and probabilistic, for the analysis of requirements related to functional correctness, safety, dependability and performance. Several pilot projects have been performed by industry, with two of them having focused on the system-level of a satellite platform in development. Our efforts resulted in a significant advancement of validating spacecraft designs from several perspectives, using a single integrated system model. The associated technology readiness level increased from level 1 (basic concepts and ideas) to early level 4 (laboratory-tested)

  4. Cellphone-based devices for bioanalytical sciences.

    Science.gov (United States)

    Vashist, Sandeep Kumar; Mudanyali, Onur; Schneider, E Marion; Zengerle, Roland; Ozcan, Aydogan

    2014-05-01

    During the last decade, there has been a rapidly growing trend toward the use of cellphone-based devices (CBDs) in bioanalytical sciences. For example, they have been used for digital microscopy, cytometry, read-out of immunoassays and lateral flow tests, electrochemical and surface plasmon resonance based bio-sensing, colorimetric detection and healthcare monitoring, among others. Cellphone can be considered as one of the most prospective devices for the development of next-generation point-of-care (POC) diagnostics platforms, enabling mobile healthcare delivery and personalized medicine. With more than 6.5 billion cellphone subscribers worldwide and approximately 1.6 billion new devices being sold each year, cellphone technology is also creating new business and research opportunities. Many cellphone-based devices, such as those targeted for diabetic management, weight management, monitoring of blood pressure and pulse rate, have already become commercially-available in recent years. In addition to such monitoring platforms, several other CBDs are also being introduced, targeting e.g., microscopic imaging and sensing applications for medical diagnostics using novel computational algorithms and components already embedded on cellphones. This report aims to review these recent developments in CBDs for bioanalytical sciences along with some of the challenges involved and the future opportunities.

  5. Bioanalytical outsourcing strategy at Janssen Research and Development.

    Science.gov (United States)

    Verhaeghe, Tom

    2014-05-01

    The times when all bioanalytical work was supported in-house are long behind us. In the modern bioanalytical laboratory, workload is divided between in-house support and outsourcing to contract research organizations. This paper outlines the outsourcing strategy of the Janssen-regulated bioanalytical group. Keeping the knowledge of the assay and the compound internally is a cornerstone of this strategy and is a driver for balancing the workload between the internal laboratory and contract laboratories. The number of contract laboratories that are being used is limited and criteria for selecting laboratories are discussed. Special attention is paid to the experience with outsourcing clinical studies to China.

  6. Sample preparation for large-scale bioanalytical studies based on liquid chromatographic techniques.

    Science.gov (United States)

    Medvedovici, Andrei; Bacalum, Elena; David, Victor

    2018-01-01

    Quality of the analytical data obtained for large-scale and long term bioanalytical studies based on liquid chromatography depends on a number of experimental factors including the choice of sample preparation method. This review discusses this tedious part of bioanalytical studies, applied to large-scale samples and using liquid chromatography coupled with different detector types as core analytical technique. The main sample preparation methods included in this paper are protein precipitation, liquid-liquid extraction, solid-phase extraction, derivatization and their versions. They are discussed by analytical performances, fields of applications, advantages and disadvantages. The cited literature covers mainly the analytical achievements during the last decade, although several previous papers became more valuable in time and they are included in this review. Copyright © 2017 John Wiley & Sons, Ltd.

  7. LC-APCI mass spectrometric method development and validation for the determination of atovaquone in human plasma.

    Science.gov (United States)

    Gurule, Sanjay; Goswami, Dipanjan; Khuroo, Arshad H; Monif, Tausif

    2010-05-01

    A newly developed LC-APCI mass spectrometric method is described for human plasma determination of atovaquone using lapachol internal standard. A single-step protein precipitation technique for plasma extraction of atovaquone achieving mean recovery of 94.17% (CV 8%) without compromising sensitivity (limit of quantitation 50.3 ng/mL) or linearity (50.3 ng/mL-23924.6 ng/mL) is delineated in this paper. Heated nebulizer in negative multiple reaction monitoring mode was employed with transitions m/z 365.2 --> m/z 337.1 and m/z 240.9 --> m/z 185.7 for atovaquone and lapachol respectively in this liquid chromatographic-tandem mass spectrometric method. Excellent chromatographic separation on a Synergi 4 micro Polar-RP 80A (150 x 2.0 mm) column, using 100 microL of plasma extraction volume along with 10 microL of injection load, completing analysis run-time within 2.5 min, highlights this simple yet unique bioanalytical method. The developed method can be successfully applied to pharmacokinetic studies on atovaquone suspension administered in healthy volunteers or HIV-infected patients. Moreover full method validation results not published before are presented and discussed in detail for the first time in this article. 2009 John Wiley & Sons, Ltd.

  8. Carbamazepine, lamotrigine, levetiracetam and valproic acid in dried blood spots with liquid chromatography tandem mass spectrometry; method development and validation.

    Science.gov (United States)

    Linder, Camilla; Hansson, Anna; Sadek, Sara; Gustafsson, Lars L; Pohanka, Anton

    2018-01-01

    Monitoring of antiepileptic drugs in children with epilepsy require multiple visits at a clinic for blood collection. Dried blood spot sampling is an alternative way of collection, performed at home by self-collection and can save time and costs for patients and family members. The aim was to develop and validate an LC-MS/MS dried blood spot method for carbamazepine, lamotrigine, levetiracetam and valproic acid with the requirements of using standard equipment and material in a routine laboratory setting. Whatman-903 filter paper was utilized, and discs were punched into a 96 well plate with an automated puncher and barcode reading. Extraction with methanol/water solution including internal standards on an orbital shaker was followed by a vacuum centrifuge step and reconstitution in mobile phase. Bioanalytical validation was performed according to guidelines from European Medicines Agency and additional dried blood spot specific validation. Calibration curves of the four included drugs had R 2 values ≥0.994. Therapeutic relevant concentrations were well within measuring ranges. Within and -between run precision had %CV:s of 2.9-10.5%. Accuracy (%bias) was between -16.5% (lower limit of quantification) to +7.4%. Blood spots in a volume range of 15-50μL with hematocrit in expected ranges for this patient group were within precision and accuracy limits. To test the method, concentrations from dried blood spot venous and capillary patient samples (n=50) were compared with plasma concentrations. Good correlations for all four drugs with R 2 of >0.92 was shown. In summary, a fast method for dried blood spots based on a 96 well format was developed for four commonly prescribed antiepileptic drugs. This validated method with traceability in sample preparation by bar code reading makes it suitable for the clinical laboratory. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Development and Validation of HPLC Method for Determination of Crocetin, a constituent of Saffron, in Human Serum Samples

    Directory of Open Access Journals (Sweden)

    Amir Hooshang Mohammadpour

    2013-01-01

    Full Text Available Objective(s:The present study reports the development and validation of a sensitive and rapid extraction method beside high performance liquid chromatographic method for the determination of crocetin in human serum. Materials and Methods:The HPLC method was carried out by using a C18 reversed-phase column and a mobile phase composed of methanol/water/acetic acid (85:14.5:0.5 v/v/v at the flow rate of 0.8 ml/min. The UV detector was set at 423 nm and 13-cis retinoic acid was used as the internal standard. Serum samples were pretreated with solid-phase extraction using Bond Elut C18 (200mg cartridges or with direct precipitation using acetonitrile. Results:The calibration curves were linear over the range of 0.05-1.25 µg/ml for direct precipitation method and 0.5-5 µg/ml for solid-phase extraction. The mean recoveries of crocetin over a concentration range of 0.05-5 µg/ml serum for direct precipitation method and 0.5-5 µg/ml for solid-phase extraction were above 70 % and 60 %, respectively. The intraday coefficients of variation were 0.37- 2.6% for direct precipitation method and 0.64 - 5.43% for solid-phase extraction. The inter day coefficients of variation were 1.69 – 6.03% for direct precipitation method and 5.13-12.74% for solid-phase extraction, respectively. The lower limit of quantification for crocetin was 0.05 µg/ml for direct precipitation method and 0.5 µg/ml for solid-phase extraction. Conclusion: The validated direct precipitation method for HPLC satisfied all of the criteria that were necessary for a bioanalytical method and could reliably quantitate crocetin in human serum for future clinical pharmacokinetic study

  10. Comparison of two-concentration with multi-concentration linear regressions: Retrospective data analysis of multiple regulated LC-MS bioanalytical projects.

    Science.gov (United States)

    Musuku, Adrien; Tan, Aimin; Awaiye, Kayode; Trabelsi, Fethi

    2013-09-01

    Linear calibration is usually performed using eight to ten calibration concentration levels in regulated LC-MS bioanalysis because a minimum of six are specified in regulatory guidelines. However, we have previously reported that two-concentration linear calibration is as reliable as or even better than using multiple concentrations. The purpose of this research is to compare two-concentration with multiple-concentration linear calibration through retrospective data analysis of multiple bioanalytical projects that were conducted in an independent regulated bioanalytical laboratory. A total of 12 bioanalytical projects were randomly selected: two validations and two studies for each of the three most commonly used types of sample extraction methods (protein precipitation, liquid-liquid extraction, solid-phase extraction). When the existing data were retrospectively linearly regressed using only the lowest and the highest concentration levels, no extra batch failure/QC rejection was observed and the differences in accuracy and precision between the original multi-concentration regression and the new two-concentration linear regression are negligible. Specifically, the differences in overall mean apparent bias (square root of mean individual bias squares) are within the ranges of -0.3% to 0.7% and 0.1-0.7% for the validations and studies, respectively. The differences in mean QC concentrations are within the ranges of -0.6% to 1.8% and -0.8% to 2.5% for the validations and studies, respectively. The differences in %CV are within the ranges of -0.7% to 0.9% and -0.3% to 0.6% for the validations and studies, respectively. The average differences in study sample concentrations are within the range of -0.8% to 2.3%. With two-concentration linear regression, an average of 13% of time and cost could have been saved for each batch together with 53% of saving in the lead-in for each project (the preparation of working standard solutions, spiking, and aliquoting). Furthermore

  11. The Method of Manufactured Universes for validating uncertainty quantification methods

    KAUST Repository

    Stripling, H.F.

    2011-09-01

    The Method of Manufactured Universes is presented as a validation framework for uncertainty quantification (UQ) methodologies and as a tool for exploring the effects of statistical and modeling assumptions embedded in these methods. The framework calls for a manufactured reality from which experimental data are created (possibly with experimental error), an imperfect model (with uncertain inputs) from which simulation results are created (possibly with numerical error), the application of a system for quantifying uncertainties in model predictions, and an assessment of how accurately those uncertainties are quantified. The application presented in this paper manufactures a particle-transport universe, models it using diffusion theory with uncertain material parameters, and applies both Gaussian process and Bayesian MARS algorithms to make quantitative predictions about new experiments within the manufactured reality. The results of this preliminary study indicate that, even in a simple problem, the improper application of a specific UQ method or unrealized effects of a modeling assumption may produce inaccurate predictions. We conclude that the validation framework presented in this paper is a powerful and flexible tool for the investigation and understanding of UQ methodologies. © 2011 Elsevier Ltd. All rights reserved.

  12. A validated method for the quantification of curcumin in plasma and brain tissue by fast narrow-bore high-performance liquid chromatography with fluorescence detection.

    Science.gov (United States)

    Schiborr, Christina; Eckert, Gunter P; Rimbach, Gerald; Frank, Jan

    2010-07-01

    Curcumin, a lipophilic polyphenol derived from the rhizome of the plant turmeric (Curcuma longa), might be useful in the prevention and treatment of a number of degenerative brain disorders, including glioma multiforma and Alzheimer's disease. Thus, there is growing interest in measuring curcumin concentrations in the brain and other target tissues in relevant animal models. We therefore developed and validated (according to the Food and Drug Administration guidelines for bioanalytical method validation), a simple, fast and reliable method for the quantification of curcumin in biological matrices by fast high-performance liquid chromatography with fluorescence detection. This method involves a simple extraction with 95% ethyl acetate and 5% methanol, rapid separation (curcumin. The developed method was used for the quantification of curcumin in the brains of mice force-fed (50 mg/kg bw) or i.p. injected (100 mg/kg bw) with curcumin. Brain curcumin concentrations of the mice were below the limit of detection at 30, 60 and 120 min after oral gavage and reached 4-5 microg/g brain 20-40 min after i.p. injection. In conclusion, the developed and validated method should be useful for the accurate and precise quantification of curcumin in target organs from relevant animal models of human diseases.

  13. Development and validation of a high throughput LC–MS/MS method for simultaneous quantitation of pioglitazone and telmisartan in rat plasma and its application to a pharmacokinetic study

    Directory of Open Access Journals (Sweden)

    Pinaki Sengupta

    2017-12-01

    Full Text Available Management of cardiovascular risk factors in diabetes demands special attention due to their co-existence. Pioglitazone (PIO and telmisartan (TLM combination can be beneficial in effective control of cardiovascular complication in diabetes. In this research, we developed and validated a high throughput LC–MS/MS method for simultaneous quantitation of PIO and TLM in rat plasma. This developed method is more sensitive and can quantitate the analytes in relatively shorter period of time compared to the previously reported methods for their individual quantification. Moreover, till date, there is no bioanalytical method available to simultaneously quantitate PIO and TLM in a single run. The method was validated according to the USFDA guidelines for bioanalytical method validation. A linear response of the analytes was observed over the range of 0.005–10 µg/mL with satisfactory precision and accuracy. Accuracy at four quality control levels was within 94.27%–106.10%. The intra- and inter-day precision ranged from 2.32%–10.14 and 5.02%–8.12%, respectively. The method was reproducible and sensitive enough to quantitate PIO and TLM in rat plasma samples of a preclinical pharmacokinetic study. Due to the potential of PIO-TLM combination to be therapeutically explored, this method is expected to have significant usefulness in future. Keywords: LC–MS/MS, Rat plasma, Pharmacokinetic applicability, Telmisartan, Pioglitazone, Pharmacokinetic application

  14. Development and Validation of a Dissolution Test Method for ...

    African Journals Online (AJOL)

    Purpose: To develop and validate a dissolution test method for dissolution release of artemether and lumefantrine from tablets. Methods: A single dissolution method for evaluating the in vitro release of artemether and lumefantrine from tablets was developed and validated. The method comprised of a dissolution medium of ...

  15. Random Qualitative Validation: A Mixed-Methods Approach to Survey Validation

    Science.gov (United States)

    Van Duzer, Eric

    2012-01-01

    The purpose of this paper is to introduce the process and value of Random Qualitative Validation (RQV) in the development and interpretation of survey data. RQV is a method of gathering clarifying qualitative data that improves the validity of the quantitative analysis. This paper is concerned with validity in relation to the participants'…

  16. Sensitive and validated spectrophotometric methods for the ...

    African Journals Online (AJOL)

    The methods involve the addition of a known excess of NBS to PNT in HCl medium followed by estimation of the unreacted oxidant by two reaction schemes involving the use of iron(II) and thiocyanate (method A) or tiron (method B). In both methods, the absorbance is found to decrease linearly with PNT concentration.

  17. A new high-performance liquid chromatography-tandem mass spectrometry method for the determination of paclitaxel and 6α-hydroxy-paclitaxel in human plasma: Development, validation and application in a clinical pharmacokinetic study.

    Science.gov (United States)

    Posocco, Bianca; Buzzo, Mauro; Follegot, Andrea; Giodini, Luciana; Sorio, Roberto; Marangon, Elena; Toffoli, Giuseppe

    2018-01-01

    Paclitaxel belongs to the taxanes family and it is used, alone or in multidrug regimens, for the therapy of several solid tumours, such as breast-, lung-, head and neck-, and ovarian cancer. Standard dosing of chemotherapy does not take into account the many inter-patient differences that make drug exposure highly variable, thus leading to the insurgence of severe toxicity. This is particularly true for paclitaxel considering that a relationship between haematological toxicity and plasma exposure was found. Therefore, in order to treat patients with the correct dose of paclitaxel, improving the overall benefit-risk ratio, Therapeutic Drug Monitoring is necessary. In order to quantify paclitaxel and its main metabolite, 6α-hydroxy-paclitaxel, in patients' plasma, we developed a new, sensitive and specific HPLC-MS/MS method applicable to all paclitaxel dosages used in clinical routine. The developed method used a small volume of plasma sample and is based on quick protein precipitation. The chromatographic separation of the analytes was achieved with a SunFire™ C18 column (3.5 μM, 92 Å, 2,1 x 150 mm); the mobile phases were 0.1% formic acid/bidistilled water and 0.1% formic acid/acetonitrile. The electrospray ionization source worked in positive ion mode and the mass spectrometer operated in selected reaction monitoring mode. Our bioanalytical method was successfully validated according to the FDA-EMA guidelines on bioanalytical method validation. The calibration curves resulted linear (R2 ≥0.9948) over the concentration ranges (1-10000 ng/mL for paclitaxel and 1-1000 ng/mL for 6α-hydroxy-paclitaxel) and were characterized by a good accuracy and precision. The intra- and inter-day precision and accuracy were determined on three quality control concentrations for paclitaxel and 6α-hydroxy-paclitaxel and resulted respectively <9.9% and within 91.1-114.8%. In addition, to further verify the assay reproducibility, we tested this method by re-analysing the

  18. Experimental Validation of a Risk Assessment Method

    NARCIS (Netherlands)

    Vriezekolk, E.; Etalle, Sandro; Wieringa, Roelf J.

    [Context and motivation] It is desirable that require- ment engineering methods are reliable, that is, that methods can be repeated with the same results. Risk assessments methods, however, often have low reliability when they identify risk mitigations for a sys- tem based on expert judgement.

  19. Validation Method of a Telecommunications Blackout Attack

    National Research Council Canada - National Science Library

    Amado, Joao; Nunes, Paulo

    2005-01-01

    This paper presents an evaluation method of telecommunications infrastructure vulnerabilities, allowing the identification of components that can be attacked in order to achieve a communications blackout...

  20. Validated High Performance Liquid Chromatography Method for ...

    African Journals Online (AJOL)

    Purpose: To develop a simple, rapid and sensitive high performance liquid chromatography (HPLC) method for the determination of cefadroxil monohydrate in human plasma. Methods: Schimadzu HPLC with LC solution software was used with Waters Spherisorb, C18 (5 μm, 150mm × 4.5mm) column. The mobile phase ...

  1. A validated UHPLC-QTOF-MS method for quantification of metformin and teneligliptin in rat plasma: Application to pharmacokinetic interaction study.

    Science.gov (United States)

    Paul, David; Allakonda, Lingesh; Satheeshkumar, Nanjappan

    2017-09-05

    In this study a sensitive UHPLC-QTOF-MS method was developed and validated for the quantitation of the metformin (MET) and teneligliptin (TEN) in rat plasma using dapagliflozin as an internal standard (IS). Chromatographic separation were carried out on a Acquity UPLC HSS Cyano column (100mm x 2.1mm, 1.8μm) using gradient mobile phase system consisting of 0.1% formic acid and acetonitrile at a flow rate of 0.4mL/min, within a run time of 6min. Protein precipitation method was used as sample preparation approach. Detection of target ions [M+H] + at m/z 130.1085 for MET, m/z 427.2277 for TEN and m/z 409.1623 for IS was performed at positive ion electrospray ionization mode. Linearity was assessed in the range of 0.98-1000ng/mL for both MET and TEN. The developed assay was validated as per US-FDA and EMA bioanalytical guidelines and successfully applied to pharmacokinetic interaction study in SD rats. A 1.1 fold increment in the AUC levels of MET and TEN was observed when co-administered together in rats. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Validation of qualitative microbiological test methods

    NARCIS (Netherlands)

    IJzerman-Boon, Pieta C.; van den Heuvel, Edwin R.

    2015-01-01

    This paper considers a statistical model for the detection mechanism of qualitative microbiological test methods with a parameter for the detection proportion (the probability to detect a single organism) and a parameter for the false positive rate. It is demonstrated that the detection proportion

  3. Validated High Performance Liquid Chromatography Method for ...

    African Journals Online (AJOL)

    capsules and dry powder for oral suspension, manufactured by local and multinational companies. It is an official monograph in United. States Pharmacopeia (USP) [3]. Cefadroxil monohydrate has been quantitatively determined in biological fluids, including plasma, serum, and urine [4-16]. Many analytical methods were.

  4. Validation of Land Cover Products Using Reliability Evaluation Methods

    OpenAIRE

    Shi, Wenzhong; Zhang, Xiaokang; Hao, Ming; Shao, Pan; Cai, Liping; Lyu, Xuzhe

    2015-01-01

    Validation of land cover products is a fundamental task prior to data applications. Current validation schemes and methods are, however, suited only for assessing classification accuracy and disregard the reliability of land cover products. The reliability evaluation of land cover products should be undertaken to provide reliable land cover information. In addition, the lack of high-quality reference data often constrains validation and affects the reliability results of land cover products. ...

  5. Validation of analytical methods based on accuracy profiles.

    Science.gov (United States)

    Feinberg, Max

    2007-07-27

    Validation is a very living field in analytical chemistry as illustrated by the numerous publications addressing this topic. But, there is some ambiguity in this concept and the abundant vocabulary often does not help the analytical chemist. This paper presents a new method based on the fitness-for-purpose approach of the validation. It consists in building a graphical decision-making tool, called the accuracy profile. Using measurements collected under reproducibility or intermediate precision condition, it allows computing an interval where a known proportion of future measurements will be located. When comparing this interval to an acceptability interval defined by the result end-user it is possible to simply decide whether a method is valid or not. The fundamentals of this method are presented starting from an accepted definition of validation. An example of application illustrates how validation can be experimentally organized and conclusion made.

  6. A preliminary investigation of PSA validation methods

    International Nuclear Information System (INIS)

    Unwin, S.D.

    1995-09-01

    This document has been prepared to support the initial phase of the Atomic Energy Control Board's program to review and evaluate Probabilistic Safety Assessment (PSA) studies conducted by nuclear generating station designers and licensees. The document provides (1) a review of current and prospective applications of PSA technology in the Canadian nuclear power industry; (2) an assessment of existing practices and techniques for the review or risk and hazard identification studies in the international nuclear power sector and other technological sectors; and (3) proposed analytical framework in which to develop systematic techniques for the scrutiny and evaluation of a PSA model. These frameworks are based on consideration of the mathematical structure of a PSA model and are intended to facilitate the development of methods to evaluate a model relative to intended end-uses. (author). 34 refs., 10 tabs., 3 figs

  7. Investigation of the effect of plasma albumin levels on regorafenib-induced hepatotoxicity using a validated liquid chromatography-tandem mass spectrometry method.

    Science.gov (United States)

    Pang, Yi Yun; Tan, Yeong Lan; Ho, Han Kiat

    2017-09-01

    Regorafenib is an oral multikinase inhibitor indicated for metastatic colorectal cancer and gastrointestinal stromal tumour. Due to its extensive plasma protein binding and low calculated hepatic extraction ratio, the hepatotoxicity observed with usage of the drug may be related to its plasma exposure. To investigate the highly dynamic free:bound drug concentration for regorafenib in the plasma, a bioanalytical liquid chromatography-tandem mass spectrometric assay was developed and validated in human plasma. The concentration range of the assay was 2-1000ng/mL. Sample preparation was via protein precipitation using acetonitrile with sorafenib as the internal standard. The supernatant was injected into an ultra-performance liquid chromatographic system coupled to a triple quadrupole mass spectrometer. The analytes were separated on an AQUITY UPLC BEH C 18 column (120Å, 1.7μm, 2.1mm×50mm) and eluted with a gradient elution system. The ions were detected in multiple reaction monitoring mode. The linearity, lower limit of quantification, intra-day and inter-day precision and accuracy conformed to FDA guidelines. The validated method was successfully applied to determine the effect of albumin levels in plasma on the extent of protein binding of regorafenib. The results indicated that physiologically-relevant levels of albumin were found to have no significant effect on the extent of protein binding of regorafenib, hence imposing minimal effect on drug disposition. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. VALIDATION OF CYCLAMATE ANALYSIS METHOD WITH SPECTROPHOTOMETRY AND TURBIDIMETRY

    OpenAIRE

    Regina Tutik Padmaningrum; Siti Marwati

    2016-01-01

    This research aims to validate methods of analysis by spectrophotometry and turbidimetry cyclamate in the sample drink mango-flavored jelly drink  by spectrophotometry with hypochlorite reagent, ultraviolet spectrophotometry (without reagent) and turbidimetry. The object of research was the validity parameters spectrophotometric method were linearity, linear range, the limit of detection, limit of quantitation, precision, and accuracy. The calibration curve of standard solution of sodium cycl...

  9. Reliability and validity of optoelectronic method for biophotonical measurements

    Science.gov (United States)

    Karpienko, Katarzyna; Wróbel, Maciej S.; UrniaŻ, Rafał

    2013-11-01

    Reliability and validity of measurements is of utmost importance when assessing measuring capability of instruments developed for research. In order to perform an experiment which is legitimate, used instruments must be both reliable and valid. Reliability estimates the degree of precision of measurement, the extent to which a measurement is internally consistent. Validity is the usefulness of an instrument to perform accurate measurements of quantities it was designed to measure. Statistical analysis for reliability and validity control of low-coherence interferometry method for refractive index measurements of biological fluids is presented. The low-coherence interferometer is sensitive to optical path difference between interfering beams. This difference depends on the refractive index of measured material. To assess the validity and reliability of proposed method for blood measurements, the statistical analysis of the method was performed on several substances with known refractive indices. Analysis of low-coherence interferograms considered the mean distances between fringes. Performed statistical analysis for validity and reliability consisted of Grubb's test for outliers, Shapiro-Wilk test for normal distribution, T-Student test, standard deviation, coefficient of determination and r-Pearson correlation. Overall the tests proved high statistical significance of measurement method with confidence level measurement method.

  10. International Harmonization and Cooperation in the Validation of Alternative Methods.

    Science.gov (United States)

    Barroso, João; Ahn, Il Young; Caldeira, Cristiane; Carmichael, Paul L; Casey, Warren; Coecke, Sandra; Curren, Rodger; Desprez, Bertrand; Eskes, Chantra; Griesinger, Claudius; Guo, Jiabin; Hill, Erin; Roi, Annett Janusch; Kojima, Hajime; Li, Jin; Lim, Chae Hyung; Moura, Wlamir; Nishikawa, Akiyoshi; Park, HyeKyung; Peng, Shuangqing; Presgrave, Octavio; Singer, Tim; Sohn, Soo Jung; Westmoreland, Carl; Whelan, Maurice; Yang, Xingfen; Yang, Ying; Zuang, Valérie

    The development and validation of scientific alternatives to animal testing is important not only from an ethical perspective (implementation of 3Rs), but also to improve safety assessment decision making with the use of mechanistic information of higher relevance to humans. To be effective in these efforts, it is however imperative that validation centres, industry, regulatory bodies, academia and other interested parties ensure a strong international cooperation, cross-sector collaboration and intense communication in the design, execution, and peer review of validation studies. Such an approach is critical to achieve harmonized and more transparent approaches to method validation, peer-review and recommendation, which will ultimately expedite the international acceptance of valid alternative methods or strategies by regulatory authorities and their implementation and use by stakeholders. It also allows achieving greater efficiency and effectiveness by avoiding duplication of effort and leveraging limited resources. In view of achieving these goals, the International Cooperation on Alternative Test Methods (ICATM) was established in 2009 by validation centres from Europe, USA, Canada and Japan. ICATM was later joined by Korea in 2011 and currently also counts with Brazil and China as observers. This chapter describes the existing differences across world regions and major efforts carried out for achieving consistent international cooperation and harmonization in the validation and adoption of alternative approaches to animal testing.

  11. Practical procedure for method validation in INAA- A tutorial

    International Nuclear Information System (INIS)

    Petroni, Robson; Moreira, Edson G.

    2015-01-01

    This paper describes the procedure employed by the Neutron Activation Laboratory at the Nuclear and Energy Research Institute (LAN, IPEN - CNEN/SP) for validation of Instrumental Neutron Activation Analysis (INAA) methods. According to recommendations of ISO/IEC 17025 the method performance characteristics (limit of detection, limit of quantification, trueness, repeatability, intermediate precision, reproducibility, selectivity, linearity and uncertainties budget) were outline in an easy, fast and convenient way. The paper presents step by step how to calculate the required method performance characteristics in a process of method validation, what are the procedures, adopted strategies and acceptance criteria for the results, that is, how to make a method validation in INAA. In order to exemplify the methodology applied, obtained results for the method validation of mass fraction determination of Co, Cr, Fe, Rb, Se and Zn in biological matrix samples, using an internal reference material of mussel tissue were presented. It was concluded that the methodology applied for validation of INAA methods is suitable, meeting all the requirements of ISO/IEC 17025, and thereby, generating satisfactory results for the studies carried at LAN, IPEN - CNEN/SP. (author)

  12. Practical procedure for method validation in INAA- A tutorial

    Energy Technology Data Exchange (ETDEWEB)

    Petroni, Robson; Moreira, Edson G., E-mail: robsonpetroni@usp.br [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)

    2015-07-01

    This paper describes the procedure employed by the Neutron Activation Laboratory at the Nuclear and Energy Research Institute (LAN, IPEN - CNEN/SP) for validation of Instrumental Neutron Activation Analysis (INAA) methods. According to recommendations of ISO/IEC 17025 the method performance characteristics (limit of detection, limit of quantification, trueness, repeatability, intermediate precision, reproducibility, selectivity, linearity and uncertainties budget) were outline in an easy, fast and convenient way. The paper presents step by step how to calculate the required method performance characteristics in a process of method validation, what are the procedures, adopted strategies and acceptance criteria for the results, that is, how to make a method validation in INAA. In order to exemplify the methodology applied, obtained results for the method validation of mass fraction determination of Co, Cr, Fe, Rb, Se and Zn in biological matrix samples, using an internal reference material of mussel tissue were presented. It was concluded that the methodology applied for validation of INAA methods is suitable, meeting all the requirements of ISO/IEC 17025, and thereby, generating satisfactory results for the studies carried at LAN, IPEN - CNEN/SP. (author)

  13. Magnetic Particle-Based Hybrid Platforms for Bioanalytical Sensors

    Directory of Open Access Journals (Sweden)

    Silvana Andreescu

    2009-04-01

    Full Text Available Biomagnetic nano and microparticles platforms have attracted considerable interest in the field of biological sensors due to their interesting physico-chemical properties, high specific surface area, good mechanical stability and opportunities for generating magneto-switchable devices. This review discusses recent advances in the development and characterization of active biomagnetic nanoassemblies, their interaction with biological molecules and their use in bioanalytical sensors.

  14. Fundamentals and applications of SERS-based bioanalytical sensing

    Science.gov (United States)

    Kahraman, Mehmet; Mullen, Emma R.; Korkmaz, Aysun; Wachsmann-Hogiu, Sebastian

    2017-03-01

    Plasmonics is an emerging field that examines the interaction between light and metallic nanostructures at the metal-dielectric interface. Surface-enhanced Raman scattering (SERS) is a powerful analytical technique that uses plasmonics to obtain detailed chemical information of molecules or molecular assemblies adsorbed or attached to nanostructured metallic surfaces. For bioanalytical applications, these surfaces are engineered to optimize for high enhancement factors and molecular specificity. In this review we focus on the fabrication of SERS substrates and their use for bioanalytical applications. We review the fundamental mechanisms of SERS and parameters governing SERS enhancement. We also discuss developments in the field of novel SERS substrates. This includes the use of different materials, sizes, shapes, and architectures to achieve high sensitivity and specificity as well as tunability or flexibility. Different fundamental approaches are discussed, such as label-free and functional assays. In addition, we highlight recent relevant advances for bioanalytical SERS applied to small molecules, proteins, DNA, and biologically relevant nanoparticles. Subsequently, we discuss the importance of data analysis and signal detection schemes to achieve smaller instruments with low cost for SERS-based point-of-care technology developments. Finally, we review the main advantages and challenges of SERS-based biosensing and provide a brief outlook.

  15. Fundamentals and applications of SERS-based bioanalytical sensing

    Directory of Open Access Journals (Sweden)

    Kahraman Mehmet

    2017-03-01

    Full Text Available Plasmonics is an emerging field that examines the interaction between light and metallic nanostructures at the metal-dielectric interface. Surface-enhanced Raman scattering (SERS is a powerful analytical technique that uses plasmonics to obtain detailed chemical information of molecules or molecular assemblies adsorbed or attached to nanostructured metallic surfaces. For bioanalytical applications, these surfaces are engineered to optimize for high enhancement factors and molecular specificity. In this review we focus on the fabrication of SERS substrates and their use for bioanalytical applications. We review the fundamental mechanisms of SERS and parameters governing SERS enhancement. We also discuss developments in the field of novel SERS substrates. This includes the use of different materials, sizes, shapes, and architectures to achieve high sensitivity and specificity as well as tunability or flexibility. Different fundamental approaches are discussed, such as label-free and functional assays. In addition, we highlight recent relevant advances for bioanalytical SERS applied to small molecules, proteins, DNA, and biologically relevant nanoparticles. Subsequently, we discuss the importance of data analysis and signal detection schemes to achieve smaller instruments with low cost for SERS-based point-of-care technology developments. Finally, we review the main advantages and challenges of SERS-based biosensing and provide a brief outlook.

  16. Development and Validation of Improved Method for Fingerprint ...

    African Journals Online (AJOL)

    Purpose: To develop and validate an improved method by capillary zone electrophoresis with photodiode array detection for the fingerprint analysis of Ligusticum chuanxiong Hort. (Rhizoma Chuanxiong). Methods: The optimum high performance capillary electrophoresis (HPCE) conditions were 30 mM borax containing 5 ...

  17. Validated method for the detection and quantitation of synthetic ...

    African Journals Online (AJOL)

    Validated method for the detection and quantitation of synthetic cannabinoids in whole blood and urine, and its application to postmortem cases in Johannesburg, South ... A LC-HRMS (liquid chromatography coupled with high resolution mass spectrometry) method for the detection and quantitation of several synthetic ...

  18. Predictive validity of the Hand Arm Risk assessment Method (HARM)

    NARCIS (Netherlands)

    Douwes, M.; Boocock, M.; Coenen, P.; Heuvel, S. van den; Bosch, T.

    2014-01-01

    The Hand Arm Risk assessment Method (HARM) is a simplified risk assessment method for determining musculoskeletal symptoms to the arm, neck and/or shoulder posed by hand-arm tasks of the upper body. The purpose of this study was to evaluate the predictive validity of HARM using data collected from a

  19. Development and Validation of Analytical Method for Losartan ...

    African Journals Online (AJOL)

    Development and Validation of Analytical Method for Losartan-Copper Complex Using UV-Vis Spectrophotometry. ... Tropical Journal of Pharmaceutical Research ... Purpose: To develop a new spectrophotometric method for the analysis of losartan potassium in pharmaceutical formulations by making its complex with ...

  20. Validation of NAA Method for Urban Particulate Matter

    International Nuclear Information System (INIS)

    Woro Yatu Niken Syahfitri; Muhayatun; Diah Dwiana Lestiani; Natalia Adventini

    2009-01-01

    Nuclear analytical techniques have been applied in many countries for determination of environmental pollutant. Method of NAA (neutron activation analysis) representing one of nuclear analytical technique of that has low detection limits, high specificity, high precision, and accuracy for large majority of naturally occurring elements, and ability of non-destructive and simultaneous determination of multi-elemental, and can handle small sample size (< 1 mg). To ensure quality and reliability of the method, validation are needed to be done. A standard reference material, SRM NIST 1648 Urban Particulate Matter, has been used to validate NAA method. Accuracy and precision test were used as validation parameters. Particulate matter were validated for 18 elements: Ti, I, V, Br, Mn, Na, K, Cl, Cu, Al, As, Fe, Co, Zn, Ag, La, Cr, and Sm,. The result showed that the percent relative standard deviation of the measured elemental concentrations are found to be within ranged from 2 to 14,8% for most of the elements analyzed whereas Hor rat value in range 0,3-1,3. Accuracy test results showed that relative bias ranged from -11,1 to 3,6%. Based on validation results, it can be stated that NAA method is reliable for characterization particulate matter and other similar matrix samples to support air quality monitoring. (author)

  1. VALIDATION OF CYCLAMATE ANALYSIS METHOD WITH SPECTROPHOTOMETRY AND TURBIDIMETRY

    Directory of Open Access Journals (Sweden)

    Regina Tutik Padmaningrum

    2016-04-01

    Full Text Available This research aims to validate methods of analysis by spectrophotometry and turbidimetry cyclamate in the sample drink mango-flavored jelly drink  by spectrophotometry with hypochlorite reagent, ultraviolet spectrophotometry (without reagent and turbidimetry. The object of research was the validity parameters spectrophotometric method were linearity, linear range, the limit of detection, limit of quantitation, precision, and accuracy. The calibration curve of standard solution of sodium cyclamate in the spectrophotometric method with hypochlorite reagent, UV spectrophotometry (without reagent, and turbidimetry are linear. Linear range each method respectively at a concentration were (211.36-747.08; (16.000-146.434; and (1.8521-6.1717 ppm. The detection limit of each method successively were 53.6028; 0.5833; and 0.2723 ppm. Limit of quantitation each method successively were 66.9948; 1.9443; and 0.8068 ppm. Spectrophotometric analysis method cyclamate with hypochlorite reagent had good precision and accuracy. Ultra violet  spectrophotometric analysis method of cyclamate have a good precision but the accuracy was not good. Turbidimetric methods  analysis of cyclamate had  precision and accuracy were not good. Keywords:   method validation, spectrophotometry, turbidimetry, cyclamate

  2. The validation and regulatory acceptance of alternative methods in Japan.

    Science.gov (United States)

    Ohno, Yasuo

    2004-06-01

    Except for the genotoxicity test, there are two regulatory guidelines in Japan for in vitro toxicity studies. One of them is a cytotoxicity test for the safety evaluation of extracts from plastic devices for medical use. The other is an in vitro endotoxin test (the Limulus test). These are included in the Japanese Pharmacopoeia. Japan also accepts data obtained from these tests conducted according to OECD guidelines. On the other hand, the Ministry of Health and Welfare (MHW) indicated in 1996 that they would accept alternatives to the Draize eye irritation test for safety evaluation of cosmetics if the method were appropriate. Therefore, the MHW/Japan Cosmetic Industry Association validation group conducted validation studies on alternative methods and indicated that the results of several cytotoxicity tests correlated very well with those of Draize scores obtained from rabbit tests. Based on the results, draft guidelines to evaluate the eye irritation potential of cosmetic ingredients were prepared and submitted to the MHW 1999, in which in vitro methods were incorporated. Validation requires a lot of resources and time. Therefore, we recently constructed an evaluation scheme for alternative methods with the support of the Ministry. This was based on the research, on published manuscripts, and on validation reports. We intended to clarify the performance of the method with its limitations. Without having this information, both regulators and industry persons would make big mistakes in evaluating the results of alternative methods. As a first trial of the project, research on the in vitro phototoxicity test was conducted.

  3. Alternative methods for ocular toxicology testing: validation, applications and troubleshooting.

    Science.gov (United States)

    Dholakiya, Sanjay L; Barile, Frank A

    2013-06-01

    Humanitarian concern, scientific progress and legislative action have lead to the development, validation and regulatory acceptance of alternative in vitro ocular models. However, to date not a single in vitro alternative ocular toxicity test has been validated as a full replacement for the in vivo Draize rabbit eye test for all classes of chemicals across whole irritancy ranges. Since the 1990s, ocular alternative methods have been validated but few have been accepted for regulatory purposes. These assays include: organotypic models, such as the bovine corneal opacity and permeability (BCOP) assay, the isolated chicken eye (ICE) test method and cell function-based in vitro assays, such as the cytosensor microphysiometer (CM) and the fluorescein leakage (FL) test methods. Some refinements to in vivo testing methods have been accepted by regulatory agencies, including humane endpoints to avoid or minimize pain and distress. The authors provide a review of the background, protocol overview, applications and their validation status of the tier-testing approach. Furthermore, the authors provide expert analysis and provide their perspective on this approach and potential future developments. In the search for a battery of methods that replaces the in vivo Draize test, it is necessary to prioritize techniques, define related mechanisms and justify statistical approaches. Overall, only when the reliability and relevance of a method is unequivocally supported will any technique be ready for regulatory acceptance.

  4. Determination of benzophenones in lipophilic extract of Brazilian red propolis, nanotechnology-based product and porcine skin and mucosa: Analytical and bioanalytical assays.

    Science.gov (United States)

    Fasolo, Daniel; Bergold, Ana Maria; von Poser, Gilsane; Teixeira, Helder Ferreira

    2016-05-30

    Lipophilic compounds of Brazilian Red Propolis (BRP) have received increasing attention due to some interesting findings regarding their biological activities. This study was first aimed at evaluating the chemical composition of BRP n-hexane extract (HEXred) by UPLC-MS-PDA. Chemical investigation mainly resulted in the identification of polyprenylated benzophenones (PPBs) in this extract, named oblongifolin A, guttiferone E, and/or xanthochymol. After that, an isocratic HPLC-UV method was validated for the determination of total content of PPBs (at 260 nm) expressed as garcinol, a commercially available guttiferone E diastereoisomer. The method showed to be specific, precise, accurate, and linear (0.1-10 μg/mL) for the determination of PPBs in HEXred, BRP-loaded nanoemulsions, as well as, in porcine skin and mucosa samples after permeation/retention studies. The matrix effect was determined for all complex matrices, demonstrating low effect during the analysis. The stability-indicating method was verified by submitting HEXred to acidic, alkaline, oxidative, and thermal stress conditions. No interference of degradation products was detected during analysis. Therefore, the proposed analytical and bioanalytical methods proved to be simple and reliable for the determination of PPBs in the presence of different matrices. Copyright © 2016 Elsevier B.V. All rights reserved.

  5. Multifunctional Nanomaterials Utilizing Hybridization Chain Reaction for Molecular Diagnostics and Bioanalytical Applications

    Science.gov (United States)

    Rana, Md. Muhit

    DNA nanotechnology has shown great promise in molecular diagnostic, bioanalytical and biomedical applications. The great challenge of detecting target analytes, biomarkers and small molecules, in molecular diagnostics is low yield sensitivity. To address this challenge, different nanomaterials have been used for a long time and to date there is no such cost-effective bioanalytical technique which can detect these target biomarkers (DNA, RNA, circulating DNA/miRNA) or environmental heavy metal ions (Hg2+ and Ag+) in a cost-effective and efficient manner. Herein, we initially discuss two possible bioanalytical detection methods- a) colorimetric and b) fluorometric assays which are very popular nowadays due to their distinctive spectroscopic properties. Finally, we report the promising colorimetric assay using a novel DNA based amplification strategy know as hybridization chain reaction (HCR) for potential application in the visual detection of low copies of biomarkers (miRNAs as little as 20 femtomole in an RNA pool and cell extracts in seven different combinations and Ebola virus DNA as low as 400 attomoles in liquid biopsy mimics in sixteen different combinations), environmental and biological heavy metal ions (mercury and silver concentrations as low as 10 pM in water, soil and urine samples) and also successfully applied to a molecular logic gate operation to distinguish OR and AND logic gates. No results showed any false-positive or false-negative information. On the other hand, we also discuss the future possibilities of HCR amplification technology, which is very promising for fluorometric bioanalysis. The HCR based nanoprobe technology has numerous remarkable advantages over other methods. It is re-programmable, simple, inexpensive, easy to assemble and operate and can be performed with visual and spectroscopic read-outs upon recognition of the target analytes. This rapid, specific and sensitive approach for biomarkers and heavy metal ion detection generates

  6. An experimental method for validating compressor valve vibration theory

    NARCIS (Netherlands)

    Habing, R.A.; Peters, M.C.A.M.

    2006-01-01

    This paper presents an experimental method for validating traditional compressor valve theory for unsteady flow conditions. Traditional valve theory considers the flow force acting on the plate and the flow rate as quasi-steady variables. These variables are related via semi-empirical coefficients

  7. Validated RP-HPLC Method for Quantification of Phenolic ...

    African Journals Online (AJOL)

    Purpose: To evaluate the total phenolic content and antioxidant potential of the methanol extracts of aerial parts and roots of Thymus sipyleus Boiss and also to determine some phenolic compounds using a newly developed and validated reversed phase high performance liquid chromatography (RP-HPLC) method.

  8. Development and Validation of a Liquid Chromatographic Method ...

    African Journals Online (AJOL)

    A liquid chromatographic method for the simultaneous determination of six human immunodeficiency virus (HIV) protease inhibitors, indinavir, saquinavir, ritonavir, amprenavir, nelfinavir and lopinavir, was developed and validated. Optimal separation was achieved on a PLRP-S 100 Å, 250 x 4.6 mm I.D. column maintained ...

  9. Analytical models approximating individual processes: a validation method.

    Science.gov (United States)

    Favier, C; Degallier, N; Menkès, C E

    2010-12-01

    Upscaling population models from fine to coarse resolutions, in space, time and/or level of description, allows the derivation of fast and tractable models based on a thorough knowledge of individual processes. The validity of such approximations is generally tested only on a limited range of parameter sets. A more general validation test, over a range of parameters, is proposed; this would estimate the error induced by the approximation, using the original model's stochastic variability as a reference. This method is illustrated by three examples taken from the field of epidemics transmitted by vectors that bite in a temporally cyclical pattern, that illustrate the use of the method: to estimate if an approximation over- or under-fits the original model; to invalidate an approximation; to rank possible approximations for their qualities. As a result, the application of the validation method to this field emphasizes the need to account for the vectors' biology in epidemic prediction models and to validate these against finer scale models. Copyright © 2010 Elsevier Inc. All rights reserved.

  10. Bioanalytical Chemistry of Cytokines-A Review

    Science.gov (United States)

    Stenken, Julie A.; Poschenrieder, Andreas J.

    2014-01-01

    Cytokines are bioactive proteins produced by many different cells of the immune system. Due to their role in different inflammatory disease states and maintaining homeostasis, there is enormous clinical interest in the quantitation of cytokines. The typical standard methods for quantitation of cytokines are immunoassay-based techniques including enzyme-linked immusorbent assays (ELISA) and bead-based immunoassays read by either standard or modified flow cytometers. A review of recent developments in analytical methods for measurements of cytokine proteins is provided. This review briefly covers cytokine biology and the analysis challenges associated with measurement of these biomarker proteins for understanding both health and disease. New techniques applied to immunoassay-based assays are presented along with the uses of aptamers, electrochemistry, mass spectrometry, optical resonator-based methods. Methods used for elucidating the release of cytokines from single cells as well as in vivo collection methods are described. PMID:25467452

  11. Cleaning validation of ofloxacin on pharmaceutical manufacturing equipment and validation of desired HPLC method.

    Science.gov (United States)

    Arayne, M Saeed; Sultana, Najma; Sajid, S Shahnawaz; Ali, S Shahid

    2008-01-01

    Inadequate cleaning of a pharmaceutical manufacturing plant or inadequate purging of the individual pieces of equipment used in multi-product manufacturing or equipment not dedicated to individual products may lead to contamination of the next batch of pharmaceutics manufactured using the same equipment. Challenges for cleaning validation are encountered especially when developing sensitive analytical methods capable of detecting traces of active pharmaceutical ingredients that are likely to remain on the surface of the pharmaceutical equipment after cleaning. A method's inability to detect some residuals could mean that either the method is not sensitive enough to the residue in question or the sampling procedure is inadequate. A sensitive and reproducible reversed-phase, high-performance liquid chromatographic method was developed for the determination of ofloxacin in swab samples. The method for determining ofloxacin residues on manufacturing equipment surfaces was validated in regard to precision, linearity, accuracy, specificity, limit of quantification, and percent recovery from the equipment surface, as well as the stability of a potential contaminant in a cleaning validation process. The active compound was selectively quantified in a sample matrix and swab material in amounts as low as 0.55 ng/mL. The swabbing procedure using cotton swabs was validated. A mean recovery from stainless steel plate of close to 85% was obtained. Chromatography was carried out on a pre-packed Merck (Dermstadt, Germany) Lichrospher model 100 Rp-18 (5.0 microm, 250 mm X 4.0 mm) column using a mixture of sodium lauryl sulfate (0.024% aqueous solution), acetonitrile, and glacial acetic acid (500:480:20,v/v) as the mobile phase at a flow rate of 1.5 mL/min with a column temperature of 35 degrees C and 294 nm detection. The assay was linear over the concentration range of 2 ng/mL to 2000 ng/mL (R approximately 0.99998). The method was validated for accuracy and precision. The

  12. Bioanalytical Experiments for the Undergraduate Laboratory: Monitoring Glucose in Sports Drinks

    Science.gov (United States)

    Gooding, J. Justin; Yang, Wenrong; Situmorang, Manihar

    2001-06-01

    This paper describes two complementary bioanalytical experiments for analyzing the concentration of glucose in sports drinks. The first experiment is a spectrophotometric enzyme assay employing the enzymes glucose oxidase (GOx) and horseradish peroxidase (HRP). The glucose is oxidized by the GOx, producing hydrogen peroxide, which is the substrate for HRP. In the reduction of the H2O2 a chromogen is oxidized, causing a color change. In the partner experiment, the GOx is immobilized on a platinum electrode using a dialysis membrane. The hydrogen peroxide produced in the enzyme reaction is monitored amperometrically by oxidizing the hydrogen peroxide produced. The simple method of preparing the enzyme electrode is useful in demonstrating the important parameters in defining the response of enzyme electrodes. The same sports drinks are analyzed in both experiments. The two experiments together illustrate the advantage of bioanalysis in analyzing complex samples with minimal sample preparation.

  13. Real Time Analysis of Bioanalytes in Healthcare, Food, Zoology and Botany.

    Science.gov (United States)

    Wang, Tianqi; Ramnarayanan, Ashwin; Cheng, Huanyu

    2017-12-21

    The growing demand for real time analysis of bioanalytes has spurred development in the field of wearable technology to offer non-invasive data collection at a low cost. The manufacturing processes for creating these sensing systems vary significantly by the material used, the type of sensors needed and the subject of study as well. The methods predominantly involve stretchable electronic sensors to monitor targets and transmit data mainly through flexible wires or short-range wireless communication devices. Capable of conformal contact, the application of wearable technology goes beyond the healthcare to fields of food, zoology and botany. With a brief review of wearable technology and its applications to various fields, we believe this mini review would be of interest to the reader in broad fields of materials, sensor development and areas where wearable sensors can provide data that are not available elsewhere.

  14. Methods for Geometric Data Validation of 3d City Models

    Science.gov (United States)

    Wagner, D.; Alam, N.; Wewetzer, M.; Pries, M.; Coors, V.

    2015-12-01

    Geometric quality of 3D city models is crucial for data analysis and simulation tasks, which are part of modern applications of the data (e.g. potential heating energy consumption of city quarters, solar potential, etc.). Geometric quality in these contexts is however a different concept as it is for 2D maps. In the latter case, aspects such as positional or temporal accuracy and correctness represent typical quality metrics of the data. They are defined in ISO 19157 and should be mentioned as part of the metadata. 3D data has a far wider range of aspects which influence their quality, plus the idea of quality itself is application dependent. Thus, concepts for definition of quality are needed, including methods to validate these definitions. Quality on this sense means internal validation and detection of inconsistent or wrong geometry according to a predefined set of rules. A useful starting point would be to have correct geometry in accordance with ISO 19107. A valid solid should consist of planar faces which touch their neighbours exclusively in defined corner points and edges. No gaps between them are allowed, and the whole feature must be 2-manifold. In this paper, we present methods to validate common geometric requirements for building geometry. Different checks based on several algorithms have been implemented to validate a set of rules derived from the solid definition mentioned above (e.g. water tightness of the solid or planarity of its polygons), as they were developed for the software tool CityDoctor. The method of each check is specified, with a special focus on the discussion of tolerance values where they are necessary. The checks include polygon level checks to validate the correctness of each polygon, i.e. closeness of the bounding linear ring and planarity. On the solid level, which is only validated if the polygons have passed validation, correct polygon orientation is checked, after self-intersections outside of defined corner points and edges

  15. Luminescent lanthanide reporters: new concepts for use in bioanalytical applications.

    Science.gov (United States)

    Vuojola, Johanna; Soukka, Tero

    2014-01-23

    Lanthanides represent the chemical elements from lanthanum to lutetium. They intrinsically exhibit some very exciting photophysical properties, which can be further enhanced by incorporating the lanthanide ion into organic or inorganic sensitizing structures. A very popular approach is to conjugate the lanthanide ion to an organic chromophore structure forming lanthanide chelates. Another approach, which has quickly gained interest, is to incorporate the lanthanide ions into nanoparticle structures, thus attaining improved specific activity and a large surface area for biomolecule immobilization. Lanthanide-based reporters, when properly shielded from the quenching effects of water, usually express strong luminescence emission, multiple narrow emission lines covering a wide wavelength range, and exceptionally long excited state lifetimes enabling time-gated luminescence detection. Because of these properties, lanthanide-based reporters have found widespread applications in various fields of life. This review focuses on the field of bioanalytical applications. Luminescent lanthanide reporters and assay formats utilizing these reporters pave the way for increasingly sensitive, simple, and easily automated bioanalytical applications.

  16. Luminescent lanthanide reporters: new concepts for use in bioanalytical applications

    International Nuclear Information System (INIS)

    Vuojola, Johanna; Soukka, Tero

    2014-01-01

    Lanthanides represent the chemical elements from lanthanum to lutetium. They intrinsically exhibit some very exciting photophysical properties, which can be further enhanced by incorporating the lanthanide ion into organic or inorganic sensitizing structures. A very popular approach is to conjugate the lanthanide ion to an organic chromophore structure forming lanthanide chelates. Another approach, which has quickly gained interest, is to incorporate the lanthanide ions into nanoparticle structures, thus attaining improved specific activity and a large surface area for biomolecule immobilization. Lanthanide-based reporters, when properly shielded from the quenching effects of water, usually express strong luminescence emission, multiple narrow emission lines covering a wide wavelength range, and exceptionally long excited state lifetimes enabling time-gated luminescence detection. Because of these properties, lanthanide-based reporters have found widespread applications in various fields of life. This review focuses on the field of bioanalytical applications. Luminescent lanthanide reporters and assay formats utilizing these reporters pave the way for increasingly sensitive, simple, and easily automated bioanalytical applications. (topical review)

  17. Shielding design method for LMFBR validation on the Phenix factor

    International Nuclear Information System (INIS)

    Cabrillat, J.C.; Crouzet, J.; Misrakis, J.; Salvatores, M.; Rado, V.; Palmiotti, G.

    1983-05-01

    Shielding design methods, developed at CEA for shielding calculations find a global validation by the means of Phenix power reactor (250 MWe) measurements. Particularly, the secondary sodium activation of pool type LMFBR such as Super Phenix (1200 MWe) which is subject to strict safety limitation is well calculated by the adapted scheme, i.e. a two dimension transport calculation of shielding coupled to a Monte-Carlo calculation of secondary sodium activation

  18. OWL-based reasoning methods for validating archetypes.

    Science.gov (United States)

    Menárguez-Tortosa, Marcos; Fernández-Breis, Jesualdo Tomás

    2013-04-01

    Some modern Electronic Healthcare Record (EHR) architectures and standards are based on the dual model-based architecture, which defines two conceptual levels: reference model and archetype model. Such architectures represent EHR domain knowledge by means of archetypes, which are considered by many researchers to play a fundamental role for the achievement of semantic interoperability in healthcare. Consequently, formal methods for validating archetypes are necessary. In recent years, there has been an increasing interest in exploring how semantic web technologies in general, and ontologies in particular, can facilitate the representation and management of archetypes, including binding to terminologies, but no solution based on such technologies has been provided to date to validate archetypes. Our approach represents archetypes by means of OWL ontologies. This permits to combine the two levels of the dual model-based architecture in one modeling framework which can also integrate terminologies available in OWL format. The validation method consists of reasoning on those ontologies to find modeling errors in archetypes: incorrect restrictions over the reference model, non-conformant archetype specializations and inconsistent terminological bindings. The archetypes available in the repositories supported by the openEHR Foundation and the NHS Connecting for Health Program, which are the two largest publicly available ones, have been analyzed with our validation method. For such purpose, we have implemented a software tool called Archeck. Our results show that around 1/5 of archetype specializations contain modeling errors, the most common mistakes being related to coded terms and terminological bindings. The analysis of each repository reveals that different patterns of errors are found in both repositories. This result reinforces the need for making serious efforts in improving archetype design processes. Copyright © 2012 Elsevier Inc. All rights reserved.

  19. Development and validation of a highly sensitive LC-ESI-MS/MS method for estimation of IIIM-MCD-211, a novel nitrofuranyl methyl piperazine derivative with potential activity against tuberculosis: Application to drug development.

    Science.gov (United States)

    Magotra, Asmita; Sharma, Anjna; Gupta, Ajai Prakash; Wazir, Priya; Sharma, Shweta; Singh, Parvinder Pal; Tikoo, Manoj Kumar; Vishwakarma, Ram A; Singh, Gurdarshan; Nandi, Utpal

    2017-08-15

    In the present study, a simple, sensitive, specific and rapid liquid chromatography (LC) tandem mass spectrometry (MS/MS) method was developed and validated according to the Food and Drug Administration (FDA) guidelines for estimation of IIIM-MCD-211 (a potent oral candidate with promising action against tuberculosis) in mice plasma using carbamazepine as internal standard (IS). Bioanalytical method consisted of one step protein precipitation for sample preparation followed by quantitation in LC-MS/MS using positive electrospray ionization technique (ESI) operating in multiple reaction monitoring (MRM) mode. Elution was achieved in gradient mode on High Resolution Chromolith RP-18e column with mobile phase comprised of acetonitrile and 0.1% (v/v) formic acid in water at the flow rate of 0.4mL/min. Precursor to product ion transitions (m/z 344.5/218.4 and m/z 237.3/194.2) were used to measure analyte and IS, respectively. All validation parameters were well within the limit of acceptance criteria. The method was successfully applied to assess the pharmacokinetics of the candidate in mice following oral (10mg/kg) and intravenous (IV; 2.5mg/kg) administration. It was also effectively used to quantitate metabolic stability of the compound in mouse liver microsomes (MLM) and human liver microsomes (HLM) followed by its in-vitro-in-vivo extrapolation. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Survey and assessment of conventional software verification and validation methods

    International Nuclear Information System (INIS)

    Miller, L.A.; Groundwater, E.; Mirsky, S.M.

    1993-04-01

    By means of a literature survey, a comprehensive set of methods was identified for the verification and validation of conventional software. The 134 methods so identified were classified according to their appropriateness for various phases of a developmental lifecycle -- requirements, design, and implementation; the last category was subdivided into two, static testing and dynamic testing methods. The methods were then characterized in terms of eight rating factors, four concerning ease-of-use of the methods and four concerning the methods' power to detect defects. Based on these factors, two measurements were developed to permit quantitative comparisons among methods, a Cost-Benefit metric and an Effectiveness Metric. The Effectiveness Metric was further refined to provide three different estimates for each method, depending on three classes of needed stringency of V ampersand V (determined by ratings of a system's complexity and required-integrity). Methods were then rank-ordered for each of the three classes in terms of their overall cost-benefits and effectiveness. The applicability was then assessed of each method for the four identified components of knowledge-based and expert systems, as well as the system as a whole

  1. Dependability validation by means of fault injection: method, implementation, application

    International Nuclear Information System (INIS)

    Arlat, Jean

    1990-01-01

    This dissertation presents theoretical and practical results concerning the use of fault injection as a means for testing fault tolerance in the framework of the experimental dependability validation of computer systems. The dissertation first presents the state-of-the-art of published work on fault injection, encompassing both hardware (fault simulation, physical fault Injection) and software (mutation testing) issues. Next, the major attributes of fault injection (faults and their activation, experimental readouts and measures, are characterized taking into account: i) the abstraction levels used to represent the system during the various phases of its development (analytical, empirical and physical models), and Il) the validation objectives (verification and evaluation). An evaluation method is subsequently proposed that combines the analytical modeling approaches (Monte Carlo Simulations, closed-form expressions. Markov chains) used for the representation of the fault occurrence process and the experimental fault Injection approaches (fault Simulation and physical injection); characterizing the error processing and fault treatment provided by the fault tolerance mechanisms. An experimental tool - MESSALINE - is then defined and presented. This tool enables physical faults to be Injected In an hardware and software prototype of the system to be validated. Finally, the application of MESSALINE for testing two fault-tolerant systems possessing very dissimilar features and the utilization of the experimental results obtained - both as design feedbacks and for dependability measures evaluation - are used to illustrate the relevance of the method. (author) [fr

  2. Plasmonic nanostructures for bioanalytical applications of SERS

    Science.gov (United States)

    Kahraman, Mehmet; Wachsmann-Hogiu, Sebastian

    2016-03-01

    Surface-enhanced Raman scattering (SERS) is a potential analytical technique for the detection and identification of chemicals and biological molecules and structures in the close vicinity of metallic nanostructures. We present a novel method to fabricate tunable plasmonic nanostructures and perform a comprehensive structural and optical characterization of the structures. Spherical latex particles are uniformly deposited on glass slides and used as templates to obtain nanovoid structures on polydimethylsiloxane surfaces. The diameter and depth of the nanovoids are controlled by the size of the latex particles. The nanovoids are coated with a thin Ag layer for fabrication of uniform plasmonic nanostructures. Structural characterization of the surfaces is performed by scanning electron microscopy (SEM) and atomic force microscopy (AFM). Optical properties of these plasmonic nanostructures are evaluated via UV/Vis spectroscopy, and SERS. The sample preparation step is the key point to obtain strong and reproducible SERS spectra from the biological structures. When the colloidal suspension is used as a SERS substrate for the protein detection, the electrostatic interaction of the proteins with the nanoparticles is described by the nature of their charge status, which influences the aggregation properties such as the size and shape of the aggregates, which is critical for the SERS experiment. However, when the solid SERS substrates are fabricated, SERS signal of the proteins that are background free and independent of the protein charge. Pros and cons of using plasmonic nano colloids and nanostructures as SERS substrate will be discussed for label-free detection of proteins using SERS.

  3. Validation of ultraviolet method to determine serum phosphorus level

    International Nuclear Information System (INIS)

    Garcia Borges, Lisandra; Perez Prieto, Teresa Maria; Valdes Diez, Lilliam

    2009-01-01

    Validation of a spectrophotometry method applicable in clinic labs was proposed to analytical assessment of serum phosphates using a kit UV-phosphorus of domestic production from 'Carlos J. Finlay' Biologics Production Enterprise (Havana, Cuba). Analysis method was based on phosphorus reaction to ammonium molybdenum to acid pH to creating a measurable complex to 340 nm. Specificity and precision were measured considering the method strength, linearity, accuracy and sensitivity. Analytical method was linear up to 4,8 mmol/L, precise (CV 30 .999) during clinical interest concentration interval where there were not interferences by matrix. Detection limit values were of 0.037 mmol/L and of quantification of 0.13 mmol/L both were satisfactory for product use

  4. Methods and practices for verification and validation of programmable systems

    International Nuclear Information System (INIS)

    Heimbuerger, H.; Haapanen, P.; Pulkkinen, U.

    1993-01-01

    The programmable systems deviate by their properties and behaviour from the conventional non-programmable systems in such extent, that their verification and validation for safety critical applications requires new methods and practices. The safety assessment can not be based on conventional probabilistic methods due to the difficulties in the quantification of the reliability of the software and hardware. The reliability estimate of the system must be based on qualitative arguments linked to a conservative claim limit. Due to the uncertainty of the quantitative reliability estimate other means must be used to get more assurance about the system safety. Methods and practices based on research done by VTT for STUK, are discussed in the paper as well as the methods applicable in the reliability analysis of software based safety functions. The most essential concepts and models of quantitative reliability analysis are described. The application of software models in probabilistic safety analysis (PSA) is evaluated. (author). 18 refs

  5. Validated spectrophotometric methods for determination of some oral hypoglycemic drugs.

    Science.gov (United States)

    Farouk, M; Abdel-Satar, O; Abdel-Aziz, O; Shaaban, M

    2011-02-01

    Four accurate, precise, rapid, reproducible, and simple spectrophotometric methods were validated for determination of repaglinide (RPG), pioglitazone hydrochloride (PGL) and rosiglitazone maleate (RGL). The first two methods were based on the formation of a charge-transfer purple-colored complex of chloranilic acid with RPG and RGL with a molar absorptivity 1.23 × 103 and 8.67 × 102 l•mol-1•cm-1 and a Sandell's sensitivity of 0.367 and 0.412 μg•cm-2, respectively, and an ion-pair yellow-colored complex of bromophenol blue with RPG, PGL and RGL with molar absorptivity 8.86 × 103, 6.95 × 103, and 7.06 × 103 l•mol-1•cm-1, respectively, and a Sandell's sensitivity of 0.051 μg•cm-2 for all ion-pair complexes. The influence of different parameters on color formation was studied to determine optimum conditions for the visible spectrophotometric methods. The other spectrophotometric methods were adopted for demtermination of the studied drugs in the presence of their acid-, alkaline- and oxidative-degradates by computing derivative and pH-induced difference spectrophotometry, as stability-indicating techniques. All the proposed methods were validated according to the International Conference on Harmonization guidelines and successfully applied for determination of the studied drugs in pure form and in pharmaceutical preparations with good extraction recovery ranges between 98.7-101.4%, 98.2-101.3%, and 99.9-101.4% for RPG, PGL, and RGL, respectively. Results of relative standard deviations did not exceed 1.6%, indicating that the proposed methods having good repeatability and reproducibility. All the obtained results were statistically compared to the official method used for RPG analysis and the manufacturers methods used for PGL and RGL analysis, respectively, where no significant differences were found.

  6. A Simple HPLC Bioanalytical Method for the Determination of ...

    African Journals Online (AJOL)

    reversed-phase HPLC column. Following protein precipitation extraction, .... The criteria for acceptability of the data include accuracy within ± 15 % of the coefficient of variation (CV) from the nominal values and a precision of within. ± 15 % of the coefficient of variation (CV) ... four-fold with blank plasma. The diluted samples.

  7. Validated HPTLC method of analysis for artemether and its formulations.

    Science.gov (United States)

    Tayade, Nitin G; Nagarsenker, Mangal S

    2007-02-19

    A simple, sensitive, precise and rapid high-performance thin-layer chromatographic (HPTLC) method of analysis for artemether both as a bulk drug and in pharmaceutical formulations was developed and validated. The method employed TLC aluminum plates precoated with silica gel 60F-254 as the stationary phase. The solvent system consisted of toluene-ethyl acetate-formic acid (8:2:0.3, v/v/v) as mobile phase. Densitometric analysis of artemether was carried out in the reflectance mode at 565 nm. The system was found to give compact spots for artemether (R(f) value of 0.50+/-0.03). The linear regression analysis data for the calibration plots showed good linear relationship with r(2)=0.9904 in the concentration range 200-1000 ng per spot. The mean value of correlation coefficient, slope and intercept were 0.9904+/-0.011, 7.27+/-0.11 and 166.24+/-56.92, respectively. The method was validated for precision, accuracy, recovery and robustness. The limits of detection and quantitation were 65.91 and 197.74 ng per spot, respectively. The method has been successfully applied in the analysis of lipid based parenteral formulations and marketed oral solid dosage formulation.

  8. Validation method training: nurses' experiences and ratings of work climate.

    Science.gov (United States)

    Söderlund, Mona; Norberg, Astrid; Hansebo, Görel

    2014-03-01

    Training nursing staff in communication skills can impact on the quality of care for residents with dementia and contributes to nurses' job satisfaction. Changing attitudes and practices takes time and energy and can affect the entire nursing staff, not just the nurses directly involved in a training programme. Therefore, it seems important to study nurses' experiences of a training programme and any influence of the programme on work climate among the entire nursing staff. To explore nurses' experiences of a 1-year validation method training programme conducted in a nursing home for residents with dementia and to describe ratings of work climate before and after the programme. A mixed-methods approach. Twelve nurses participated in the training and were interviewed afterwards. These individual interviews were tape-recorded and transcribed, then analysed using qualitative content analysis. The Creative Climate Questionnaire was administered before (n = 53) and after (n = 56) the programme to the entire nursing staff in the participating nursing home wards and analysed with descriptive statistics. Analysis of the interviews resulted in four categories: being under extra strain, sharing experiences, improving confidence in care situations and feeling uncertain about continuing the validation method. The results of the questionnaire on work climate showed higher mean values in the assessment after the programme had ended. The training strengthened the participating nurses in caring for residents with dementia, but posed an extra strain on them. These nurses also described an extra strain on the entire nursing staff that was not reflected in the results from the questionnaire. The work climate at the nursing home wards might have made it easier to conduct this extensive training programme. Training in the validation method could develop nurses' communication skills and improve their handling of complex care situations. © 2013 Blackwell Publishing Ltd.

  9. Validation of spectrophotometric method for lactulose assay in syrup preparation

    Science.gov (United States)

    Mahardhika, Andhika Bintang; Novelynda, Yoshella; Damayanti, Sophi

    2015-09-01

    Lactulose is a synthetic disaccharide widely used in food and pharmaceutical fields. In the pharmaceutical field, lactulose is used as osmotic laxative in a syrup dosage form. This research was aimed to validate the spectrophotometric method to determine the levels of lactulose in syrup preparation and the commercial sample. Lactulose is hydrolyzed by hydrochloric acid to form fructose and galactose. The fructose was reacted with resorcinol reagent, forming compounds that give absorption peak at 485 nm. Analytical methods was validated, hereafter lactulose content in syrup preparation were determined. The calibration curve was linear in the range of 30-100 μg/mL with a correlation coefficient (r) of 0.9996, coefficient of variance (Vxo) of 1.1 %, limit of detection of 2.32 μg/mL, and limit of quantitation of 7.04 μg/mL. The result of accuracy test for the lactulose assay in the syrup preparation showed recoveries of 96.6 to 100.8 %. Repeatability test of lactulose assay in standard solution of lactulose and sample preparation syrup showed the coefficient of variation (CV) of 0.75 % and 0.7 %. Intermediate precision (interday) test resulted in coefficient of variation 1.06 % on the first day, the second day by 0.99 %, and 0.95 % for the third day. This research gave a valid analysis method and levels of lactulose in syrup preparations of samples A, B, C were 101.6, 100.5, and 100.6 %, respectively.

  10. Simulation Methods and Validation Criteria for Modeling Cardiac Ventricular Electrophysiology.

    Science.gov (United States)

    Krishnamoorthi, Shankarjee; Perotti, Luigi E; Borgstrom, Nils P; Ajijola, Olujimi A; Frid, Anna; Ponnaluri, Aditya V; Weiss, James N; Qu, Zhilin; Klug, William S; Ennis, Daniel B; Garfinkel, Alan

    2014-01-01

    We describe a sequence of methods to produce a partial differential equation model of the electrical activation of the ventricles. In our framework, we incorporate the anatomy and cardiac microstructure obtained from magnetic resonance imaging and diffusion tensor imaging of a New Zealand White rabbit, the Purkinje structure and the Purkinje-muscle junctions, and an electrophysiologically accurate model of the ventricular myocytes and tissue, which includes transmural and apex-to-base gradients of action potential characteristics. We solve the electrophysiology governing equations using the finite element method and compute both a 6-lead precordial electrocardiogram (ECG) and the activation wavefronts over time. We are particularly concerned with the validation of the various methods used in our model and, in this regard, propose a series of validation criteria that we consider essential. These include producing a physiologically accurate ECG, a correct ventricular activation sequence, and the inducibility of ventricular fibrillation. Among other components, we conclude that a Purkinje geometry with a high density of Purkinje muscle junctions covering the right and left ventricular endocardial surfaces as well as transmural and apex-to-base gradients in action potential characteristics are necessary to produce ECGs and time activation plots that agree with physiological observations.

  11. Simulation Methods and Validation Criteria for Modeling Cardiac Ventricular Electrophysiology.

    Directory of Open Access Journals (Sweden)

    Shankarjee Krishnamoorthi

    Full Text Available We describe a sequence of methods to produce a partial differential equation model of the electrical activation of the ventricles. In our framework, we incorporate the anatomy and cardiac microstructure obtained from magnetic resonance imaging and diffusion tensor imaging of a New Zealand White rabbit, the Purkinje structure and the Purkinje-muscle junctions, and an electrophysiologically accurate model of the ventricular myocytes and tissue, which includes transmural and apex-to-base gradients of action potential characteristics. We solve the electrophysiology governing equations using the finite element method and compute both a 6-lead precordial electrocardiogram (ECG and the activation wavefronts over time. We are particularly concerned with the validation of the various methods used in our model and, in this regard, propose a series of validation criteria that we consider essential. These include producing a physiologically accurate ECG, a correct ventricular activation sequence, and the inducibility of ventricular fibrillation. Among other components, we conclude that a Purkinje geometry with a high density of Purkinje muscle junctions covering the right and left ventricular endocardial surfaces as well as transmural and apex-to-base gradients in action potential characteristics are necessary to produce ECGs and time activation plots that agree with physiological observations.

  12. Validation of screening method for determination of methyltestosterone in fish

    Directory of Open Access Journals (Sweden)

    Stojkovski Velimir

    2013-07-01

    Full Text Available Anabolic androgenic steroids are synthetic derivatives of testosterone, which is the primary male sex hormone. These anabolic agents are used to increase the weight gain, to improve the food efficiency, storing proteins and to decrease fatness. However, depending on the use of anabolic agent in animal feed, anabolic residues that may occur in meat and meat products present risks to human health. The aim of this study was the validation of screening ELISA method for determination of methyltestoterone anabolic steroid in fish. The validation process was carried out according to Commission Decision 2002/657/EC criteria. The detection limit for methyltestosterone was 140.95 ng/kg and the detection capability was 564.43 ng/kg. The overall recoveries and the coefficients of variation (CV were in the range of 82.4%-97.4% and 1.5%-6.9%, respectively, a working range between 50 to 4050 ng/kg, and the regression equation of the final inhibition curve was: y= -0,1741x + 1,5082, R2 = 0.9927. Because of the good recovery and precision, and satisfactory detection capability, this method is applicable in official control laboratories as a rapid screening method for determination of methyltestosterone in fish.

  13. Laboratory diagnostic methods, system of quality and validation

    Directory of Open Access Journals (Sweden)

    Ašanin Ružica

    2005-01-01

    Full Text Available It is known that laboratory investigations secure safe and reliable results that provide a final confirmation of the quality of work. Ideas, planning, knowledge, skills, experience, and environment, along with good laboratory practice, quality control and reliability of quality, make the area of biological investigations very complex. In recent years, quality control, including the control of work in the laboratory, is based on international standards and is used at that level. The implementation of widely recognized international standards, such as the International Standard ISO/IEC 17025 (1 and the implementing of the quality system series ISO/IEC 9000 (2 have become the imperative on the grounds of which laboratories have a formal, visible and corresponding system of quality. The diagnostic methods that are used must constantly yield results which identify the animal as positive or negative, and the precise status of the animal is determined with a predefined degree of statistical significance. Methods applied on a selected population reduce the risk of obtaining falsely positive or falsely negative results. A condition for this are well conceived and documented methods, with the application of the corresponding reagents, and work with professional and skilled staff. This process requires also a consistent implementation of the most rigorous experimental plans, epidemiological and statistical data and estimations, with constant monitoring of the validity of the applied methods. Such an approach is necessary in order to cut down the number of misconceptions and accidental mistakes, for a referent population of animals on which the validity of a method is tested. Once a valid method is included in daily routine investigations, it is necessary to apply constant monitoring for the purpose of internal quality control, in order adequately to evaluate its reproducibility and reliability. Consequently, it is necessary at least twice yearly to conduct

  14. Surface-enhanced Raman spectroscopy bioanalytical, biomolecular and medical applications

    CERN Document Server

    Procházka, Marek

    2016-01-01

    This book gives an overview of recent developments in RS and SERS for sensing and biosensing considering also limitations, possibilities and prospects of this technique. Raman scattering (RS) is a widely used vibrational technique providing highly specific molecular spectral patterns. A severe limitation for the application of this spectroscopic technique lies in the low cross section of RS. Surface-enhanced Raman scattering (SERS) spectroscopy overcomes this problem by 6-11 orders of magnitude enhancement compared with the standard RS for molecules in the close vicinity of certain rough metal surfaces. Thus, SERS combines molecular fingerprint specificity with potential single-molecule sensitivity. Due to the recent development of new SERS-active substrates, labeling and derivatization chemistry as well as new instrumentations, SERS became a very promising tool for many varied applications, including bioanalytical studies and sensing. Both intrinsic and extrinsic SERS biosensing schemes have been employed to...

  15. 16th Annual Land O'Lakes Bioanalytical Conference.

    Science.gov (United States)

    Burns, Erik C; Guthrie, Randall H; Fluhler, Eric N; Stubbs, R John; Bateman, Kevin; King, Lindsay; Moran, Jeffrey

    2015-11-01

    This Land O'Lakes Conference is presented each year by the Division of Pharmacy Professional Development within the School of Pharmacy at the University of Wisconsin-Madison (USA). The purpose of this 3-day conference is to provide an educational forum to discuss issues and applications associated with the analysis of xenobiotics, metabolites, biologics and biomarkers in biological matrices. The conference is designed to include and encourage an open exchange of scientific and methodological applications for bioanalysis. To increase the interactive nature of the conference, the program is a mixture of lectures, interactive discussions and a poster session. This report summarized the presentations at the 16th Annual Conference. 6th Annual Land O'Lakes Bioanalytical Conference, Fluno Center Madison, WI, USA, 13-16 July 2015.

  16. Validation study of core analysis methods for full MOX BWR

    International Nuclear Information System (INIS)

    2013-01-01

    JNES has been developing a technical database used in reviewing validation of core analysis methods of LWRs in the coming occasions: (1) confirming the core safety parameters of the initial core (one-third MOX core) through a full MOX core in Oma Nuclear Power Plant, which is under the construction, (2) licensing high-burnup MOX cores in the future and (3) reviewing topical reports on core analysis codes for safety design and evaluation. Based on the technical database, JNES will issue a guide of reviewing the core analysis methods used for safety design and evaluation of LWRs. The database will be also used for validation and improving of core analysis codes developed by JNES. JNES has progressed with the projects: (1) improving a Doppler reactivity analysis model in a Monte Carlo calculation code MVP, (2) sensitivity study of nuclear cross section date on reactivity calculation of experimental cores composed of UO 2 and MOX fuel rods, (3) analysis of isotopic composition data for UO 2 and MOX fuels and (4) the guide of reviewing the core analysis codes and others. (author)

  17. Analytical methods validation of processes control in injectable antitumor agents

    International Nuclear Information System (INIS)

    Garcia Penna, Caridad Margarita; Cunill Semanat, Edel; Cartaya Morales, Mayra; Diaz de Arma, Anyisela; Curbelo Fonte, Yusleydis

    2010-01-01

    Alternative analytical methods were validated for the process control of 500 mg florouacil, 50 mg doxorrubicin and 50 mg methotrexate by spectrophotometry because of they are more simple and economic allowint to control the drugs quality in process analysis control. Calibration curves of fluorouracil, doxorrubicin and methotrexate were plotted in interval from 60 to 140%, where there were linear with correlation coefficients similar to 0.9998, 0.9999 and 0.9999, respectively; statistical text for intercept and slope were considered as non-significant. Recoveries of 99.97, 99.98 and 99.35% were achieved, respectively in study concentration interval and Cochran and t-Student tests were also non-significant. Methods were specific, linear, precises and exacts in interval of study concentrations

  18. Validation of a Rapid and Sensitive UPLC-MS-MS Method Coupled with Protein Precipitation for the Simultaneous Determination of Seven Pyrethroids in 100 µL of Rat Plasma by Using Ammonium Adduct as Precursor Ion.

    Science.gov (United States)

    Singh, Sheelendra Pratap; Dwivedi, Nistha; Raju, Kanumuri Siva Rama; Taneja, Isha; Wahajuddin, Mohammad

    2016-04-01

    United States Environmental Protection Agency has recommended estimating pyrethroids' risk using cumulative exposure. For cumulative risk assessment, it would be useful to have a bioanalytical method for quantification of one or several pyrethroids simultaneously in a small sample volume to support toxicokinetic studies. Therefore, in the present study, a simple, sensitive and high-throughput ultraperformance liquid chromatography-tandem mass spectrometry method was developed and validated for simultaneous analysis of seven pyrethroids (fenvalerate, fenpropathrin, bifenthrin, lambda-cyhalothrin, cyfluthrin, cypermethrin and deltamethrin) in 100 µL of rat plasma. A simple single-step protein precipitation method was used for the extraction of target compounds. The total chromatographic run time of the method was 5 min. The chromatographic system used a Supelco C18 column and isocratic elution with a mobile phase consisting of methanol and 5 mM ammonium formate in the ratio of 90 : 10 (v/v). Mass spectrometer (API 4000) was operated in multiple reaction monitoring positive-ion mode using the electrospray ionization technique. The calibration curves were linear in the range of 7.8-2,000 ng/mL with correlation coefficients of ≥ 0.99. All validation parameters such as precision, accuracy, recovery, matrix effect and stability met the acceptance criteria according to the regulatory guidelines. The method was successfully applied to the toxicokinetic study of cypermethrin in rats. To the best of our knowledge, this is the first LC-MS-MS method for the simultaneous analysis of pyrethroids in rat plasma. This validated method with minimal modification can also be utilized for forensic and clinical toxicological applications due to its simplicity, sensitivity and rapidity. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  19. Validation of a Rapid and Sensitive UPLC–MS-MS Method Coupled with Protein Precipitation for the Simultaneous Determination of Seven Pyrethroids in 100 µL of Rat Plasma by Using Ammonium Adduct as Precursor Ion

    Science.gov (United States)

    Singh, Sheelendra Pratap; Dwivedi, Nistha; Raju, Kanumuri Siva Rama; Taneja, Isha; Wahajuddin, Mohammad

    2016-01-01

    United States Environmental Protection Agency has recommended estimating pyrethroids’ risk using cumulative exposure. For cumulative risk assessment, it would be useful to have a bioanalytical method for quantification of one or several pyrethroids simultaneously in a small sample volume to support toxicokinetic studies. Therefore, in the present study, a simple, sensitive and high-throughput ultraperformance liquid chromatography–tandem mass spectrometry method was developed and validated for simultaneous analysis of seven pyrethroids (fenvalerate, fenpropathrin, bifenthrin, lambda-cyhalothrin, cyfluthrin, cypermethrin and deltamethrin) in 100 µL of rat plasma. A simple single-step protein precipitation method was used for the extraction of target compounds. The total chromatographic run time of the method was 5 min. The chromatographic system used a Supelco C18 column and isocratic elution with a mobile phase consisting of methanol and 5 mM ammonium formate in the ratio of 90 : 10 (v/v). Mass spectrometer (API 4000) was operated in multiple reaction monitoring positive-ion mode using the electrospray ionization technique. The calibration curves were linear in the range of 7.8–2,000 ng/mL with correlation coefficients of ≥0.99. All validation parameters such as precision, accuracy, recovery, matrix effect and stability met the acceptance criteria according to the regulatory guidelines. The method was successfully applied to the toxicokinetic study of cypermethrin in rats. To the best of our knowledge, this is the first LC–MS-MS method for the simultaneous analysis of pyrethroids in rat plasma. This validated method with minimal modification can also be utilized for forensic and clinical toxicological applications due to its simplicity, sensitivity and rapidity. PMID:26801239

  20. Validation of internal dosimetry protocols based on stochastic method

    International Nuclear Information System (INIS)

    Mendes, Bruno M.; Fonseca, Telma C.F.; Almeida, Iassudara G.; Trindade, Bruno M.; Campos, Tarcisio P.R.

    2015-01-01

    Computational phantoms adapted to Monte Carlo codes have been applied successfully in radiation dosimetry fields. NRI research group has been developing Internal Dosimetry Protocols - IDPs, addressing distinct methodologies, software and computational human-simulators, to perform internal dosimetry, especially for new radiopharmaceuticals. Validation of the IDPs is critical to ensure the reliability of the simulations results. Inter comparisons of data from literature with those produced by our IDPs is a suitable method for validation. The aim of this study was to validate the IDPs following such inter comparison procedure. The Golem phantom has been reconfigured to run on MCNP5. The specific absorbed fractions (SAF) for photon at 30, 100 and 1000 keV energies were simulated based on the IDPs and compared with reference values (RV) published by Zankl and Petoussi-Henss, 1998. The SAF average differences from RV and those obtained in IDP simulations was 2.3 %. The SAF largest differences were found in situations involving low energy photons at 30 keV. The Adrenals and thyroid, i.e. the lowest mass organs, had the highest SAF discrepancies towards RV as 7.2 % and 3.8 %, respectively. The statistic differences of SAF applying our IDPs from reference values were considered acceptable at the 30, 100 and 1000 keV spectra. We believe that the main reason for the discrepancies in IDPs run, found in lower masses organs, was due to our source definition methodology. Improvements of source spatial distribution in the voxels may provide outputs more consistent with reference values for lower masses organs. (author)

  1. Validation of internal dosimetry protocols based on stochastic method

    Energy Technology Data Exchange (ETDEWEB)

    Mendes, Bruno M.; Fonseca, Telma C.F., E-mail: bmm@cdtn.br [Centro de Desenvolvimento da Tecnologia Nuclear (CDTN/CNEN-MG), Belo Horizonte, MG (Brazil); Almeida, Iassudara G.; Trindade, Bruno M.; Campos, Tarcisio P.R., E-mail: tprcampos@yahoo.com.br [Universidade Federal de Minas Gerais (DEN/UFMG), Belo Horizonte, MG (Brazil). Departamento de Engenharia Nuclear

    2015-07-01

    Computational phantoms adapted to Monte Carlo codes have been applied successfully in radiation dosimetry fields. NRI research group has been developing Internal Dosimetry Protocols - IDPs, addressing distinct methodologies, software and computational human-simulators, to perform internal dosimetry, especially for new radiopharmaceuticals. Validation of the IDPs is critical to ensure the reliability of the simulations results. Inter comparisons of data from literature with those produced by our IDPs is a suitable method for validation. The aim of this study was to validate the IDPs following such inter comparison procedure. The Golem phantom has been reconfigured to run on MCNP5. The specific absorbed fractions (SAF) for photon at 30, 100 and 1000 keV energies were simulated based on the IDPs and compared with reference values (RV) published by Zankl and Petoussi-Henss, 1998. The SAF average differences from RV and those obtained in IDP simulations was 2.3 %. The SAF largest differences were found in situations involving low energy photons at 30 keV. The Adrenals and thyroid, i.e. the lowest mass organs, had the highest SAF discrepancies towards RV as 7.2 % and 3.8 %, respectively. The statistic differences of SAF applying our IDPs from reference values were considered acceptable at the 30, 100 and 1000 keV spectra. We believe that the main reason for the discrepancies in IDPs run, found in lower masses organs, was due to our source definition methodology. Improvements of source spatial distribution in the voxels may provide outputs more consistent with reference values for lower masses organs. (author)

  2. Oxcarbazepine: validation and application of an analytical method

    Directory of Open Access Journals (Sweden)

    Paula Cristina Rezende Enéas

    2010-06-01

    Full Text Available Oxcarbazepine (OXC is an important anticonvulsant and mood stabilizing drug. A pharmacopoeial monograph for OXC is not yet available and therefore the development and validation of a new analytical method for quantification of this drug is essential. In the present study, a UV spectrophotometric method for the determination of OXC was developed. The various parameters, such as linearity, precision, accuracy and specificity, were studied according to International Conference on Harmonization Guidelines. Batches of 150 mg OXC capsules were prepared and analyzed using the validated UV method. The formulations were also evaluated for parameters including drug-excipient compatibility, flowability, uniformity of weight, disintegration time, assay, uniformity of content and the amount of drug dissolved during the first hour.Oxcarbazepina (OXC é um fármaco anticonvulsivante e estabilizante do humor. O desenvolvimento e validação de método analítico para quantificação da OXC são de fundamental importância devido à ausência de monografias farmacopéicas oficiais para esse fármaco. Nesse trabalho, um método espectrofotométrico UV para determinação da OXC foi desenvolvido. O método proposto foi validado seguindo os parâmetros de linearidade, precisão, exatidão e especificidade de acordo com as normas da Conferência Internacional de Harmonização. Cápsulas de OXC 150 mg foram preparadas e analisadas utilizando-se o método analítico validado. As formulações foram avaliadas com relação à compatibilidade fármaco-excipientes, fluidez, determinação de peso, tempo de desintegração, doseamento, uniformidade de conteúdo e quantidade do fármaco dissolvido após 60 minutos.

  3. Application of the contour method to validate residual stress predictions

    International Nuclear Information System (INIS)

    Welding is the most widespread method employed to join metallic components in nuclear power plants. This is an aggressive process that introduces complex three-dimensional residual stresses of substantial magnitude into engineering components. For safety-critical applications it can be of crucial importance to have an accurate characterisation of the residual stress field present in order to assess plant lifetime and risk of failure. Finite element modelling approaches are being increasingly employed by engineers to predict welding residual stresses. However, such predictions are challenging owing to the innate complexity of the welding process and can give highly variable results. Therefore, it is always desirable to validate residual stress predictions by experimental data. This paper illustrates how the contour method of measuring residual stress can be applied to various weldments in order to provide high quality experimental data. The contour method results are compared with data obtained by other well-established residual stress measurement techniques such as neutron diffraction and slitting methods and show a very satisfactory correlation. (author)

  4. Validation of EORTC IN-PATSAT 32 in Morocco: Methods

    Science.gov (United States)

    Obtel, Majdouline; Serhier, Zineb; Bendahhou, Karima; Bennani, Maria; Zidouh, Ahmed; Benider, Abdellatif; Errihani, Hassan; Bekkali, Rachid; Nejjari, Chakib

    2017-05-01

    Background. The EORTC IN-PATSAT32 questionnaire was developed by the EORTC Quality of Life (QL) Group to assess the satisfaction of patients affected by cancer and hospitalized in oncology centers. The aim of this study is to assess the psychometric properties of the EORTC IN-PATSAT32 administered to Moroccan patients. Methods. A total of 133 hospitalized patients affected by cancer in different sites completed the translated EORTC IN-PATSAT32 questionnaire in oncology hospitals. The internal consistence reliability, reproducibility and construct validity were assessed. Results. The homogeneity was good for all scales with Cronbach’s coefficients from 0.72 to 0.95 for all scales. Reproducibility test-retest was very satisfactory and the intra-class correlations coefficients (ICCs) for the scales were all above 0.70 except for the single general satisfaction with a ICC of 0.67. All items were highly correlated with own rather than other scales. Conclusion. The results of this study confirm that the Moroccan Arabic version of the EORTC IN-PATSAT32 has acceptable reliability and validity, comparable to those reported for other languages. Creative Commons Attribution License

  5. Increasing bioanalytical throughput using pcSFC-MS/MS: 10 minutes per 96-well plate.

    Science.gov (United States)

    Hoke, S H; Tomlinson, J A; Bolden, R D; Morand, K L; Pinkston, J D; Wehmeyer, K R

    2001-07-01

    The utility of packed-column supercritical, subcritical, and enhanced fluidity liquid chromatographies (pcSFC) for high-throughput applications has increased during the past few years. In contrast to traditional reversed-phase liquid chromatography, the addition of a volatile component to the mobile phase, such as CO2, produces a lower mobile-phase viscosity. This allows the use of higher flow rates which can translate into faster analysis times. In addition, the resulting mobile phase is considerably more volatile than the aqueous-based mobile phases that are typically used with LC-MS, allowing the entire effluent to be directed into the MS interface. High-throughput bioanalytical quantitation using pcSFC-MS/MS for pharmacokinetics applications is demonstrated in this report using dextromethorphan as a model compound. Plasma samples were prepared by automated liquid/liquid extraction in the 96-well format prior to pcSFC-MS/MS analysis. Three days of validation data are provided along with study sample data from a patient dosed with commercially available Vicks 44. Using pcSFC and MS/MS, dextromethorphan was quantified in 96-well plates at a rate of approximately 10 min/plate with average intraday accuracy of 9% or better. Daily relative standard deviations (RSDs) were less than 10% for the 2.21 and 14.8 ng/mL quality control (QC) samples, while the RSDs were less than 15% at the 0.554 ng/mL QC level.

  6. Evaluation of methods used for estimating content validity.

    Science.gov (United States)

    Almanasreh, Enas; Moles, Rebekah; Chen, Timothy F

    2018-03-27

    The assessment of content validity is a critical and complex step in the development process of instruments which are frequently used to measure complex constructs in social and administrative pharmacy research. The aims of this study were to investigate the elements of content validity; to describe a practical approach for assessing content validity; and to discuss existing content validity indices. This is a narrative review of the assessment and quantification of content validity. It describes the key stages of conducting the content validation study and discusses the quantification and evaluation of the content validity estimates. Content validity provides evidence about the degree to which elements of an assessment instrument are relevant to and representative of the targeted construct for a particular assessment purpose. The assessment of content validity relies on using a panel of experts to evaluate instrument elements and rate them based on their relevance and representativeness to the content domain. It is a three-stage process that includes; the development stage, judgment and quantifying stage, and revising and reconstruction stage. To quantify the expert judgments, several indices have been discussed in this paper such as the content validity ratio (CVR), content validity index (CVI), modified-Kappa, and some agreement indices. A practical guide describes the process of content validity evaluation is provided. In summary, content validation processes and content validity indices are essential factors in the instrument development process, should be treated and reported as important as other types of construct validation. Determining item CVI and reporting an overall CVI are important components necessary to instruments especially when the instrument is used to measure health outcomes or to guide a clinical decision making. Content validity deserves a rigorous assessment process as the obtained information from this process are invaluable for the

  7. Method for Determining Volumetric Efficiency and Its Experimental Validation

    Directory of Open Access Journals (Sweden)

    Ambrozik Andrzej

    2017-12-01

    Full Text Available Modern means of transport are basically powered by piston internal combustion engines. Increasingly rigorous demands are placed on IC engines in order to minimise the detrimental impact they have on the natural environment. That stimulates the development of research on piston internal combustion engines. The research involves experimental and theoretical investigations carried out using computer technologies. While being filled, the cylinder is considered to be an open thermodynamic system, in which non-stationary processes occur. To make calculations of thermodynamic parameters of the engine operating cycle, based on the comparison of cycles, it is necessary to know the mean constant value of cylinder pressure throughout this process. Because of the character of in-cylinder pressure pattern and difficulties in pressure experimental determination, in the present paper, a novel method for the determination of this quantity was presented. In the new approach, the iteration method was used. In the method developed for determining the volumetric efficiency, the following equations were employed: the law of conservation of the amount of substance, the first law of thermodynamics for open system, dependences for changes in the cylinder volume vs. the crankshaft rotation angle, and the state equation. The results of calculations performed with this method were validated by means of experimental investigations carried out for a selected engine at the engine test bench. A satisfactory congruence of computational and experimental results as regards determining the volumetric efficiency was obtained. The method for determining the volumetric efficiency presented in the paper can be used to investigate the processes taking place in the cylinder of an IC engine.

  8. A new method for analysis of underivatized free β-methylamino-alanine: Validation and method comparison.

    Science.gov (United States)

    Rosén, Johan; Westerberg, Erik; Hellenäs, Karl-Erik; Salomonsson, Matilda L

    2016-10-01

    A new method was developed for analysis of free β-Methylamino-alanine (BMAA) in biological matrices. The method is based on direct analysis of the underivatized molecule, using an amide column for separation by Hydrophilic Interaction Liquid Chromatography (HILIC) and detection by tandem mass spectrometry (MS/MS) using a deuterium labeled internal standard. The use of Ultra-High Performance Liquid Chromatography (UHPLC) combined with MS/MS detection allowed for high chromatographic resolution and a low limit of detection (0.025 μg/g wet weight (ww) in mussels). The method was validated by analyzing spiked blank mussels from the Baltic Sea (0.15-4.4 μg/g (ww), trueness 99%-105%, RSD 2%-8%). An inter-laboratory comparative analysis of extracts of mussel was performed. The mussels were extracted according to an established protocol for analysis of free BMAA, and the extracts were then analyzed in parallel by the new method and a validated procedure based on detection of BMAA derivatized with dansyl chloride. Both methods detected BMAA in similar concentrations. Thus, derivatization with dansyl chloride did not influence the results compared to direct detection. The new method presents an alternative to the commonly applied derivatization step, and is proved through validation and method comparison to reliably identify and quantify free BMAA at low concentration levels. Copyright © 2016 Elsevier Ltd. All rights reserved.

  9. Teaching Analytical Method Transfer through Developing and Validating Then Transferring Dissolution Testing Methods for Pharmaceuticals

    Science.gov (United States)

    Kimaru, Irene; Koether, Marina; Chichester, Kimberly; Eaton, Lafayette

    2017-01-01

    Analytical method transfer (AMT) and dissolution testing are important topics required in industry that should be taught in analytical chemistry courses. Undergraduate students in senior level analytical chemistry laboratory courses at Kennesaw State University (KSU) and St. John Fisher College (SJFC) participated in development, validation, and…

  10. New validated method for piracetam HPLC determination in human plasma.

    Science.gov (United States)

    Curticapean, Augustin; Imre, Silvia

    2007-01-10

    The new method for HPLC determination of piracetam in human plasma was developed and validated by a new approach. The simple determination by UV detection was performed on supernatant, obtained from plasma, after proteins precipitation with perchloric acid. The chromatographic separation of piracetam under a gradient elution was achieved at room temperature with a RP-18 LiChroSpher 100 column and aqueous mobile phase containing acetonitrile and methanol. The quantitative determination of piracetam was performed at 200 nm with a lower limit of quantification LLQ=2 microg/ml. For this limit, the calculated values of the coefficient of variation and difference between mean and the nominal concentration are CV%=9.7 and bias%=0.9 for the intra-day assay, and CV%=19.1 and bias%=-7.45 for the between-days assay. For precision, the range was CV%=1.8/11.6 in the intra-day and between-days assay, and for accuracy, the range was bias%=2.3/14.9 in the intra-day and between-days assay. In addition, the stability of piracetam in different conditions was verified. Piracetam proved to be stable in plasma during 4 weeks at -20 degrees C and for 36 h at 20 degrees C in the supernatant after protein precipitation. The new proposed method was used for a bioequivalence study of two medicines containing 800 mg piracetam.

  11. A fully validated LC-MS/MS method for simultaneous determination of nicotine and its metabolite cotinine in human serum and its application to a pharmacokinetic study after using nicotine transdermal delivery systems with standard heat application in adult smokers.

    Science.gov (United States)

    Abdallah, Inas A; Hammell, Dana C; Stinchcomb, Audra L; Hassan, Hazem E

    2016-05-01

    A sensitive and simple liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for simultaneous determination of nicotine and its main metabolite cotinine in human serum samples. Liquid-liquid extraction using ethyl acetate was employed for serum sample extractions. Chromatographic separation was achieved on Phenomenex Luna(®) HILIC column (150 mm x 3.0mm, 5 μm). Isocratic elution was performed using acetonitrile:100mM ammonium formate buffer (pH=3.2) (90:10, v/v) as the mobile phase, at a flow rate of 0.4 mL/min. Tandem mass spectrometric detection was employed at positive electrospray ionization in MRM mode for the determination of both nicotine and cotinine and their stable isotope labeled internal standards. Analysis was carried out in 8 min over a concentration range of 0.26-52.5 ng/mL and 7.0-1500 ng/mL for nicotine and cotinine, respectively. The assay was validated according to FDA guidelines for bioanalytical method validation and satisfactory results were obtained; the accuracy ranged between 93.39% and 105.73% for nicotine and between 93.04% and 107.26% for cotinine. No significant matrix effect was observed. Stability assays indicated both nicotine and cotinine were stable during sample storage, preparation and analytical procedures. The method was successfully applied to biological samples obtained from a pharmacokinetic study conducted in adult smokers to investigate heat effect on nicotine and cotinine serum levels after nicotine transdermal delivery system (TDS) application. Copyright © 2016 Elsevier B.V. All rights reserved.

  12. Methods to validate tooth-supporting regenerative therapies.

    Science.gov (United States)

    Padial-Molina, Miguel; Marchesan, Julie T; Taut, Andrei D; Jin, Qiming; Giannobile, William V; Rios, Hector F

    2012-01-01

    In humans, microbially induced inflammatory periodontal diseases are the primary initiators that disrupt the functional and structural integrity of the periodontium (i.e., the alveolar bone, the periodontal ligament, and the cementum). The reestablishment of its original structure, properties, and function constitutes a significant challenge in the development of new therapies to regenerate tooth-supporting defects. Preclinical models represent an important in vivo tool to critically evaluate and analyze the key aspects of novel regenerative therapies, including (1) safety, (2) effectiveness, (3) practicality, and (4) functional and structural stability over time. Therefore, these models provide foundational data that supports the clinical validation and the development of novel innovative regenerative periodontal technologies. Steps are provided on the use of the root fenestration animal model for the proper evaluation of periodontal outcome measures using the following parameters: descriptive histology, histomorphometry, immunostaining techniques, three-dimensional imaging, electron microscopy, gene expression analyses, and safety assessments. These methods will prepare investigators and assist them in identifying the key end points that can then be adapted to later stage human clinical trials.

  13. A method for the statistical interpretation of friction ridge skin impression evidence: Method development and validation.

    Science.gov (United States)

    Swofford, H J; Koertner, A J; Zemp, F; Ausdemore, M; Liu, A; Salyards, M J

    2018-04-03

    The forensic fingerprint community has faced increasing amounts of criticism by scientific and legal commentators, challenging the validity and reliability of fingerprint evidence due to the lack of an empirically demonstrable basis to evaluate and report the strength of the evidence in a given case. This paper presents a method, developed as a stand-alone software application, FRStat, which provides a statistical assessment of the strength of fingerprint evidence. The performance was evaluated using a variety of mated and non-mated datasets. The results show strong performance characteristics, often with values supporting specificity rates greater than 99%. This method provides fingerprint experts the capability to demonstrate the validity and reliability of fingerprint evidence in a given case and report the findings in a more transparent and standardized fashion with clearly defined criteria for conclusions and known error rate information thereby responding to concerns raised by the scientific and legal communities. Published by Elsevier B.V.

  14. Method validation for strobilurin fungicides in cereals and fruit

    DEFF Research Database (Denmark)

    Christensen, Hanne Bjerre; Granby, Kit

    2001-01-01

    ) and determination of the content by gas chromatography (GC) with electron capture (EC-), nitrogen/phosphorous (NP-), and mass spectrometric (MS-) detection. Three strobilurins, azoxystrobin, kresoxim-methyl and trifloxystrobin were validated on three matrices, wheat, apple and grapes. The validation was based...... and reproducibility were within the limits for repeatability and reproducibility given by the Horwitz equation. Validation was not accepted for azoxystrobin in grapes on all three detectors and for azoxystrobin in apple for the MS-detector. A comparison of matrix-matched standards versus standards in solvent showed...

  15. Green approaches in sample preparation of bioanalytical samples prior to chromatographic analysis.

    Science.gov (United States)

    Filippou, Olga; Bitas, Dimitrios; Samanidou, Victoria

    2017-02-01

    Sample preparation is considered to be the most challenging step of the analytical procedure, since it has an effect on the whole analytical methodology, therefore it contributes significantly to the greenness or lack of it of the entire process. The elimination of the sample treatment steps, pursuing at the same time the reduction of the amount of the sample, strong reductions in consumption of hazardous reagents and energy also maximizing safety for operators and environment, the avoidance of the use of big amount of organic solvents, form the basis for greening sample preparation and analytical methods. In the last decade, the development and utilization of greener and sustainable microextraction techniques is an alternative to classical sample preparation procedures. In this review, the main green microextraction techniques (solid phase microextraction, stir bar sorptive extraction, hollow-fiber liquid phase microextraction, dispersive liquid - liquid microextraction, etc.) will be presented, with special attention to bioanalytical applications of these environment-friendly sample preparation techniques which comply with the green analytical chemistry principles. Copyright © 2016 Elsevier B.V. All rights reserved.

  16. Fused Deposition Modeling 3D Printing for (Bio)analytical Device Fabrication: Procedures, Materials, and Applications.

    Science.gov (United States)

    Salentijn, Gert Ij; Oomen, Pieter E; Grajewski, Maciej; Verpoorte, Elisabeth

    2017-07-05

    In this work, the use of fused deposition modeling (FDM) in a (bio)analytical/lab-on-a-chip research laboratory is described. First, the specifications of this 3D printing method that are important for the fabrication of (micro)devices were characterized for a benchtop FDM 3D printer. These include resolution, surface roughness, leakage, transparency, material deformation, and the possibilities for integration of other materials. Next, the autofluorescence, solvent compatibility, and biocompatibility of 12 representative FDM materials were tested and evaluated. Finally, we demonstrate the feasibility of FDM in a number of important applications. In particular, we consider the fabrication of fluidic channels, masters for polymer replication, and tools for the production of paper microfluidic devices. This work thus provides a guideline for (i) the use of FDM technology by addressing its possibilities and current limitations, (ii) material selection for FDM, based on solvent compatibility and biocompatibility, and (iii) application of FDM technology to (bio)analytical research by demonstrating a broad range of illustrative examples.

  17. Alternative validation practice of an automated faulting measurement method.

    Science.gov (United States)

    2010-03-08

    A number of states have adopted profiler based systems to automatically measure faulting, : in jointed concrete pavements. However, little published work exists which documents the : validation process used for such automated faulting systems. This p...

  18. A mixed methods inquiry into the validity of data

    Directory of Open Access Journals (Sweden)

    Vaarst Mette

    2008-07-01

    Full Text Available Abstract Background Research in herd health management solely using a quantitative approach may present major challenges to the interpretation of the results, because the humans involved may have responded to their observations based on previous experiences and own beliefs. This challenge can be met through increased awareness and dialogue between researchers and farmers or other stakeholders about the background for data collection related to management and changes in management. By integrating quantitative and qualitative research methods in a mixed methods research approach, the researchers will improve their understanding of this potential bias of the observed data and farms, which will enable them to obtain more useful results of quantitative analyses. Case description An example is used to illustrate the potentials of combining quantitative and qualitative approaches to herd health related data analyses. The example is based on two studies on bovine metritis. The first study was a quantitative observational study of risk factors for metritis in Danish dairy cows based on data from the Danish Cattle Database. The other study was a semi-structured interview study involving 20 practicing veterinarians with the aim to gain insight into veterinarians' decision making when collecting and processing data related to metritis. Discussion and Evaluation The relations between risk factors and metritis in the first project supported the findings in several other quantitative observational studies; however, the herd incidence risk was highly skewed. There may be simple practical reasons for this, e.g. underreporting and differences in the veterinarians' decision making. Additionally, the interviews in the second project identified several problems with correctness and validity of data regarding the occurrence of metritis because of differences regarding case definitions and thresholds for treatments between veterinarians. Conclusion Studies where

  19. Validation of a horizontal method for trace elements in soil, sludge and biowaste

    OpenAIRE

    CRISTACHE CARMEN-ILEANA; COMERO Sara; LOCORO Giovanni; FISSIAUX ISABELLE; ALONSO RUIZ AGUSTIN; TANET GERARD; GAWLIK Bernd

    2013-01-01

    Validation of an analytical method is a necessary step in controlling the quality of quantitative analysis. Method validation is an established process, which is the provision of documentary evidence that a system fulfils its pre-defined specification or the process of providing that an analytical method is acceptable for its intended purpose. To implement a validated method for the analysis of 22000 soil samples stemming from 2009 LUCAS Soil Survey as well as from sewage sludge and treat...

  20. The method validation step of biological dosimetry accreditation process

    International Nuclear Information System (INIS)

    Roy, L.; Voisin, P.A.; Guillou, A.C.; Busset, A.; Gregoire, E.; Buard, V.; Delbos, M.; Voisin, Ph.

    2006-01-01

    One of the missions of the Laboratory of Biological Dosimetry (L.D.B.) of the Institute for Radiation and Nuclear Safety (I.R.S.N.) is to assess the radiological dose after an accidental overexposure suspicion to ionising radiation, by using radio-induced changes of some biological parameters. The 'gold standard' is the yield of dicentrics observed in patients lymphocytes, and this yield is converted in dose using dose effect relationships. This method is complementary to clinical and physical dosimetry, for medical team in charge of the patients. To obtain a formal recognition of its operational activity, the laboratory decided three years ago, to require an accreditation, by following the recommendations of both 17025 General Requirements for the Competence of Testing and Calibration Laboratories and 19238 Performance criteria for service laboratories performing biological dosimetry by cyto-genetics. Diagnostics, risks analysis were realized to control the whole analysis process leading to documents writing. Purchases, personnel department, vocational training were also included in the quality system. Audits were very helpful to improve the quality system. One specificity of this technique is that it is not normalized therefore apart from quality management aspects, several technical points needed some validations. An inventory of potentially influent factors was carried out. To estimate their real effect on the yield of dicentrics, a Placket-Burman experimental design was conducted. The effect of seven parameters was tested: the BUdr (bromodeoxyuridine), PHA (phytohemagglutinin) and colcemid concentration, the culture duration, the incubator temperature, the blood volume and the medium volume. The chosen values were calculated according to the uncertainties on the way they were measured i.e. pipettes, thermometers, test tubes. None of the factors has a significant impact on the yield of dicentrics. Therefore the uncertainty linked to their use was considered as

  1. Validation of pestice multi residue analysis method on cucumber

    International Nuclear Information System (INIS)

    2011-01-01

    In this study we aimed to validate the method of multi pesticide residue analysis on cucumber. Before real sample injection, system suitability test was performed in gas chromatography (GC). For this purpose, a sensitive pesticide mixture was used for GC-NPD and estimated the performance parameters such as number of effective theoretical plates, resolution factor, asymmetry, tailing and selectivity. It was detected that the system was suitable for calibration and sample injection. Samples were fortified at the level of 0.02, 0.2, 0.8 and 1 mg/kg with mixture of dichlorvos, malathion and chloropyrifos pesticides. In the fortification step 1 4C-carbaryl was also added on homogenized analytical portions to make use of 1 4C labelled pesticides for the determining extraction efficiency. Then the basic analytical process, such as ethyl acetate extraction, filtration, evaporation and cleanup, were performed. The GPC calibration using 1 4C- carbaryl and fortification mixture (dichlorvos, malathion and chloropyrifos) showed that pesticide fraction come through the column between the 8-23 ml fractions. The recovery of 1 4C-carbaryl after the extraction and cleanup step were 92.63-111.73 % and 74.83-102.22 %, respectively. The stability of pesticides during analysis is an important factor. In this study, stability test was performed including matrix effect. Our calculation and t test results showed that above mentioned pesticides were not stabile during sample processing in our laboratory conditions and it was found that sample comminution with dry ice may improve stability. In the other part of the study, 1 4C-chloropyrifos was used to determine homogeneity of analytical portions taken from laboratory samples. Use of 1 4C labelled pesticides allows us for quick quantification analyte, even with out clean-up. The analytical results show that after sample processing with waring blender, analytical portions were homogenous. Sample processing uncertainty depending on quantity of

  2. Empirical research methods for technology validation: Scaling up to practice

    NARCIS (Netherlands)

    Wieringa, Roelf J.

    tBefore technology is transferred to the market, it must be validated empirically by simulating future prac-tical use of the technology. Technology prototypes are first investigated in simplified contexts, and thesesimulations are scaled up to conditions of practice step by step as more becomes

  3. A validated RP-HPLC method for the determination of Irinotecan hydrochloride residues for cleaning validation in production area

    Directory of Open Access Journals (Sweden)

    Sunil Reddy

    2013-03-01

    Full Text Available Introduction: cleaning validation is an integral part of current good manufacturing practices in pharmaceutical industry. The main purpose of cleaning validation is to prove the effectiveness and consistency of cleaning in a given pharmaceutical production equipment to prevent cross contamination and adulteration of drug product with other active ingredient. Objective: a rapid, sensitive and specific reverse phase HPLC method was developed and validated for the quantitative determination of irinotecan hydrochloride in cleaning validation swab samples. Method: the method was validated using waters symmetry shield RP-18 (250mm x 4.6mm 5 µm column with isocratic mobile phase containing a mixture of 0.02 M potassium di-hydrogen ortho-phosphate, pH adjusted to 3.5 with ortho-phosphoric acid, methanol and acetonitrile (60:20:20 v/v/v. The flow rate of mobile phase was 1.0 mL/min with column temperature of 25°C and detection wavelength at 220nm. The sample injection volume was 100 µl. Results: the calibration curve was linear over a concentration range from 0.024 to 0.143 µg/mL with a correlation coefficient of 0.997. The intra-day and inter-day precision expressed as relative standard deviation were below 3.2%. The recoveries obtained from stainless steel, PCGI, epoxy, glass and decron cloth surfaces were more than 85% and there was no interference from the cotton swab. The detection limit (DL and quantitation limit (QL were 0.008 and 0.023 µg ml-1, respectively. Conclusion: the developed method was validated with respect to specificity, linearity, limit of detection and quantification, accuracy, precision and solution stability. The overall procedure can be used as part of a cleaning validation program in pharmaceutical manufacture of irinotecan hydrochloride.

  4. Validity in Mixed Methods Research in Education: The Application of Habermas' Critical Theory

    Science.gov (United States)

    Long, Haiying

    2017-01-01

    Mixed methods approach has developed into the third methodological movement in educational research. Validity in mixed methods research as an important issue, however, has not been examined as extensively as that of quantitative and qualitative research. Additionally, the previous discussions of validity in mixed methods research focus on research…

  5. pH adjustment of human blood plasma prior to bioanalytical sample preparation

    NARCIS (Netherlands)

    Hendriks, G.; Uges, D. R. A.; Franke, J. P.

    2008-01-01

    pH adjustment in bioanalytical sample preparation concerning ionisable compounds is one of the most common sample treatments. This is often done by mixing an aliquot of the sample with a proper buffer adjusted to the proposed pH. The pH of the resulting mixture however, does not necessarily have to

  6. Methods and validity of dietary assessments in four Scandinavian populations

    DEFF Research Database (Denmark)

    Bingham, S; Wiggins, H S; Englyst, H

    1982-01-01

    the survey, thereby implying that dietary habits had not changed as a result of the investigative technique. It is concluded that the dietary data are indicative of current patterns of food consumption and are sufficiently valid for comparison with data on cancer risk in the 4 areas.......Average intakes of nonstarch polysaccharides (dietary fiber), foods, and nutrients were measured in representative samples of 30 men aged 50-59 in 4 Scandinavian populations with a 3-4 fold difference in risk for large bowel cancer. The assessment technique, a 4-day weighed record of food consumed...

  7. Methods and validity of dietary assessments in four Scandinavian populations

    DEFF Research Database (Denmark)

    Bingham, S; Wiggins, H S; Englyst, H

    1982-01-01

    Average intakes of nonstarch polysaccharides (dietary fiber), foods, and nutrients were measured in representative samples of 30 men aged 50-59 in 4 Scandinavian populations with a 3-4 fold difference in risk for large bowel cancer. The assessment technique, a 4-day weighed record of food consumed...... the survey, thereby implying that dietary habits had not changed as a result of the investigative technique. It is concluded that the dietary data are indicative of current patterns of food consumption and are sufficiently valid for comparison with data on cancer risk in the 4 areas....

  8. Cross-validation method for bivariate measure with certain mixture

    Science.gov (United States)

    Sabre, Rachid

    2016-04-01

    We consider a pair of random variables (X, Y) whose probability measure is the sum of an absolutely continuous measure, a discrete measure and a finite number of absolutely continuous measures on several lines. An asymptotically unbiased and consistent estimate of the density of the continuous part is given in [13]. In this work, we focus on the choice of these parameters so that this estimate will be optimal and the rate of convergence will be better, we as well as its rate of convergence. To achieve this we use the cross-validation technics.

  9. Development and Validation of Analytical Method for Losartan ...

    African Journals Online (AJOL)

    HP

    Purpose: To develop a new spectrophotometric method for the analysis of losartan potassium in pharmaceutical formulations by making its complex with copper. Method: A coloured complex based on UV/Vis spectroscopic method was developed for the determination of losartan potassium concentration in pharmaceutical ...

  10. Method validation for preparing urine samples for downstream proteomic and metabolomic applications.

    OpenAIRE

    Ammerlaan, Wim; Trezzi, Jean-Pierre; Mathay, Conny; Hiller, Karsten; Betsou, Fay

    2014-01-01

    BACKGROUND: Formal validation of methods for biospecimen processing in the context of accreditation in laboratories and biobanks is lacking. A protocol for processing of a biospecimen (urine) was validated for fitness-for-purpose in terms of key downstream endpoints. METHODS: Urine processing was optimized for centrifugation conditions on the basis of microparticle counts at room temperature (RT) and at 4 degrees C. The optimal protocol was validated for performance (microparticle counts), an...

  11. Validation of techniques for the prediction of carboplatin exposure: application of Bayesian methods

    NARCIS (Netherlands)

    Huitema, A. D.; Mathôt, R. A.; Tibben, M. M.; Schellens, J. H.; Rodenhuis, S.; Beijnen, J. H.

    2000-01-01

    Several methods have been developed for the prediction of carboplatin exposure to facilitate pharmacokinetic guided dosing. The aim of this study was to develop and validate sparse data Bayesian methods for the estimation of carboplatin exposure and to validate other commonly applied techniques,

  12. Validation of a method for determination of amoxicillin residues applied to cleaning validation process in penicillins pharmaceutical industry

    OpenAIRE

    Gomes, Maria Luiza Pinheiro Costa; Souza, Scheilla Vitorino Carvalho de

    2010-01-01

    The aim of this work was the single-laboratory validation of a quantitative method for the determination of amoxicillin residues in support of cleaning control and validation. Linearity was demonstrated between 2.5 and 17.5 μg/mL, without matrix effects. Mean recoveries ranged from 84.00 to 103.74% and the relative standard deviation under repetitivity and within-reproducibility conditions were from 0.58 to 4.20% and from 0.79 to 4.39%, respectively. The theoretical limits of detection a...

  13. A VALIDATED STABILITY INDICATED RP-HPLC METHOD FOR DUTASTERIDE

    OpenAIRE

    D. Pavan Kumar a, b *, Naga Jhansi a, G. Srinivasa Rao b, Kirti Kumar Jain a

    2018-01-01

    ABSTRACT A Simple, Stability indicating, Isocratic, reverse phase High Performance Liquid Chromatographic (RPLC) related substance method was developed for Dutasteride in API. This method separates the impurities which are co-eluting in the pharmacopeia method. Successful separation of degradation impurities and synthetic impurities was achieved by YMC Triat phenyl column. Chromatographic was carried out on YMC Triat phenyl (150 X 4.6 mm, 3.0µm) column using 0.01M Potassium Dihydrogen Pho...

  14. Validation of two ribosomal RNA removal methods for microbial metatranscriptomics

    Energy Technology Data Exchange (ETDEWEB)

    He, Shaomei; Wurtzel, Omri; Singh, Kanwar; Froula, Jeff L; Yilmaz, Suzan; Tringe, Susannah G; Wang, Zhong; Chen, Feng; Lindquist, Erika A; Sorek, Rotem; Hugenholtz, Philip

    2010-10-01

    The predominance of rRNAs in the transcriptome is a major technical challenge in sequence-based analysis of cDNAs from microbial isolates and communities. Several approaches have been applied to deplete rRNAs from (meta)transcriptomes, but no systematic investigation of potential biases introduced by any of these approaches has been reported. Here we validated the effectiveness and fidelity of the two most commonly used approaches, subtractive hybridization and exonuclease digestion, as well as combinations of these treatments, on two synthetic five-microorganism metatranscriptomes using massively parallel sequencing. We found that the effectiveness of rRNA removal was a function of community composition and RNA integrity for these treatments. Subtractive hybridization alone introduced the least bias in relative transcript abundance, whereas exonuclease and in particular combined treatments greatly compromised mRNA abundance fidelity. Illumina sequencing itself also can compromise quantitative data analysis by introducing a G+C bias between runs.

  15. A method for enterprise architecture validation with colored Petri Nets

    Directory of Open Access Journals (Sweden)

    Mohammad Sadegh Alishahi

    2012-10-01

    Full Text Available Architecture includes so many documents where each describes one part of an enterprise. The problem in using such descriptions is on how to consider and use all components. Therefore, in order to organize the descriptions of enterprise architecture, we should use a framework. C4ISR is one of the enterprise architectural frameworks, which includes three views, contains some products. In order to show the products, this framework needs a unified notation, which covers all the products with various views. Unified Modeling Language (UML prepares such situation. But in order to decrease the expenses of enterprise architectural productions process, the architectural products shall be evaluated before the architectural implementation level happens. In this article, a simple way for validation of enterprise architectural products with Colored Petri Nets is presented to evaluate true behavior of architectural products well.

  16. APEX Airborne Imaging Spectrometer Uncertainty Budget and Vicarious Validation Method

    Science.gov (United States)

    Hueni, A.; Woolliams, E.; Schlaepfer, D.; Wulf, H.

    2017-12-01

    ESA's Airborne Imaging Spectrometer APEX (Airborne Prism Experiment) was developed by a Swiss-Belgian consortium and entered its operational phase at the end of 2010 (Schaepman et al. 2015). Work on the sensor model and on propagated uncertainties from the laboratory to the in-flight case has been carried out extensively within the framework of EMRP (European Metrology Research Program) as part of the Metrology for Earth Observation and Climate (MetEOC and MetEOC2). The uncertainty propagation has been implemented in the APEX Calibration Information System (Hueni et al. 2013) and the APEX Level 1 processor (Hueni et al. 2009), thus allowing the operational computation of uncertainties for any at-sensor radiance APEX imaging cube. This fosters a better understanding and aids evaluation of the results of vicarious validation using spectral ground control points stored in the spectral information system SPECCHIO (Hueni et al. 2016). The presented work ultimately benefits the production of traceable higher-level products and enables sensitivity analyses of models, e.g. 3D canopy simulations, parameterised by APEX radiances. Hueni, A., Biesemans, J., Meuleman, K., Dell'Endice, F., Schläpfer, D., et al (2009). "Structure, Components and Interfaces of the Airborne Prism Experiment (APEX) Processing and Archiving Facility." IEEE TGRS 47(1): 29-43. Hueni, A., Damm, A., Kneubuehler, M., Schläpfer, D. and Schaepman, M. (2016). "Field and Airborne Spectroscopy Cross-Validation - Some Considerations." IEEE JSTARS 10(3): 1117 - 1135. Hueni, A., Lenhard, K., Baumgartner, A. and Schaepman, M. (2013). "The APEX (Airborne Prism Experiment - Imaging Spectrometer) Calibration Information System." IEEE TGRS 51(11): 5169-5180. Schaepman, M., Jehle, M., Hueni, A., D'Odorico, P., Damm, A., et al (2015). "Advanced radiometry measurements and Earth science applications with the Airborne Prism Experiment (APEX)." Remote Sensing of Environment 158: 207-219.

  17. Validity of the Demirjian method for dental age estimation for ...

    African Journals Online (AJOL)

    2015-02-04

    Feb 4, 2015 ... French‑Canadian children; it has become the most widely used dental age examination method all over the world. Numerous studies have tested the applicability of this method in various population, including Australian,[6] Brazilian,[7]. British,[8,9] Caucasian American,[10] Chinese,[8,11] Dutch,[1]. Malay ...

  18. Medical documentation, bioanalytical evidence of an accidental human exposure to sulfur mustard and general therapy recommendations.

    Science.gov (United States)

    Steinritz, Dirk; Striepling, Enno; Rudolf, Klaus-Dieter; Schröder-Kraft, Claudia; Püschel, Klaus; Hullard-Pulstinger, Andreas; Koller, Marianne; Thiermann, Horst; Gandor, Felix; Gawlik, Michael; John, Harald

    2016-02-26

    Sulfur mustard (SM) is a chemical warfare agent (CWA) that was first used in World War I and in several military conflicts afterwards. The threat by SM is still present even today due to remaining stockpiles, old and abandoned remainders all over the world as well as to its ease of synthesis. CWA are banned by the Chemical Weapons Convention (CWC) interdicting their development, production, transport, stockpiling and use and are subjected to controlled destruction. The present case report describes an accidental exposure of three workers that occurred during the destruction of SM. All exposed workers presented a characteristic SM-related clinical picture that started about 4h after exposure with erythema and feeling of tension of the skin at the upper part of the body. Later on, superficial blister and a burning phenomenon of the affected skin areas developed. Similar symptoms occurred in all three patients differing severity. One patient presented sustained skin affections at the gluteal region while another patient came up with affections of the axilla and genital region. Fortunately, full recovery was observed on day 56 after exposure except some little pigmentation changes that were evident even on day 154 in two of the patients. SM-exposure was verified for all three patients using bioanalytical GC MS and LC MS/MS based methods applied to urine and plasma. Urinary biotransformation products of the β-lyase pathway were detected until 5 days after poisoning whereas albumin-SM adducts could be found until day 29 underlining the beneficial role of adduct detection for post-exposure verification. In addition, we provide general recommendations for management and therapy in case of SM poisoning. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  19. Critical role of bioanalytical strategies in investigation of clinical PK observations, a Phase I case study

    Science.gov (United States)

    Peng, Kun; Xu, Keyang; Liu, Luna; Hendricks, Robert; Delarosa, Reginald; Erickson, Rich; Budha, Nageshwar; Leabman, Maya; Song, An; Kaur, Surinder; Fischer, Saloumeh K

    2014-01-01

    RG7652 is a human immunoglobulin 1 (IgG1) monoclonal antibody (mAb) targeting proprotein convertase subtilisin/kexin type 9 (PCSK9) and is designed for the treatment of hypercholesterolemia. A target-binding enzyme-linked immunosorbent assay (ELISA) was developed to measure RG7652 levels in human serum in a Phase I study. Although target-binding assay formats are generally used to quantify free therapeutic, the actual therapeutic species being measured are affected by assay conditions, such as sample dilution and incubation time, and levels of soluble target in the samples. Therefore, in the presence of high concentrations of circulating target, the choice of reagents and assay conditions can have a significant effect on the observed pharmacokinetic (PK) profiles. Phase I RG7652 PK analysis using the ELISA data resulted in a nonlinear dose normalized exposure. An investigation was conducted to characterize the ELISA to determine whether the assay format and reagents may have contributed to the PK observation. In addition, to confirm the ELISA results, a second orthogonal method, liquid chromatography tandem mass spectrometry (LC-MS/MS) using a signature peptide as surrogate, was developed and implemented. A subset of PK samples, randomly selected from half of the subjects in the 6 single ascending dose (SAD) cohorts in the Phase I clinical study, was analyzed with the LC-MS/MS assay, and the data were found to be comparable to the ELISA data. This paper illustrates the importance of reagent characterization, as well as the benefits of using an orthogonal approach to eliminate bioanalytical contributions when encountering unexpected observations. PMID:25484037

  20. Validation of Alternative In Vitro Methods to Animal Testing: Concepts, Challenges, Processes and Tools.

    Science.gov (United States)

    Griesinger, Claudius; Desprez, Bertrand; Coecke, Sandra; Casey, Warren; Zuang, Valérie

    This chapter explores the concepts, processes, tools and challenges relating to the validation of alternative methods for toxicity and safety testing. In general terms, validation is the process of assessing the appropriateness and usefulness of a tool for its intended purpose. Validation is routinely used in various contexts in science, technology, the manufacturing and services sectors. It serves to assess the fitness-for-purpose of devices, systems, software up to entire methodologies. In the area of toxicity testing, validation plays an indispensable role: "alternative approaches" are increasingly replacing animal models as predictive tools and it needs to be demonstrated that these novel methods are fit for purpose. Alternative approaches include in vitro test methods, non-testing approaches such as predictive computer models up to entire testing and assessment strategies composed of method suites, data sources and decision-aiding tools. Data generated with alternative approaches are ultimately used for decision-making on public health and the protection of the environment. It is therefore essential that the underlying methods and methodologies are thoroughly characterised, assessed and transparently documented through validation studies involving impartial actors. Importantly, validation serves as a filter to ensure that only test methods able to produce data that help to address legislative requirements (e.g. EU's REACH legislation) are accepted as official testing tools and, owing to the globalisation of markets, recognised on international level (e.g. through inclusion in OECD test guidelines). Since validation creates a credible and transparent evidence base on test methods, it provides a quality stamp, supporting companies developing and marketing alternative methods and creating considerable business opportunities. Validation of alternative methods is conducted through scientific studies assessing two key hypotheses, reliability and relevance of the

  1. Validation of a laboratory method of measuring postpartum blood loss.

    Science.gov (United States)

    Chua, S; Ho, L M; Vanaja, K; Nordstrom, L; Roy, A C; Arulkumaran, S

    1998-01-01

    Laboratory methods give more accurate measurement of blood loss in the postpartum period than visual estimation. In order to evaluate a laboratory method used to quantify blood loss postpartum, blood lost at gynecological operations was collected in a measuring bottle. The measured amount of blood (50-1,000 ml) was then poured onto absorbent paper towels and sanitary pads, in order to mimic conditions when measuring blood loss in clinical trials in the postpartum period. The amount of blood absorbed onto the absorbent paper and sanitary pads was measured by a rapid method of automatic extraction and photometric measurement of alkaline hematin. The study shows that the method provides a reliable and accurate means of measuring blood loss. The error in each case was less than 10% with an intraclass correlation coefficient of almost 1.

  2. Validation of Standing Wave Liner Impedance Measurement Method, Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — Hersh Acoustical Engineering, Inc. proposes to establish the feasibility and practicality of using the Standing Wave Method (SWM) to measure the impedance of...

  3. Group 9 organometallic compounds for therapeutic and bioanalytical applications.

    Science.gov (United States)

    Ma, Dik-Lung; Chan, Daniel Shiu-Hin; Leung, Chung-Hang

    2014-12-16

    CONSPECTUS: Compared with organic small molecules, metal complexes offer several distinct advantages as therapeutic agents or biomolecular probes. Carbon atoms are typically limited to linear, trigonal planar, or tetrahedral geometries, with a maximum of two enantiomers being formed if four different substituents are attached to a single carbon. In contrast, an octahedral metal center with six different substituents can display up to 30 different stereoisomers. While platinum- and ruthenium-based anticancer agents have attracted significant attention in the realm of inorganic medicinal chemistry over the past few decades, group 9 complexes (i.e., iridium and rhodium) have garnered increased attention in therapeutic and bioanalytical applications due to their adjustable reactivity (from kinetically liable to substitutionally inert), high water solubility, stability to air and moisture, and relative ease of synthesis. In this Account, we describe our efforts in the development of group 9 organometallic compounds of general form [M(C(∧)N)2(N(∧)N)] (where M = Ir, Rh) as therapeutic agents against distinct biomolecular targets and as luminescent probes for the construction of oligonucleotide-based assays for a diverse range of analytes. Earlier studies by researchers had focused on organometallic iridium(III) and rhodium(III) half-sandwich complexes that show promising anticancer activity, although their precise mechanisms of action still remain unknown. More recently, kinetically-inert group 9 complexes have arisen as fascinating alternatives to organic small molecules for the specific targeting of enzyme activity. Research in our laboratory has shown that cyclometalated octahedral rhodium(III) complexes were active against Janus kinase 2 (JAK2) or NEDD8-activating enzyme (NAE) activity, or against NO production leading to antivasculogenic activity in cellulo. At the same time, recent interest in the development of small molecules as modulators of protein

  4. Flight critical system design guidelines and validation methods

    Science.gov (United States)

    Holt, H. M.; Lupton, A. O.; Holden, D. G.

    1984-01-01

    Efforts being expended at NASA-Langley to define a validation methodology, techniques for comparing advanced systems concepts, and design guidelines for characterizing fault tolerant digital avionics are described with an emphasis on the capabilities of AIRLAB, an environmentally controlled laboratory. AIRLAB has VAX 11/750 and 11/780 computers with an aggregate of 22 Mb memory and over 650 Mb storage, interconnected at 256 kbaud. An additional computer is programmed to emulate digital devices. Ongoing work is easily accessed at user stations by either chronological or key word indexing. The CARE III program aids in analyzing the capabilities of test systems to recover from faults. An additional code, the semi-Markov unreliability program (SURE) generates upper and lower reliability bounds. The AIRLAB facility is mainly dedicated to research on designs of digital flight-critical systems which must have acceptable reliability before incorporation into aircraft control systems. The digital systems would be too costly to submit to a full battery of flight tests and must be initially examined with the AIRLAB simulation capabilities.

  5. Risk calculators-methods, development, implementation, and validation.

    Science.gov (United States)

    Mansmann, Ulrich; Rieger, Anna; Strahwald, Brigitte; Crispin, Alexander

    2016-06-01

    A surgical risk calculator (SRC) estimates the probabilities of unfavorable outcomes such as complications or death after a specific surgery. The risk estimates are based on information regarding the patient's medical history and his current status. They are calculated using risk models derived from the analysis of data from a large number of previous patients in a similar clinical situation. This paper discusses several aspects of the SRC development and its implementation into clinical practice: the development of the statistical risk models, their validation and software implementation, the use of the SRC output for shared decision making in clinical settings, and the evaluation of the SRC's impact on individual patient outcomes as well as on the institution's quality of care of the clinical institution. Probably the most elaborate SRC is the ACS NSQIP SRC. A comparable project was started by the German Society for Visceral and General Surgery (DGAV) in the framework of its Study, Documentation, and Quality Center (StuDoQ). It is relevant to consider that the transportability of a SRC from a US American to a German setting is not straightforward. Risk calculators are important instruments for shared decision making between patients and doctor. Their implementation into clinical practice has to solve technical issues, and it is related to appropriate training of clinicians. There are specific study designs to evaluate the clinical impact of a SCR.

  6. Validation of ESR analyzer using Westergren ESR method.

    Science.gov (United States)

    Sikka, Meera; Tandon, Rajesh; Rusia, Usha; Madan, Nishi

    2007-07-01

    Erythrocyte sedimentation rate (ESR) is one of the most frequently ordered laboratory test. ESR analyzers were developed to provide a quick and efficient measure of ESR. We compared the results of ESR obtained by an ESR analyzer with those by the Westergren method in a group of 75 patients Linear regression analysis showed a good correlation between the two results (r = 0.818, p < 0.01). The intra class correlation was 0.82. The analyzer method had the advantages of safety, decreased technician time and improved patient care by providing quick results.

  7. Reliability and validity of the AutoCAD software method in lumbar lordosis measurement.

    Science.gov (United States)

    Letafatkar, Amir; Amirsasan, Ramin; Abdolvahabi, Zahra; Hadadnezhad, Malihe

    2011-12-01

    The aim of this study was to determine the reliability and validity of the AutoCAD software method in lumbar lordosis measurement. Fifty healthy volunteers with a mean age of 23 ± 1.80 years were enrolled. A lumbar lateral radiograph was taken on all participants, and the lordosis was measured according to the Cobb method. Afterward, the lumbar lordosis degree was measured via AutoCAD software and flexible ruler methods. The current study is accomplished in 2 parts: intratester and intertester evaluations of reliability as well as the validity of the flexible ruler and software methods. Based on the intraclass correlation coefficient, AutoCAD's reliability and validity in measuring lumbar lordosis were 0.984 and 0.962, respectively. AutoCAD showed to be a reliable and valid method to measure lordosis. It is suggested that this method may replace those that are costly and involve health risks, such as radiography, in evaluating lumbar lordosis.

  8. Reliability and Validity of the Research Methods Skills Assessment

    Science.gov (United States)

    Smith, Tamarah; Smith, Samantha

    2018-01-01

    The Research Methods Skills Assessment (RMSA) was created to measure psychology majors' statistics knowledge and skills. The American Psychological Association's Guidelines for the Undergraduate Major in Psychology (APA, 2007, 2013) served as a framework for development. Results from a Rasch analysis with data from n = 330 undergraduates showed…

  9. Validation, verification and comparison: Adopting new methods in ...

    African Journals Online (AJOL)

    2005-07-03

    Jul 3, 2005 ... A procedure for com- paring two presence/absence (P/A) methods was ... +44 1939 261084; e-mail: david.sartory@tesco.net. Received 1 November 2004; accepted in revised form 14 March .... Drinking Water Inspectorate (DWI) (DWI, 2000; Standing Com- mittee of Analysts, 2002), the statistical aspects of ...

  10. Development and validation of a spectroscopic method for the ...

    African Journals Online (AJOL)

    The assay results for the commercial formulation were within the limits specified in British Pharmacopoeia. Conclusion: Simultaneous quantification of miconazole (MCN) and hydrocortisone (HCA) by UV spectroscopy provides a simple, reliable and robust method for the characterization of a mixture of the drugs in a dosage ...

  11. Comparison of the performances and validation of three methods for ...

    African Journals Online (AJOL)

    SARAH

    2014-02-28

    Feb 28, 2014 ... they carry the bacteria in the oral cavity, notably on the tongue and the tonsils and in the lymph nodes, and they excrete them by their faeces [Thibodeau et al., 1999; Nesbakken et al. ., 2003].The Yersinia are psychotropic enterobacteria able to grow to low temperature and the method of enrichment to cold.

  12. Validity of common ultrasound methods of fetal weight estimation in ...

    African Journals Online (AJOL)

    Background: Accuracy of some ultrasound equations used in our locality for fetal weight estimation is doubtful. Objective: To assess the accuracy of common ultrasound equations used for fetal weight estimation. Subjects and Methods: A longitudinal study was conducted on selected Nigerian obstetric population at Central ...

  13. Obtaining Valid Response Rates: Considerations beyond the Tailored Design Method.

    Science.gov (United States)

    Huang, Judy Y.; Hubbard, Susan M.; Mulvey, Kevin P.

    2003-01-01

    Reports on the use of the tailored design method (TDM) to achieve high survey response in two separate studies of the dissemination of Treatment Improvement Protocols (TIPs). Findings from these two studies identify six factors may have influenced nonresponse, and show that use of TDM does not, in itself, guarantee a high response rate. (SLD)

  14. Validity of the Demirjian method for dental age estimation for ...

    African Journals Online (AJOL)

    2015-02-04

    Feb 4, 2015 ... Conclusions: It is appropriate to use the Demirjian method in southern Turkish children; however, a revision is needed in some ... Departments of Pediatric Dentistry and 1Orthodontics, Faculty of Dentistry, University of Akdeniz, Antalya, Turkey .... agenesis excluded from the study because dental anomalies.

  15. A method to determine validity and reliability of activity sensors

    NARCIS (Netherlands)

    Boerema, Simone Theresa; Hermens, Hermanus J.

    2013-01-01

    METHOD Four sensors were securely fastened to a mechanical oscillator (Vibration Exciter, type 4809, Brüel & Kjær) and moved at various frequencies (6.67Hz; 13.45Hz; 19.88Hz) within the range of human physical activity. For each of the three sensor axes, the sensors were simultaneously moved for

  16. Development and Validation of an HPLC Method for the ...

    African Journals Online (AJOL)

    A rapid, sensitive and selective reversed-phase high-performance liquid chromatographic (HPLC) method was developed for simultaneous determination of dextromethorphan hydrobromide (DXM), sodium benzoate (SB) and potassium guaiacolesulfonate (PGS) in cough mixture. The combined drug mixtures were ...

  17. Dentin Erosion: Method Validation and Efficacy of Fluoride Protection.

    Science.gov (United States)

    Carey, Clifton M; Brown, William

    2017-10-06

    The aging population experiences more gingival recession and root exposure which increases the opportunity for dentin erosion. This study tested the use of transverse microradiography (TMR) methods to assess dentin erosion and the interaction between fluoride and citric acid on the amount of erosion in the dentin samples. In a 4 × 3 interaction experimental design, four fluoride concentrations (0.00, 25.0, 50.0, and 100.0 mg/L) and three citric acid concentrations (0.0, 0.25, and 1.00%) were combined to form 12 experimental solutions. Forty-eight dentin samples were placed in the experimental solutions for 1 and 4 h and the amount of surface lost was determined by TMR methods. The resolution of the TMR method was 0.9 μm per pixel with a 0.1% and a 5% confidence interval of ±4.2 μm. Dentin erosion increased with the concentration of citric acid and time, the erosion decreased when concentration of fluoride was increased. Effects due to fluoride and citric acid concentrations individually, and their interaction on the amount of erosion observed was statistically significant (p < 0.0001). This study found that TMR methods are appropriate and that 25.0 mg/L was the optimal fluoride concentration to protect dentin from a 1.00% citric acid challenge.

  18. The Language Teaching Methods Scale: Reliability and Validity Studies

    Science.gov (United States)

    Okmen, Burcu; Kilic, Abdurrahman

    2016-01-01

    The aim of this research is to develop a scale to determine the language teaching methods used by English teachers. The research sample consisted of 300 English teachers who taught at Duzce University and in primary schools, secondary schools and high schools in the Provincial Management of National Education in the city of Duzce in 2013-2014…

  19. Human Factors methods concerning integrated validation of nuclear power plant control rooms

    International Nuclear Information System (INIS)

    Oskarsson, Per-Anders; Johansson, Bjoern J.E.; Gonzalez, Natalia

    2010-02-01

    The frame of reference for this work was existing recommendations and instructions from the NPP area, experiences from the review of the Turbic Validation and experiences from system validations performed at the Swedish Armed Forces, e.g. concerning military control rooms and fighter pilots. These enterprises are characterized by complex systems in extreme environments, often with high risks, where human error can lead to serious consequences. A focus group has been performed with representatives responsible for Human Factors issues from all Swedish NPP:s. The questions that were discussed were, among other things, for whom an integrated validation (IV) is performed and its purpose, what should be included in an IV, the comparison with baseline measures, the design process, the role of SSM, which methods of measurement should be used, and how the methods are affected of changes in the control room. The report brings different questions to discussion concerning the validation process. Supplementary methods of measurement for integrated validation are discussed, e.g. dynamic, psychophysiological, and qualitative methods for identification of problems. Supplementary methods for statistical analysis are presented. The study points out a number of deficiencies in the validation process, e.g. the need of common guidelines for validation and design, criteria for different types of measurements, clarification of the role of SSM, and recommendations for the responsibility of external participants in the validation process. The authors propose 12 measures for taking care of the identified problems

  20. Impurities in biogas - validation of analytical methods for siloxanes; Foeroreningar i biogas - validering av analysmetodik foer siloxaner

    Energy Technology Data Exchange (ETDEWEB)

    Arrhenius, Karine; Magnusson, Bertil; Sahlin, Eskil [SP Technical Research Institute of Sweden, Boraas (Sweden)

    2011-11-15

    Biogas produced from digester or landfill contains impurities which can be harmful for component that will be in contact with the biogas during its utilization. Among these, the siloxanes are often mentioned. During combustion, siloxanes are converted to silicon dioxide which accumulates on the heated surfaces in combustion equipment. Silicon dioxide is a solid compound and will remain in the engine and cause damages. Consequently, it is necessary to develop methods for the accurate determination of these compounds in biogases. In the first part of this report, a method for analysis of siloxanes in biogases was validated. The sampling was performed directly at the plant by drawing a small volume of biogas onto an adsorbent tube under a short period of time. These tubes were subsequently sent to the laboratory for analysis. The purpose of method validation is to demonstrate that the established method is fit for the purpose. This means that the method, as used by the laboratory generating the data, will provide data that meets a set of criteria concerning precision and accuracy. At the end, the uncertainty of the method was calculated. In the second part of this report, the validated method was applied to real samples collected in waste water treatment plants, co-digestion plants and plants digesting other wastes (agriculture waste). Results are presented at the end of this report. As expected, the biogases from waste water treatment plants contained largely higher concentrations of siloxanes than biogases from co-digestion plants and plants digesting agriculture wastes. The concentration of siloxanes in upgraded biogas regardless of which feedstock was digested and which upgrading technique was used was low.

  1. A mixed methods inquiry into the validity of data

    DEFF Research Database (Denmark)

    Kristensen, Erling Lundager; Nielsen, Dorthe B; Jensen, Laila N

    2008-01-01

    increased awareness and dialogue between researchers and farmers or other stakeholders about the background for data collection related to management and changes in management. By integrating quantitative and qualitative research methods in a mixed methods research approach, the researchers will improve....... The example is based on two studies on bovine metritis. The first study was a quantitative observational study of risk factors for metritis in Danish dairy cows based on data from the Danish Cattle Database. The other study was a semi-structured interview study involving 20 practicing veterinarians...... with the aim to gain insight into veterinarians' decision making when collecting and processing data related to metritis. Discussion and Evaluation The relations between risk factors and metritis in the first project supported the findings in several other quantitative observational studies; however, the herd...

  2. A Virtual Upgrade Validation Method for Software-Reliant Systems

    Science.gov (United States)

    2012-06-01

    TR-005 [Clements 2001] Clements, Paul , Kazman, Rick, & Klein, Mark. Evaluating Software Architectures: Methods and Case Studies. Addison-Wesley...Technologies (RTS2009)—Ada Europe. Brest , France, June 2009. Lecture Notes in Computer Science 5570, Springer, 2009. http://julien.gunnm.org/data/publications...on Reliable Software Technologies - Ada- Europe’2009 (Ada-Europe 2009). Brest , France, June 2009. ACM, 2009. [Thiele 2000] Thiele, L., Chakraborty

  3. THE EXPERIMENTAL VALIDATION OF THE GROUNDING DEVICE RESISTANCE MEASUREMENT METHOD

    Directory of Open Access Journals (Sweden)

    I. V. Nizhevskyi

    2016-12-01

    Full Text Available Purpose. The paper considers experimental research of three-electrode units for measuring the resistance of grounding devices for different purposes. Methodology. The experimental study of the method of resistance measurement of grounding devices for any design in any soil structure using the method of physical modeling is presented. Results. By results of model operation the set of equations of the sixth order is solved. It allowed to determine the own and mutual impedance in the three-electrode unit with high accuracy without searching the point of zero potential. Features of measuring and defining the own and relative resistances of various combinations of electrodes for three-electrode measuring unit are considered. Originality. The necessity of finding a zero potential point is excluded. Practical value. The proposed method provides the smallest possible spacing of potential electrodes outside the grounding devices. This reduces the wiring length measurement circuit in several times, increases the ratio «signal – noise», removes the restrictions on building of the territory outside the test grounding device.

  4. The development and validation of control rod calculation methods

    International Nuclear Information System (INIS)

    Rowlands, J.L.; Sweet, D.W.; Franklin, B.M.

    1979-01-01

    Fission rate distributions have been measured in the zero power critical facility, ZEBRA, for a series of eight different arrays of boron carbide control rods. Diffusion theory calculations have been compared with these measurements. The normalised fission rates differ by up to about 30% in some regions, between the different arrays, and these differences are well predicted by the calculations. A development has been made to a method used to produce homogenised cross sections for lattice regions containing control rods. Calculations show that the method also reproduces the reaction rate within the rod and the fission rate dip at the surface of the rod in satisfactory agreement with the more accurate calculations which represent the fine structure of the rod. A comparison between diffusion theory and transport theory calculations of control rod reactivity worths in the CDFR shows that for the standard design method the finite mesh approximation and the difference between diffusion theory and transport theory (the transport correction) tend to cancel and result in corrections to be applied to the standard mesh diffusion theory calculations of about +- 2% or less. This result applies for mesh centred finite difference diffusion theory codes and for the arrays of natural boron carbide control rods for which the calculations were made. Improvements have also been made to the effective diffusion coefficients used in diffusion theory calculations for control rod followers and these give satisfactory agreement with transport theory calculations. (U.K.)

  5. Use of multiple cluster analysis methods to explore the validity of a community outcomes concept map.

    Science.gov (United States)

    Orsi, Rebecca

    2017-02-01

    Concept mapping is now a commonly-used technique for articulating and evaluating programmatic outcomes. However, research regarding validity of knowledge and outcomes produced with concept mapping is sparse. The current study describes quantitative validity analyses using a concept mapping dataset. We sought to increase the validity of concept mapping evaluation results by running multiple cluster analysis methods and then using several metrics to choose from among solutions. We present four different clustering methods based on analyses using the R statistical software package: partitioning around medoids (PAM), fuzzy analysis (FANNY), agglomerative nesting (AGNES) and divisive analysis (DIANA). We then used the Dunn and Davies-Bouldin indices to assist in choosing a valid cluster solution for a concept mapping outcomes evaluation. We conclude that the validity of the outcomes map is high, based on the analyses described. Finally, we discuss areas for further concept mapping methods research. Copyright © 2016 Elsevier Ltd. All rights reserved.

  6. Rationale and methods of the European Food Consumption Validation (EFCOVAL) Project

    NARCIS (Netherlands)

    Boer, de E.J.; Slimani, N.; Boeing, H.; Feinberg, M.; Leclerq, C.; Trolle, E.; Amiano, P.; Andersen, L.F.; Freisling, H.; Geelen, A.; Harttig, U.; Huybrechts, I.; Kaic-Rak, A.; Lafay, L.; Lillegaard, I.T.L.; Ruprich, J.; Vries, de J.H.M.; Ocke, M.C.

    2011-01-01

    Background/Objectives: The overall objective of the European Food Consumption Validation (EFCOVAL) Project was to further develop and validate a trans-European food consumption method to be used for the evaluation of the intake of foods, nutrients and potentially hazardous chemicals within the

  7. Applying the Mixed Methods Instrument Development and Construct Validation Process: the Transformative Experience Questionnaire

    Science.gov (United States)

    Koskey, Kristin L. K.; Sondergeld, Toni A.; Stewart, Victoria C.; Pugh, Kevin J.

    2018-01-01

    Onwuegbuzie and colleagues proposed the Instrument Development and Construct Validation (IDCV) process as a mixed methods framework for creating and validating measures. Examples applying IDCV are lacking. We provide an illustrative case integrating the Rasch model and cognitive interviews applied to the development of the Transformative…

  8. Validity of a digital diet estimation method for use with preschool children

    Science.gov (United States)

    The validity of using the Remote Food Photography Method (RFPM) for measuring food intake of minority preschool children's intake is not well documented. The aim of the study was to determine the validity of intake estimations made by human raters using the RFPM compared with those obtained by weigh...

  9. VALIDATION OF THE ASSR TEST THROUGH COMPLEMENTARY AUDIOLOGYICAL METHODS

    Directory of Open Access Journals (Sweden)

    C. Mârtu

    2016-04-01

    Full Text Available Introduction: Auditory Steady State Response (ASSR is an objective method for determining the auditive threshold, applicable and necessary especially in children. The test is extremely important for recommending cochlear implant in children. The aim of the study was to compare pure tone audiometry responses and auditory steady-state thresholds. Materials and method: The study was performed on a group including both patients with normal hearing and with hearing loss. The main inclusion criteria accepted only patients with normal otomicroscopic aspect, normal tympanogram, capable to respond to pure tone audiometry, and with ear conduction thresholds between 0 and 80 dB NHL. The patients with suppurative otic processes or ear malformations were excluded. The research protocol was followed, the tests being performed in soundproofed rooms, starting with pure tone audiometry followed, after a pause, by ASSR determinations at frequencies of 0.5, 1.2 and 4 KHz. The audiological instruments were provided by a single manufacturer. ASSR was recorded at least two times for both borderline intensities, namely the one defining the auditory threshold and the first no-response intensity. The recorded responses were stored in a database and further processed in Excel. Discussion: The differences observed between pure tone audiometry and ASSR thresholds are important at 500 Hz and insignificant at the other frequencies. When approaching the PTA-ASSR relation, whatever the main characteristic between the PTA and ASSR thresholds in one ear, the profile of the lines gap maintains the same shape on the opposite ear. Conclusions: ASSR is a confident objective test, maintaining attention to low frequencies, where some differences might occur.

  10. Content validity across methods of malnutrition assessment in patients with cancer is limited.

    Science.gov (United States)

    Sealy, Martine J; Nijholt, Willemke; Stuiver, Martijn M; van der Berg, Marit M; Roodenburg, Jan L N; van der Schans, Cees P; Ottery, Faith D; Jager-Wittenaar, Harriët

    2016-08-01

    To identify malnutrition assessment methods in cancer patients and assess their content validity based on internationally accepted definitions for malnutrition. Systematic review of studies in cancer patients that operationalized malnutrition as a variable, published since 1998. Eleven key concepts, within the three domains reflected by the malnutrition definitions acknowledged by European Society for Clinical Nutrition and Metabolism (ESPEN) and the American Society for Parenteral and Enteral Nutrition (ASPEN): A: nutrient balance; B: changes in body shape, body area and body composition; and C: function, were used to classify content validity of methods to assess malnutrition. Content validity indices (M-CVIA-C) were calculated per assessment method. Acceptable content validity was defined as M-CVIA-C ≥ 0.80. Thirty-seven assessment methods were identified in the 160 included articles. Mini Nutritional Assessment (M-CVIA-C = 0.72), Scored Patient-Generated Subjective Global Assessment (M-CVIA-C = 0.61), and Subjective Global Assessment (M-CVIA-C = 0.53) scored highest M-CVIA-C. A large number of malnutrition assessment methods are used in cancer research. Content validity of these methods varies widely. None of these assessment methods has acceptable content validity, when compared against a construct based on ESPEN and ASPEN definitions of malnutrition. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Validation of wind speed prediction methods at offshore sites

    Science.gov (United States)

    McQueen, Dougal; Watson, Simon

    2006-01-01

    As ever more offshore sites are being investigated for the installation of wind farms, there is a need for accurate estimates of the long-term mean wind speeds at these sites. The cost of installing masts at offshore sites is high compared with onshore sites. In the short term this cost may be difficult to avoid. However, if a developer could get an estimate of the expected long-term mean wind speed at a potential offshore site using available onshore data sets, this could at least inform the choice of site for more advanced monitoring. With this in mind we present the results of using a number of simple standard analyses to infer the wind speed at three UK offshore masts and a mast and lighthouse off the coast of Ireland. Onshore surface wind measurements, upper air measurements, numerical weather prediction model output pressure data on a regular grid, wind speed output from two numerical weather prediction models and reanalysis data are transformed to the sites of interest using relatively simple methods neglecting the effect of topography or a roughness change-induced internal boundary layer and assuming neutral atmospheric stability. The predicted wind speeds are compared with actual measurements at the offshore masts and any discrepancies are assessed and discussed. Copyright

  12. An Engineering Method of Civil Jet Requirements Validation Based on Requirements Project Principle

    Science.gov (United States)

    Wang, Yue; Gao, Dan; Mao, Xuming

    2018-03-01

    A method of requirements validation is developed and defined to meet the needs of civil jet requirements validation in product development. Based on requirements project principle, this method will not affect the conventional design elements, and can effectively connect the requirements with design. It realizes the modern civil jet development concept, which is “requirement is the origin, design is the basis”. So far, the method has been successfully applied in civil jet aircraft development in China. Taking takeoff field length as an example, the validation process and the validation method of the requirements are detailed introduced in the study, with the hope of providing the experiences to other civil jet product design.

  13. Content validity across methods of malnutrition assessment in patients with cancer is limited

    NARCIS (Netherlands)

    Sealy, Martine J.; Nijholt, Willemke; Stuiver, Martijn M.; van der Berg, Marit M.; Roodenburg, Jan L. N.; Schans, van der Cees P.; Ottery, Faith D.; Jager-Wittenaar, Harriet

    Objective: To identify malnutrition assessment methods in cancer patients and assess their content validity based on internationally accepted definitions for malnutrition. Study Design and Setting: Systematic review of studies in cancer patients that operationalized malnutrition as a variable,

  14. Relationship of Ambient Atmosphere and Biological Aerosol Responses from a Fielded Pyrolysis-Gas Chromatography-Ion Mobility Spectrometry Bioanalytical Detector

    National Research Council Canada - National Science Library

    Snyder, A

    2003-01-01

    .... A pyrolysis-gas chromatography-ion mobility spectrometry stand-alone bioaerosol system was interfaced to an aerosol concentrator to collect ambient background aerosols and produce bioanalytical...

  15. VALIDATED SPECTROPHOTMETRIC METHOD FOR THE DETERMINATION OF SALBUTAMOL SULPHATE IN BULK AND PHARMACEUTICAL DOSAGE FORMS

    OpenAIRE

    Eswarudu.M.M; Sushma.M; Sushmitha.M; Yamini.K

    2012-01-01

    A new, simple, accurate and sensitive spectrophotometric method has been developed for the estimation of Salbutamol sulphate in bulk and in pharmaceutical formulations. Salbutamol sulphate shows ʎ max at 292 nm. The drug follows the beer’s lambert’s law in the concentration range of 20-100µ ml. the method was validated by following the analytical performance parameters as suggested by the international conference on harmonization which included accuracy, precision, linearity. All validation p...

  16. Comparing the Validity of Non-Invasive Methods in Measuring Thoracic Kyphosis and Lumbar Lordosis

    Directory of Open Access Journals (Sweden)

    Mohammad Yousefi

    2012-04-01

    Full Text Available Background: the purpose of this article is to study the validity of each of the non-invasive methods (flexible ruler, spinal mouse, and processing the image versus the one through-Ray radiation (the basic method and comparing them with each other.Materials and Methods: for evaluating the validity of each of these non-invasive methods, the thoracic Kyphosis and lumber Lordosis angle of 20 students of Birjand University (age mean and standard deviation: 26±2, weight: 72±2.5 kg, height: 169±5.5 cm through fours methods of flexible ruler, spinal mouse, and image processing and X-ray.Results: the results indicated that the validity of the methods including flexible ruler, spinal mouse, and image processing in measuring the thoracic Kyphosis and lumber Lordosis angle respectively have an adherence of 0.81, 0.87, 0.73, 0.76, 0.83, 0.89 (p>0.05. As a result, regarding the gained validity against the golden method of X-ray, it could be stated that the three mentioned non-invasive methods have adequate validity. In addition, the one-way analysis of variance test indicated that there existed a meaningful relationship between the three methods of measuring the thoracic Kyphosis and lumber Lordosis, and with respect to the Tukey’s test result, the image processing method is the most precise one.Conclusion as a result, this method could be used along with other non-invasive methods as a valid measuring method.

  17. Two Validated HPLC Methods for the Quantification of Alizarin and other Anthraquinones in Rubia tinctorum Cultivars

    NARCIS (Netherlands)

    Derksen, G.C.H.; Lelyveld, G.P.; Beek, van T.A.; Capelle, A.; Groot, de Æ.

    2004-01-01

    Direct and indirect HPLC-UV methods for the quantitative determination of anthraquinones in dried madder root have been developed, validated and compared. In the direct method, madder root was extracted twice with refluxing ethanol-water. This method allowed the determination of the two major native

  18. Validation of laboratory-scale recycling test method of paper PSA label products

    Science.gov (United States)

    Carl Houtman; Karen Scallon; Richard Oldack

    2008-01-01

    Starting with test methods and a specification developed by the U.S. Postal Service (USPS) Environmentally Benign Pressure Sensitive Adhesive Postage Stamp Program, a laboratory-scale test method and a specification were developed and validated for pressure-sensitive adhesive labels, By comparing results from this new test method and pilot-scale tests, which have been...

  19. Validation of the interface-GMRES(R) solution method for fluid-structure interactions

    NARCIS (Netherlands)

    Michler, C.; Van Brummelen, E.H.; In 't Groen, R.; De Borst, R.

    2006-01-01

    The numerical solution of fluid-structure interactions with the customary subiteration method incurs numerous deficiencies. We validate a recently proposed solution method based on the conjugation of subiteration with a Newton-Krylov method, and demonstrate its superiority and beneficial

  20. Validation and comparison of methods for enumeration of faecal coliforms and Escherichia coli in bivalve molluscs

    NARCIS (Netherlands)

    Mooijman KA; Poelman M; Stegeman H; Warmerdam C; Teunis PFM; Roda Husman AM de; RIKILT; MGB

    2007-01-01

    The main result of the validation study to show the equivalence of two methods for the enumeration of faecal coliforms in bivalve molluscs is that the plate count method on Mac Conkey agar was indeed found to be equivalent to the MPN method. Meaning that the Netherlands fulfilled the demands as

  1. Development and Validation of a New RP-HPLC Method for the ...

    African Journals Online (AJOL)

    Development and Validation of a New RP-HPLC Method for the Determination of Aprepitant in Solid Dosage Forms. ... Tropical Journal of Pharmaceutical Research ... Methods: The method developed for the determination of APT in capsule formulation involved using RP-HPLC which incorporated a C18 column 250 x 2.5 ...

  2. A long-term validation of the modernised DC-ARC-OES solid-sample method

    Energy Technology Data Exchange (ETDEWEB)

    Florian, K. [Dept. of Chemistry, Technical University of Kosice (Slovakia); Hassler, J.; Foerster, O. [Elektroschmelzwerk GmbH, Kempten (Germany)

    2001-12-01

    The validation procedure based on ISO 17 025 standard has been used to study and illustrate both the long-term stability of the calibration process of the DC-ARC solid sample spectrometric method and the main validation criteria of the method. In the calculation of the validation characteristics depending on the linearity(calibration), also the fulfilment of predetermining criteria such as normality and homoscedasticity was checked. In order to decide whether there are any trends in the time-variation of the analytical signal or not, also the Neumann test of trend was applied and evaluated. Finally, a comparison with similar validation data of the ETV-ICP-OES method was carried out. (orig.)

  3. Fuzzy-logic based strategy for validation of multiplex methods: example with qualitative GMO assays.

    Science.gov (United States)

    Bellocchi, Gianni; Bertholet, Vincent; Hamels, Sandrine; Moens, W; Remacle, José; Van den Eede, Guy

    2010-02-01

    This paper illustrates the advantages that a fuzzy-based aggregation method could bring into the validation of a multiplex method for GMO detection (DualChip GMO kit, Eppendorf). Guidelines for validation of chemical, bio-chemical, pharmaceutical and genetic methods have been developed and ad hoc validation statistics are available and routinely used, for in-house and inter-laboratory testing, and decision-making. Fuzzy logic allows summarising the information obtained by independent validation statistics into one synthetic indicator of overall method performance. The microarray technology, introduced for simultaneous identification of multiple GMOs, poses specific validation issues (patterns of performance for a variety of GMOs at different concentrations). A fuzzy-based indicator for overall evaluation is illustrated in this paper, and applied to validation data for different genetically modified elements. Remarks were drawn on the analytical results. The fuzzy-logic based rules were shown to be applicable to improve interpretation of results and facilitate overall evaluation of the multiplex method.

  4. Method development and validation of potent pyrimidine derivative by UV-VIS spectrophotometer.

    Science.gov (United States)

    Chaudhary, Anshu; Singh, Anoop; Verma, Prabhakar Kumar

    2014-12-01

    A rapid and sensitive ultraviolet-visible (UV-VIS) spectroscopic method was developed for the estimation of pyrimidine derivative 6-Bromo-3-(6-(2,6-dichlorophenyl)-2-(morpolinomethylamino) pyrimidine4-yl) -2H-chromen-2-one (BT10M) in bulk form. Pyrimidine derivative was monitored at 275 nm with UV detection, and there is no interference of diluents at 275 nm. The method was found to be linear in the range of 50 to 150 μg/ml. The accuracy and precision were determined and validated statistically. The method was validated as a guideline. The results showed that the proposed method is suitable for the accurate, precise, and rapid determination of pyrimidine derivative. Graphical Abstract Method development and validation of potent pyrimidine derivative by UV spectroscopy.

  5. Session-RPE Method for Training Load Monitoring: Validity, Ecological Usefulness, and Influencing Factors

    Directory of Open Access Journals (Sweden)

    Monoem Haddad

    2017-11-01

    Full Text Available Purpose: The aim of this review is to (1 retrieve all data validating the Session-rating of perceived exertion (RPE-method using various criteria, (2 highlight the rationale of this method and its ecological usefulness, and (3 describe factors that can alter RPE and users of this method should take into consideration.Method: Search engines such as SPORTDiscus, PubMed, and Google Scholar databases in the English language between 2001 and 2016 were consulted for the validity and usefulness of the session-RPE method. Studies were considered for further analysis when they used the session-RPE method proposed by Foster et al. in 2001. Participants were athletes of any gender, age, or level of competition. Studies using languages other than English were excluded in the analysis of the validity and reliability of the session-RPE method. Other studies were examined to explain the rationale of the session-RPE method and the origin of RPE.Results: A total of 950 studies cited the Foster et al. study that proposed the session RPE-method. 36 studies have examined the validity and reliability of this proposed method using the modified CR-10.Conclusion: These studies confirmed the validity and good reliability and internal consistency of session-RPE method in several sports and physical activities with men and women of different age categories (children, adolescents, and adults among various expertise levels. This method could be used as “standing alone” method for training load (TL monitoring purposes though some recommend to combine it with other physiological parameters as heart rate.

  6. Development and validation of an UHPLC-ESI-QTOF-MS method for quantification of the highly hydrophilic amyloid-β oligomer eliminating all-D-enantiomeric peptide RD2 in mouse plasma.

    Science.gov (United States)

    Hupert, Michelle; Elfgen, Anne; Schartmann, Elena; Schemmert, Sarah; Buscher, Brigitte; Kutzsche, Janine; Willbold, Dieter; Santiago-Schübel, Beatrix

    2018-01-15

    During preclinical drug development, a method for quantification of unlabeled compounds in blood plasma samples from treatment or pharmacokinetic studies in mice is required. In the current work, a rapid, specific, sensitive and validated liquid chromatography mass-spectrometric UHPLC-ESI-QTOF-MS method was developed for the quantification of the therapeutic compound RD2 in mouse plasma. RD2 is an all-D-enantiomeric peptide developed for the treatment of Alzheimer's disease, a progressive neurodegenerative disease finally leading to dementia. Due to RD2's highly hydrophilic properties, the sample preparation and the chromatographic separation and quantification were very challenging. The chromatographic separation of RD2 and its internal standard were accomplished on an Acquity UPLC BEH C18 column (2.1 × 100 mm, 1.7 μm particle size) within 6.5 min at 50 °C with a flow rate of 0.5 mL/min. Mobile phases consisted of water and acetonitrile with 1% formic acid and 0.025% heptafluorobutyric acid, respectively. Ions were generated by electrospray ionization (ESI) in the positive mode and the peptide was quantified by QTOF-MS. The developed extraction method for RD2 from mouse plasma revealed complete recovery. The linearity of the calibration curve was in the range of 5.3 ng/mL to 265 ng/mL (r 2  > 0.999) with a lower limit of detection (LLOD) of 2.65 ng/mL and a lower limit of quantification (LLOQ) of 5.3 ng/mL. The intra-day and inter-day accuracy and precision of RD2 in plasma ranged from -0.54% to 2.21% and from 1.97% to 8.18%, respectively. Moreover, no matrix effects were observed and RD2 remained stable in extracted mouse plasma at different conditions. Using this validated bioanalytical method, plasma samples of unlabeled RD2 or placebo treated mice were analyzed. The herein developed UHPLC-ESI-QTOF-MS method is a suitable tool for the quantitative analysis of unlabeled RD2 in plasma samples of treated mice. Copyright © 2017

  7. Validation of innovative technologies and strategies for regulatory safety assessment methods: challenges and opportunities.

    Science.gov (United States)

    Stokes, William S; Wind, Marilyn

    2010-01-01

    Advances in science and innovative technologies are providing new opportunities to develop test methods and strategies that may improve safety assessments and reduce animal use for safety testing. These include high throughput screening and other approaches that can rapidly measure or predict various molecular, genetic, and cellular perturbations caused by test substances. Integrated testing and decision strategies that consider multiple types of information and data are also being developed. Prior to their use for regulatory decision-making, new methods and strategies must undergo appropriate validation studies to determine the extent that their use can provide equivalent or improved protection compared to existing methods and to determine the extent that reproducible results can be obtained in different laboratories. Comprehensive and optimal validation study designs are expected to expedite the validation and regulatory acceptance of new test methods and strategies that will support improved safety assessments and reduced animal use for regulatory testing.

  8. Development and validation of a dissolution method using HPLC for diclofenac potassium in oral suspension

    Directory of Open Access Journals (Sweden)

    Alexandre Machado Rubim

    2014-04-01

    Full Text Available The present study describes the development and validation of an in vitro dissolution method for evaluation to release diclofenac potassium in oral suspension. The dissolution test was developed and validated according to international guidelines. Parameters like linearity, specificity, precision and accuracy were evaluated, as well as the influence of rotation speed and surfactant concentration on the medium. After selecting the best conditions, the method was validated using apparatus 2 (paddle, 50-rpm rotation speed, 900 mL of water with 0.3% sodium lauryl sulfate (SLS as dissolution medium at 37.0 ± 0.5°C. Samples were analyzed using the HPLC-UV (PDA method. The results obtained were satisfactory for the parameters evaluated. The method developed may be useful in routine quality control for pharmaceutical industries that produce oral suspensions containing diclofenac potassium.

  9. VALIDATION HPLC METHOD FOR THE DETERMINATION OF CLONIDINE HYDROCHLORIDE RESIDUES FROM PHARMACEUTICAL MANUFACTURING EQUIPMENT

    Directory of Open Access Journals (Sweden)

    A. V. Yegorova

    2015-04-01

    Full Text Available Highly sensitive HPLC method of determination of clonidine hydrochloride trace amounts for validation cleaning process of the pharmaceutical equipment has been proposed. The developed method has been validated on the following parameters: specificity, linearity, precision, limit of detection and limit of quantification. The calibration curve was linear over the concentration range of 0.1-6.0 mg / ml, the limit of detection is 0.026 μg/ml. It has been found that clonidine hydrochloride solutions are stable for 48 hours. Effectiveness of the method of sampling is more than 95%.

  10. Increased efficacy for in-house validation of real-time PCR GMO detection methods.

    Science.gov (United States)

    Scholtens, I M J; Kok, E J; Hougs, L; Molenaar, B; Thissen, J T N M; van der Voet, H

    2010-03-01

    To improve the efficacy of the in-house validation of GMO detection methods (DNA isolation and real-time PCR, polymerase chain reaction), a study was performed to gain insight in the contribution of the different steps of the GMO detection method to the repeatability and in-house reproducibility. In the present study, 19 methods for (GM) soy, maize canola and potato were validated in-house of which 14 on the basis of an 8-day validation scheme using eight different samples and five on the basis of a more concise validation protocol. In this way, data was obtained with respect to the detection limit, accuracy and precision. Also, decision limits were calculated for declaring non-conformance (>0.9%) with 95% reliability. In order to estimate the contribution of the different steps in the GMO analysis to the total variation variance components were estimated using REML (residual maximum likelihood method). From these components, relative standard deviations for repeatability and reproducibility (RSD(r) and RSD(R)) were calculated. The results showed that not only the PCR reaction but also the factors 'DNA isolation' and 'PCR day' are important factors for the total variance and should therefore be included in the in-house validation. It is proposed to use a statistical model to estimate these factors from a large dataset of initial validations so that for similar GMO methods in the future, only the PCR step needs to be validated. The resulting data are discussed in the light of agreed European criteria for qualified GMO detection methods.

  11. Validity of the remote food photography method against doubly labeled water among minority preschoolers

    Science.gov (United States)

    The aim of this study was to determine the validity of energy intake (EI) estimations made using the remote food photography method (RFPM) compared to the doubly labeled water (DLW) method in minority preschool children in a free-living environment. Seven days of food intake and spot urine samples...

  12. Validity of a structured method of selecting abstracts for a plastic surgical scientific meeting

    NARCIS (Netherlands)

    van der Steen, LPE; Hage, JJ; Kon, M; Monstrey, SJ

    In 1999, the European Association of Plastic Surgeons accepted a structured method to assess and select the abstracts that are submitted for its yearly scientific meeting. The two criteria used to evaluate whether such a selection method is accurate were reliability and validity. The authors

  13. Increased efficacy for in-house validation of real-time PCR GMO detection methods

    NARCIS (Netherlands)

    Scholtens-Toma, I.M.J.; Kok, E.J.; Hougs, L.; Molenaar, B.; Thissen, J.T.N.M.; Voet, van der H.

    2010-01-01

    To improve the efficacy of the in-house validation of GMO detection methods (DNA isolation and real-time PCR, polymerase chain reaction), a study was performed to gain insight in the contribution of the different steps of the GMO detection method to the repeatability and in-house reproducibility. In

  14. Experimental validation for calcul methods of structures having shock non-linearity

    International Nuclear Information System (INIS)

    Brochard, D.; Buland, P.

    1987-01-01

    For the seismic analysis of non-linear structures, numerical methods have been developed which need to be validated on experimental results. The aim of this paper is to present the design method of a test program which results will be used for this purpose. Some applications to nuclear components will illustrate this presentation [fr

  15. Introduction to Validation of Analytical Methods: Potentiometric Determination of CO[subscript 2

    Science.gov (United States)

    Hipólito-Nájera, A. Ricardo; Moya-Hernandez, M. Rosario; Gomez-Balderas, Rodolfo; Rojas-Hernandez, Alberto; Romero-Romo, Mario

    2017-01-01

    Validation of analytical methods is a fundamental subject for chemical analysts working in chemical industries. These methods are also relevant for pharmaceutical enterprises, biotechnology firms, analytical service laboratories, government departments, and regulatory agencies. Therefore, for undergraduate students enrolled in majors in the field…

  16. Development and Validation of a RP-HPLC Method for the ...

    African Journals Online (AJOL)

    Purpose: To develop and validate a sensitive HPLC method for the separation and simultaneous estimation of two ingredients in a composition comprising of rifampicin and a flavonoid glycoside (an enhancer of oral bioavailability of rifampicin). Methods: Reverse phase (RP) chromatographic separation and estimation was ...

  17. Comprehensive validation scheme for in situ fiber optics dissolution method for pharmaceutical drug product testing.

    Science.gov (United States)

    Mirza, Tahseen; Liu, Qian Julie; Vivilecchia, Richard; Joshi, Yatindra

    2009-03-01

    There has been a growing interest during the past decade in the use of fiber optics dissolution testing. Use of this novel technology is mainly confined to research and development laboratories. It has not yet emerged as a tool for end product release testing despite its ability to generate in situ results and efficiency improvement. One potential reason may be the lack of clear validation guidelines that can be applied for the assessment of suitability of fiber optics. This article describes a comprehensive validation scheme and development of a reliable, robust, reproducible and cost-effective dissolution test using fiber optics technology. The test was successfully applied for characterizing the dissolution behavior of a 40-mg immediate-release tablet dosage form that is under development at Novartis Pharmaceuticals, East Hanover, New Jersey. The method was validated for the following parameters: linearity, precision, accuracy, specificity, and robustness. In particular, robustness was evaluated in terms of probe sampling depth and probe orientation. The in situ fiber optic method was found to be comparable to the existing manual sampling dissolution method. Finally, the fiber optic dissolution test was successfully performed by different operators on different days, to further enhance the validity of the method. The results demonstrate that the fiber optics technology can be successfully validated for end product dissolution/release testing. (c) 2008 Wiley-Liss, Inc. and the American Pharmacists Association

  18. Validity and reliability of the HEMPA method for patient handling assessment.

    Science.gov (United States)

    Villarroya, A; Arezes, P; Díaz de Freijo, S; Fraga, F

    2017-11-01

    Specific methods currently exist to assess occupational hazards resulting from patient handling in the healthcare sector, according to ISO/TR 12296. They are all similar in nature, but with a different analysis perspective; for that reason a comparison of the most relevant methods was performed in a previous research. As a result, a basis of a new tool that integrates the complementary aspects of those methods was proposed. To verify the validity and reliability of that method, a study within a hospital setting was carried out in five medical and surgical units of a public health institution. Based on the obtained results, the analysed method (called HEMPA) proved to be valid and reliable. Also, this method reflects a positive correlation between risk and damage and correctly quantifies risks regarding patient's dependence. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Rapid Determination of Isomeric Benzoylpaeoniflorin and Benzoylalbiflorin in Rat Plasma by LC-MS/MS Method

    Directory of Open Access Journals (Sweden)

    Chuanqi Zhou

    2017-01-01

    Full Text Available Benzoylpaeoniflorin (BP is a potential therapeutic agent against oxidative stress related Alzheimer’s disease. In this study, a more rapid, selective, and sensitive liquid chromatography-tandem mass spectrometric (LC-MS/MS method was developed to determine BP in rat plasma distinguishing with a monoterpene isomer, benzoylalbiflorin (BA. The method showed a linear response from 1 to 1000 ng/mL (r>0.9950. The precision of the interday and intraday ranged from 2.03 to 12.48% and the accuracy values ranged from −8.00 to 10.33%. Each running of the method could be finished in 4 minutes. The LC-MS/MS method was validated for specificity, linearity, precision, accuracy, recovery, and stability and was found to be acceptable for bioanalytical application. Finally, this fully validated method was successfully applied to a pharmacokinetic study in rats following oral administration.

  20. Comparing Thermal Process Validation Methods for Salmonella Inactivation on Almond Kernels.

    Science.gov (United States)

    Jeong, Sanghyup; Marks, Bradley P; James, Michael K

    2017-01-01

    Ongoing regulatory changes are increasing the need for reliable process validation methods for pathogen reduction processes involving low-moisture products; however, the reliability of various validation methods has not been evaluated. Therefore, the objective was to quantify accuracy and repeatability of four validation methods (two biologically based and two based on time-temperature models) for thermal pasteurization of almonds. Almond kernels were inoculated with Salmonella Enteritidis phage type 30 or Enterococcus faecium (NRRL B-2354) at ~10 8 CFU/g, equilibrated to 0.24, 0.45, 0.58, or 0.78 water activity (a w ), and then heated in a pilot-scale, moist-air impingement oven (dry bulb 121, 149, or 177°C; dew point Salmonella inactivation using a traditional (D, z) model and a modified model accounting for process humidity. Among the process validation methods, both methods based on time-temperature models had better repeatability, with replication errors approximately half those of the surrogate ( E. faecium ). Additionally, the modified model yielded the lowest root mean squared error in predicting Salmonella inactivation (1.1 to 1.5 log CFU/g); in contrast, E. faecium yielded a root mean squared error of 1.2 to 1.6 log CFU/g, and the traditional model yielded an unacceptably high error (3.4 to 4.4 log CFU/g). Importantly, the surrogate and modified model both yielded lethality predictions that were statistically equivalent (α = 0.05) to actual Salmonella lethality. The results demonstrate the importance of methodology, a w , and process humidity when validating thermal pasteurization processes for low-moisture foods, which should help processors select and interpret validation methods to ensure product safety.

  1. Validation of Immunomonitoring Methods for Application in Clinical Studies: The HLA-Peptide Multimer Staining Assay.

    Science.gov (United States)

    Chandran, P Anoop; Laske, Karoline; Cazaly, Angelica; Rusch, Elisa; Schmid-Horch, Barbara; Rammensee, Hans-Georg; Ottensmeier, Christian H; Gouttefangeas, Cécile

    2018-03-01

    Validated assays are essential to generate data with defined specificity, consistency, and reliability. Although the process of validation is required for applying immunoassays in the context of clinical studies, reports on systematic validation of in vitro T cell assays are scarce so far. We recently validated our HLA-peptide multimer staining assay in a systematic manner so as to qualify the method for monitoring antigen-specific T cell responses after immunotherapy. Parameters of the assay, specificity, precision, linearity, sensitivity, and robustness were assessed systematically. Experiments were designed to address specifically each parameter and are detailed. Nonspecific multimer staining was below the acceptance limit of 0.02% multimer (+) CD8 (+) cells. The assay showed acceptable precision in all dimensions it was repeated (CV  0.99) of antigen specific cells. We succeeded in validating the HLA-multimer staining assay in a systematic manner. Additionally, we propose a technical framework and recommendations that can be applied for validating other T cell assessment methods. © 2016 International Clinical Cytometry Society. © 2016 International Clinical Cytometry Society.

  2. Reliability and Validity of the Footprint Assessment Method Using Photoshop CS5 Software.

    Science.gov (United States)

    Gutiérrez-Vilahú, Lourdes; Massó-Ortigosa, Núria; Costa-Tutusaus, Lluís; Guerra-Balic, Myriam

    2015-05-01

    Several sophisticated methods of footprint analysis currently exist. However, it is sometimes useful to apply standard measurement methods of recognized evidence with an easy and quick application. We sought to assess the reliability and validity of a new method of footprint assessment in a healthy population using Photoshop CS5 software (Adobe Systems Inc, San Jose, California). Forty-two footprints, corresponding to 21 healthy individuals (11 men with a mean ± SD age of 20.45 ± 2.16 years and 10 women with a mean ± SD age of 20.00 ± 1.70 years) were analyzed. Footprints were recorded in static bipedal standing position using optical podography and digital photography. Three trials for each participant were performed. The Hernández-Corvo, Chippaux-Smirak, and Staheli indices and the Clarke angle were calculated by manual method and by computerized method using Photoshop CS5 software. Test-retest was used to determine reliability. Validity was obtained by intraclass correlation coefficient (ICC). The reliability test for all of the indices showed high values (ICC, 0.98-0.99). Moreover, the validity test clearly showed no difference between techniques (ICC, 0.99-1). The reliability and validity of a method to measure, assess, and record the podometric indices using Photoshop CS5 software has been demonstrated. This provides a quick and accurate tool useful for the digital recording of morphostatic foot study parameters and their control.

  3. Performance Validity Testing in Neuropsychology: Methods for Measurement Development and Maximizing Diagnostic Accuracy.

    Science.gov (United States)

    Wodushek, Thomas R; Greher, Michael R

    2017-05-01

    In the first column in this 2-part series, Performance Validity Testing in Neuropsychology: Scientific Basis and Clinical Application-A Brief Review, the authors introduced performance validity tests (PVTs) and their function, provided a justification for why they are necessary, traced their ongoing endorsement by neuropsychological organizations, and described how they are used and interpreted by ever increasing numbers of clinical neuropsychologists. To enhance readers' understanding of these measures, this second column briefly describes common detection strategies used in PVTs as well as the typical methods used to validate new PVTs and determine cut scores for valid/invalid determinations. We provide a discussion of the latest research demonstrating how neuropsychologists can combine multiple PVTs in a single battery to improve sensitivity/specificity to invalid responding. Finally, we discuss future directions for the research and application of PVTs.

  4. Method development, validation and stability study of ritonavir in bulk and pharmaceutical dosage form by spectrophotometric method

    Directory of Open Access Journals (Sweden)

    Anindita Behera

    2011-01-01

    Full Text Available Background: Ritonavir is a protease inhibitor and mostly used as a booster for increasing the bioavailability of other protease inhibitors like Atazanavir Sulfate and Lopinavir. Aims: Quality assessment of the new dosage form of Ritonavir i.e. tablets is very essential, so two sensitive, simple and precise methods are developed for quantification of Ritonavir in bulk and tablet dosage forms. Materials and Methods: The first method is based on first order derivative method and the second is based on area under curve method. Both the methods are validated according to international conference of harmonization (ICH guidelines. A stability study of Ritonavir is done in UV - Visible Spectrophotometer under different stress conditions recommended by ICH guidelines. Results: The absorption maximum is found to be 239nm in methanol. The absorption maximum in first method is chosen at 253.2nm, and the linearity is found between 4 - 20 ΅g/ml with coefficient of correlation value 0.9981. In the second method, the range for area under curve selected is 237 - 242nm. The linearity is found between 4 -20 ΅g/ml with coefficient of correlation value 0.9992. Conclusion: The developed methods are validated and found to be simple, rapid, precise and cost-effective. The degradation study in tablet dosage form can be used as a stability indicating assay method.

  5. The Validation of Atomic Absorption Spectrometry (AAS) Method for the Determination of Cr, Cu and Pb

    International Nuclear Information System (INIS)

    Purwanto, A.; Supriyanto, C.; Samin P

    2007-01-01

    The validation of analytical method of atomic absorption spectrometry for the determination of Cr, Cu and Pb by using certified reference materials (CRM) have been carried out. The validation of analytical method was done by measurement of precision, accuracy, bias, % D and % RSD by analysis of chromium (Cr), Copper (Cu), and Lead (Pb) elements in CRM samples. Soil-7 is weighted and dissolved 0.3337 gram to use the bomb digester with concentrated nitric acid, perchloric acid, fluoric acid, and than solution to vinal volume is 10 mL with aquabidest. The validity of instrument atomic absorption spectrometer still valid with obtained of accuracy is 95.85 % and precision is 2.86 for Cr.; 103.32 % and 0.45 for Cu., 114.14 % and 9.89 for Pb. The validation of analytical method showed that with obtained of the content of Cr, Cu and Pb elements is 57.51, 11.37 and 68.49 μg/g., this result is still in the range concentration of certificate. (author)

  6. Validation of spectrophotometric microplate methods for polyphenol oxidase and peroxidase activities analysis in fruits and vegetables

    Directory of Open Access Journals (Sweden)

    Érica Sayuri SIGUEMOTO

    Full Text Available Abstract Enzymes polyphenol oxidase (PPO and peroxidase (POD play important roles in the processing of fruits and vegetables, since they can produce undesirable changes in color, texture and flavor. Classical methods of activity assessment are based on cuvette spectrophotometric readings. This work aims to propose, to validate and to test microplate spectrophotometric methods. Samples of apple juice and lyophilized enzymes from mushroom and horseradish were analyzed by the cuvette and microplate methods and it was possible to validate the microplate assays with satisfactory results regarding linearity, repeatability, accuracy along with quantitation and detection limits. The proposed microplate methods proved to be reliable and reproducible as the classical methods besides having the advantages of allowing simultaneous analysis and requiring a reduced amount of samples and reactants, which can beneficial to the study of enzyme inactivation in the processing of fruits and vegetables.

  7. Chemical analysis of solid residue from liquid and solid fuel combustion: Method development and validation

    Energy Technology Data Exchange (ETDEWEB)

    Trkmic, M. [University of Zagreb, Faculty of Mechanical Engineering and Naval Architecturek Zagreb (Croatia); Curkovic, L. [University of Zagreb, Faculty of Chemical Engineering and Technology, Zagreb (Croatia); Asperger, D. [HEP-Proizvodnja, Thermal Power Plant Department, Zagreb (Croatia)

    2012-06-15

    This paper deals with the development and validation of methods for identifying the composition of solid residue after liquid and solid fuel combustion in thermal power plant furnaces. The methods were developed for energy dispersive X-ray fluorescence (EDXRF) spectrometer analysis. Due to the fuels used, the different composition and the location of creation of solid residue, it was necessary to develop two methods. The first method is used for identifying solid residue composition after fuel oil combustion (Method 1), while the second method is used for identifying solid residue composition after the combustion of solid fuels, i. e. coal (Method 2). Method calibration was performed on sets of 12 (Method 1) and 6 (Method 2) certified reference materials (CRM). CRMs and analysis test samples were prepared in pellet form using hydraulic press. For the purpose of method validation the linearity, accuracy, precision and specificity were determined, and the measurement uncertainty of methods for each analyte separately was assessed. The methods were applied in the analysis of real furnace residue samples. (Copyright copyright 2012 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

  8. Best Practices in Stability Indicating Method Development and Validation for Non-clinical Dose Formulations.

    Science.gov (United States)

    Henry, Teresa R; Penn, Lara D; Conerty, Jason R; Wright, Francesca E; Gorman, Gregory; Pack, Brian W

    2016-11-01

    Non-clinical dose formulations (also known as pre-clinical or GLP formulations) play a key role in early drug development. These formulations are used to introduce active pharmaceutical ingredients (APIs) into test organisms for both pharmacokinetic and toxicological studies. Since these studies are ultimately used to support dose and safety ranges in human studies, it is important to understand not only the concentration and PK/PD of the active ingredient but also to generate safety data for likely process impurities and degradation products of the active ingredient. As such, many in the industry have chosen to develop and validate methods which can accurately detect and quantify the active ingredient along with impurities and degradation products. Such methods often provide trendable results which are predictive of stability, thus leading to the name; stability indicating methods. This document provides an overview of best practices for those choosing to include development and validation of such methods as part of their non-clinical drug development program. This document is intended to support teams who are either new to stability indicating method development and validation or who are less familiar with the requirements of validation due to their position within the product development life cycle.

  9. Validated spectrofluorimetric method for the determination of clonazepam in pharmaceutical preparations.

    Science.gov (United States)

    Ibrahim, Fawzia; El-Enany, Nahed; Shalan, Shereen; Elsharawy, Rasha

    2016-05-01

    A simple, highly sensitive and validated spectrofluorimetric method was applied in the determination of clonazepam (CLZ). The method is based on reduction of the nitro group of clonazepam with zinc/CaCl2, and the product is then reacted with 2-cyanoacetamide (2-CNA) in the presence of ammonia (25%) yielding a highly fluorescent product. The produced fluorophore exhibits strong fluorescence intensity at ʎ(em) = 383 nm after excitation at ʎ(ex) = 333 nm. The method was rectilinear over a concentration range of 0.1-0.5 ng/mL with a limit of detection (LOD) of 0.0057 ng/mL and a limit of quantification (LOQ) of 0.017 ng/mL. The method was fully validated and successfully applied to the determination of CLZ in its tablets with a mean percentage recovery of 100.10 ± 0.75%. Method validation according to ICH Guidelines was evaluated. Statistical analysis of the results obtained using the proposed method was successfully compared with those obtained using a reference method, and there was no significance difference between the two methods in terms of accuracy and precision. Copyright © 2015 John Wiley & Sons, Ltd.

  10. Development and validation of stability indicating UPLC assay method for ziprasidone active pharma ingredient

    Directory of Open Access Journals (Sweden)

    Sonam Mittal

    2012-01-01

    Full Text Available Background: Ziprasidone, a novel antipsychotic, exhibits a potent highly selective antagonistic activity on D2 and 5HT2A receptors. Literature survey for ziprasidone revealed several analytical methods based on different techniques but no UPLC method has been reported so far. Aim: Aim of this research paper is to present a simple and rapid stability indicating isocratic, ultra performance liquid chromatographic (UPLC method which was developed and validated for the determination of ziprasidone active pharmaceutical ingredient. Forced degradation studies of ziprasidone were studied under acid, base, oxidative hydrolysis, thermal stress and photo stress conditions. Materials and Methods: The quantitative determination of ziprasidone drug was performed on a Supelco analytical column (100×2.1 mm i.d., 2.7 ΅m with 10 mM ammonium acetate buffer (pH: 6.7 and acetonitrile (ACN as mobile phase with the ratio (55:45-Buffer:ACN at a flow rate of 0.35 ml/ min. For UPLC method, UV detection was made at 318 nm and the run time was 3 min. Developed UPLC method was validated as per ICH guidelines. Results and Conclusion: Mild degradation of the drug substance was observed during oxidative hydrolysis and considerable degradation observed during basic hydrolysis. During method validation, parameters such as precision, linearity, ruggedness, stability, robustness, and specificity were evaluated, which remained within acceptable limits. Developed UPLC method was successfully applied for evaluating assay of Ziprasidone active Pharma ingredient.

  11. Surface Modification of Photoresist SU-8 for Low Autofluorescence and Bioanalytical Applications

    DEFF Research Database (Denmark)

    Cao, Cuong; Birtwell, Sam W.; Høgberg, Jonas

    2011-01-01

    This paper reports a surface modification of epoxy-based negative photoresist SU-8 for reducing its autofluorescence while enhancing its biofunctionality. By covalently depositing a thin layer of 20 nm Au nanoparticles (AuNPs) onto the SU-8 surface, we found that the AuNPs-coated SU-8 surface...... is much less fluorescent than the untreated SU-8. Moreover, DNA probes can easily be immobilized on the Au surface and are thermally stable over a wide range of temperature. These improvements will benefit bioanalytical applications such as DNA hybridization and solid-phase PCR (SP-PCR)....

  12. The Bio-Analytic Resource: Data visualization and analytic tools for multiple levels of plant biology

    Directory of Open Access Journals (Sweden)

    Jamie Waese

    2016-11-01

    Full Text Available The Bio-Analytic Resource for Plant Biology (BAR is a portal for accessing large data sets from approximately 15 different plant species, with a focus on transcriptomic, protein-protein interaction, and promoter data. It consists of numerous databases for which its curators have added useful metadata, data visualization tools to display the query results from these databases, and visual analytic tools to identify e.g. gene expression patterns of interest based on publicly-available data. We briefly cover some of these tools and scenarios in which they might be useful for plant researchers.

  13. Validation of methods for measurement of insulin secretion in humans in vivo

    DEFF Research Database (Denmark)

    Kjems, L L; Christiansen, E; Vølund, A

    2000-01-01

    )-considered the "gold standard"-and the combined model (by Vølund et al.). The deconvolution method is a 2-day method, which generally requires separate assessment of C-peptide kinetics, whereas the combined model is a single-day method that uses insulin and C-peptide data from a single test of interest. The validity...... the combined model and the deconvolution method were accurate, i.e., recovery of true ISR was not significantly different from 100%. Furthermore, both maximal and total ISRs from the combined model were strongly correlated to those obtained by the deconvolution method (r = 0.89 and r = 0.82, respectively...

  14. Validation of methods used in the Florida Department of Agricultural and Consumer Services' Chemical Residue Laboratory.

    Science.gov (United States)

    Parker, G A

    1991-01-01

    Very few methods for detecting residues of pesticides in food or agricultural samples have undergone rigorous colloborative study and possess official AOAC status. The Chemical Residue Laboratory has formalized a method validation scheme to use when incorporating or developing new, unofficial methods. These methods are validated by assessing certain performance parameters: scope, specificity, linear range, accuracy, precision, limit of detection (LOD), and limit of quantitation (LOQ). For accuracy and precision assessment, 12 replicate fortifications must yield recoveries within the range of 70-120% with a coefficient of variation (CV) that compares favorably to the Horwitz CV. LOD and LOQ are equivalent to 3 and 10 times, respectively, the background signal contributed by a sample matrix blank. This criterion that we use for LOD/LOQ is not universal. In fact, because of differing definitions, we have encountered difficulties in enforcing a tolerance by using a registrant's method. This paper also presents an example of our method validation scheme, using a recent method development project for detecting sulfamethazine in raw milk. The sulfamethazine project also revealed unanticipated personnel problems, underscoring the importance of the human factor in quality assurance.

  15. Validity and reliability of a method for assessment of cervical vertebral maturation.

    Science.gov (United States)

    Zhao, Xiao-Guang; Lin, Jiuxiang; Jiang, Jiu-Hui; Wang, Qingzhu; Ng, Sut Hong

    2012-03-01

    To evaluate the validity and reliability of the cervical vertebral maturation (CVM) method with a longitudinal sample. Eighty-six cephalograms from 18 subjects (5 males and 13 females) were selected from the longitudinal database. Total mandibular length was measured on each film; an increased rate served as the gold standard in examination of the validity of the CVM method. Eleven orthodontists, after receiving intensive training in the CVM method, evaluated all films twice. Kendall's W and the weighted kappa statistic were employed. Kendall's W values were higher than 0.8 at both times, indicating strong interobserver reproducibility, but interobserver agreement was documented twice at less than 50%. A wide range of intraobserver agreement was noted (40.7%-79.1%), and substantial intraobserver reproducibility was proved by kappa values (0.53-0.86). With regard to validity, moderate agreement was reported between the gold standard and observer staging at the initial time (kappa values 0.44-0.61). However, agreement seemed to be unacceptable for clinical use, especially in cervical stage 3 (26.8%). Even though the validity and reliability of the CVM method proved statistically acceptable, we suggest that many other growth indicators should be taken into consideration in evaluating adolescent skeletal maturation.

  16. Validation of methods for the detection and quantification of engineered nanoparticles in food

    DEFF Research Database (Denmark)

    Linsinger, T.P.J.; Chaudhry, Q.; Dehalu, V.

    2013-01-01

    The potential impact of nanomaterials on the environment and on human health has already triggered legislation requiring labelling of products containing nanoparticles. However, so far, no validated analytical methods for the implementation of this legislation exist. This paper outlines a generic...

  17. Validity of a Simulation Game as a Method for History Teaching

    Science.gov (United States)

    Corbeil, Pierre; Laveault, Dany

    2011-01-01

    The aim of this research is, first, to determine the validity of a simulation game as a method of teaching and an instrument for the development of reasoning and, second, to study the relationship between learning and students' behavior toward games. The participants were college students in a History of International Relations course, with two…

  18. Validation of methods for the detection and quantification of engineered nanoparticles in food

    NARCIS (Netherlands)

    Linsinger, T.P.J.; Chaudhry, Q.; Dehalu, V.; Delahaut, P.; Dudkiewicz, A.; Grombe, R.; Kammer, von der F.; Larsen, E.H.; Legros, S.; Loeschner, K.; Peters, R.; Ramsch, R.; Roebben, G.; Tiede, K.; Weigel, S.

    2013-01-01

    The potential impact of nanomaterials on the environment and on human health has already triggered legislation requiring labelling of products containing nanoparticles. However, so far, no validated analytical methods for the implementation of this legislation exist. This paper outlines a generic

  19. A validation framework for microbial forensic methods based on statistical pattern recognition

    Energy Technology Data Exchange (ETDEWEB)

    Velsko, S P

    2007-11-12

    This report discusses a general approach to validating microbial forensic methods that attempt to simultaneously distinguish among many hypotheses concerning the manufacture of a questioned biological agent sample. It focuses on the concrete example of determining growth medium from chemical or molecular properties of a bacterial agent to illustrate the concepts involved.

  20. Validation of the DLW method in Japanese quail at different water fluxes using laser and IRMS

    NARCIS (Netherlands)

    van Trigt, R; Kerstel, E.R.T.; Neubert, R.E.M.; Meijer, H.A.J.; Mclean, M.; Visser, G.H.

    2002-01-01

    In Japanese quail (Coturnix c. japonica; n = 9), the doubly labeled water (DLW) method (H-2, O-18) for estimation Of CO2 production (1/day) was validated. To evaluate its sensitivity to water efflux levels (r(H2Oe); g/day) and to assumptions of fractional evaporative water loss (x; dimensionless),

  1. Validation of a method to predict hammer speed from cable force

    Directory of Open Access Journals (Sweden)

    Sara M. Brice

    2015-09-01

    Conclusion: This study successfully derived and validated a method that allows prediction of linear hammer speed from directly measured cable force data. Two linear regression models were developed and it was found that either model would be capable of predicting accurate speeds. However, data predicted using the shifted regression model were more accurate.

  2. Validation of the ultraviolet spectrophotometry method for the quality control of ciprofloxacin chlorhydrate in Ciprecu tablets

    International Nuclear Information System (INIS)

    Perez Navarro, Maikel; Rodriguez Hernandez, Yaslenis; Suarez Perez, Yania

    2014-01-01

    Quinolones are a group of antimicrobials of high clinical significance. Ciprofloxacin hydrochloride monohydrate is a second-generation antibacterial fluoroquinolone for treatment of several infections and is marketed as eye drops, injections, capsule and tablets. To develop and to validate an ultraviolet spectrophotometric analytical method to be used in the quality control of ciprofloxacin hydrochloride monohydrate in newly manufactured Ciprecu tablets

  3. A simple method for validation and verification of pipettes mounted on automated liquid handlers

    DEFF Research Database (Denmark)

    Stangegaard, Michael; Hansen, Anders Johannes; Frøslev, Tobias G

    2011-01-01

    are freely available. In conclusion, we have set up a simple, inexpensive, and fast solution for the continuous validation of ALHs used for accredited work according to the ISO 17025 standard. The method is easy to use for aqueous solutions but requires a spectrophotometer that can read microtiter plates....

  4. Validation of the actuator line method using near wake measurements of the MEXICO rotor

    DEFF Research Database (Denmark)

    Nilsson, Karl; Shen, Wen Zhong; Sørensen, Jens Nørkær

    2015-01-01

    The purpose of the present work is to validate the capability of the actuator line method to compute vortex structures in the near wake behind the MEXICO experimental wind turbine rotor. In the MEXICO project/MexNext Annex, particle image velocimetry measurements have made it possible to determine...

  5. Alternative method to validate the seasonal land cover regions of the conterminous United States

    Science.gov (United States)

    Zhiliang Zhu; Donald O. Ohlen; Raymond L. Czaplewski; Robert E. Burgan

    1996-01-01

    An accuracy assessment method involving double sampling and the multivariate composite estimator has been used to validate the prototype seasonal land cover characteristics database of the conterminous United States. The database consists of 159 land cover classes, classified using time series of 1990 1-km satellite data and augmented with ancillary data including...

  6. Methods and procedures for the verification and validation of artificial neural networks

    CERN Document Server

    Taylor, Brian J

    2006-01-01

    Neural networks are members of a class of software that have the potential to enable intelligent computational systems capable of simulating characteristics of biological thinking and learning. This volume introduces some of the methods and techniques used for the verification and validation of neural networks and adaptive systems.

  7. The initial conditions of observed star clusters - I. Method description and validation

    NARCIS (Netherlands)

    Pijloo, J.T.; Portegies Zwart, S.F.; Alexander, P.E.R.; Gieles, M.; Larsen, S.S.; Groot, P.J.; Devecchi, B.A.

    2015-01-01

    We have coupled a fast, parametrized star cluster evolution code to a Markov Chain Monte Carlo code to determine the distribution of probable initial conditions of observed star clusters, that may serve as a starting point for future N-body calculations. In this paper, we validate our method by

  8. Development and Validation of a RP-HPLC Method for Assay of ...

    African Journals Online (AJOL)

    Evaluation of system suitability parameters. System suitability variables and their optimization are vital in RP liquid chromatographic method. The individual parameters were validated in triplicate injections (n = 3) of standard solution (1. µg/mL) using Agilent series 1200 HPLC instrument with Eclipse XDB® column 5 µm (4.6 ...

  9. Validation of Experimental whole-body SAR Assessment Method in a Complex Indoor Environment

    DEFF Research Database (Denmark)

    Bamba, Aliou; Joseph, Wout; Vermeeren, Gunter

    2012-01-01

    Assessing experimentally the whole-body specific absorption rate (SARwb) in a complex indoor environment is very challenging. An experimental method based on room electromagnetics theory (accounting only the Line-Of-Sight as specular path) to assess the whole-body SAR is validated by numerical...... simulations with the Finite-Difference Time-Domain method. Furthermore, the method accounts for the diffuse multipath components (DMC) in the total absorption rate by considering the reverberation time of the investigated room, which describes all the losses in a complex indoor environment. The advantage...... of the proposed method is that it allows discarding the computation burden because it does not use any discretizations. Results show good agreement between measurement and computation at 2.8 GHz, as long as the plane wave assumption is valid, i.e., for high distances from the transmitter. Relative deviations 0...

  10. Rationale and methods of the European Food Consumption Validation (EFCOVAL) Project

    DEFF Research Database (Denmark)

    de Boer, E. J.; Slimani, N.; van 't Veer, P.

    2011-01-01

    the EPIC-Soft databases were adapted. Finally, the EFCOVAL Consortium developed a statistical tool (Multiple Source Method) for estimating the usual intake and distribution, which has been tested using real food consumption data and compared with three other statistical methods through a simulation study......Background/Objectives: The overall objective of the European Food Consumption Validation (EFCOVAL) Project was to further develop and validate a trans-European food consumption method to be used for the evaluation of the intake of foods, nutrients and potentially hazardous chemicals within...... the European population. Subjects/Methods: The EFCOVAL Project was carried out by 13 institutes from 11 European countries. The main activities were centered on the three main objectives of the project organized in different sub-projects. Results: In EFCOVAL, EPIC-Soft (the software developed to conduct 24-h...

  11. Low-cost extrapolation method for maximal LTE radio base station exposure estimation: test and validation.

    Science.gov (United States)

    Verloock, Leen; Joseph, Wout; Gati, Azeddine; Varsier, Nadège; Flach, Björn; Wiart, Joe; Martens, Luc

    2013-06-01

    An experimental validation of a low-cost method for extrapolation and estimation of the maximal electromagnetic-field exposure from long-term evolution (LTE) radio base station installations are presented. No knowledge on downlink band occupation or service characteristics is required for the low-cost method. The method is applicable in situ. It only requires a basic spectrum analyser with appropriate field probes without the need of expensive dedicated LTE decoders. The method is validated both in laboratory and in situ, for a single-input single-output antenna LTE system and a 2×2 multiple-input multiple-output system, with low deviations in comparison with signals measured using dedicated LTE decoders.

  12. Validation of three new methods for determination of metal emissions using a modified Environmental Protection Agency Method 301

    Energy Technology Data Exchange (ETDEWEB)

    Catherine A. Yanca; Douglas C. Barth; Krag A. Petterson; Michael P. Nakanishi; John A. Cooper; Bruce E. Johnsen; Richard H. Lambert; Daniel G. Bivins [Cooper Environmental Services, LLC, Portland, OR (United States)

    2006-12-15

    Three new methods applicable to the determination of hazardous metal concentrations in stationary source emissions were developed and evaluated for use in U.S. Environmental Protection Agency (EPA) compliance applications. Two of the three independent methods, a continuous emissions monitor-based method (Xact) and an X-ray-based filter method (XFM), are used to measure metal emissions. The third method involves a quantitative aerosol generator (QAG), which produces a reference aerosol used to evaluate the measurement methods. A modification of EPA Method 301 was used to validate the three methods for As, Cd, Cr, Pb, and Hg, representing three hazardous waste combustor Maximum Achievable Control Technology (MACT) metal categories (low volatile, semivolatile, and volatile). The measurement methods were evaluated at a hazardous waste combustor (HWC) by comparing measured with reference aerosol concentrations. The QAG, Xact, and XFM met the modified Method 301 validation criteria. All three of the methods demonstrated precisions and accuracies on the order of 5%. The measurement methods should be applicable to emissions from a wide range of sources, and the reference aerosol generator should be applicable to additional analytes. EPA recently approved an alternative monitoring petition for an HWC at Eli Lilly's Tippecanoe site in Lafayette, IN, in which the Xact is used for demonstrating compliance with the HWC MACT metal emissions (low volatile, semivolatile, and volatile). The QAG reference aerosol generator was approved as a method for providing a quantitative reference aerosol, which is required for certification and continuing quality assurance of the Xact. 30 refs., 5 figs., 11 tabs.

  13. Validation of the quality control methods for active ingredients of Fungirex cream

    International Nuclear Information System (INIS)

    Perez Navarro, Maikel; Rodriguez Hernandez, Yaslenis; Suarez Perez, Yania

    2014-01-01

    Fungirex cream is a two-drug product, that is, undecylenic acid and zinc undecylenate over a suitable basis. Since this is a product not documented in the official monographs of the pharmacopoeia, simple analytical methods were suggested for quantitation of analytes of interest in the cream, which are useful for release of newly prepared cream batches. To validate two volumetric methods for the quality control of active ingredients in Fungirex cream

  14. Validating Computer Security Methods: Meta-methodology for an Adversarial Science

    OpenAIRE

    Roque, Antonio

    2017-01-01

    How can we justify the validity of our computer security methods? This meta-methodological question is related to recent explorations on the science of computer security, which have been hindered by computer security's unique properties. We confront this by developing a taxonomy of properties and methods. Interdisciplinary foundations provide a solid grounding for a set of essential concepts, including a decision tree for characterizing adversarial interaction. Several types of invalidation a...

  15. Validation of uncertainty of weighing in the preparation of radionuclide standards by Monte Carlo Method

    International Nuclear Information System (INIS)

    Cacais, F.L.; Delgado, J.U.; Loayza, V.M.

    2016-01-01

    In preparing solutions for the production of radionuclide metrology standards is necessary measuring the quantity Activity by mass. The gravimetric method by elimination is applied to perform weighing with smaller uncertainties. At this work is carried out the validation, by the Monte Carlo method, of the uncertainty calculation approach implemented by Lourenco and Bobin according to ISO GUM for the method by elimination. The results obtained by both uncertainty calculation methods were consistent indicating that were fulfilled the conditions for the application of ISO GUM in the preparation of radioactive standards. (author)

  16. Validity and reliability of autofluorescence-based quantification method of dental plaque.

    Science.gov (United States)

    Han, Sun-Young; Kim, Bo-Ra; Ko, Hae-Youn; Kwon, Ho-Keun; Kim, Baek-Il

    2015-12-01

    The aim of this study was to evaluate validity and reliability of autofluorescence-based plaque quantification (APQ) method. The facial surfaces of 600 sound anterior teeth of 50 subjects were examined. The subjects received dental plaque examination using Turesky modified Quigley Hein plaque index (QHI) and Silness & Löe plaque index (SLI). The autofluorescence images were taken before the plaque examination with Quantitative Light-induced Fluorescence-Digital, and plaque percent index (PPI) was calculated. Correlation between two existing plaque indices and the PPI of the APQ method was evaluated to find which level of plaque redness on tooth (ΔR) by the APQ method shows the highest correlation. The area under the ROC curve (AUC) analysis and intra- and inter-examiner reliability tests were performed. The PPIΔR20 of the APQ method showed a moderate correlation with two existing plaque indices (rho of QHI=0.48, SLI=0.51). This methodology fell in the fair category and it had an excellent reliability. The APQ method also showed possibility to detect heavy plaque with fair validity. The APQ method demonstrated excellent reliability, and fair validity, compared with 2 conventional indices. The plaque quantification described has the potential to be used in clinical evaluation of oral hygiene procedures. Copyright © 2015 Elsevier B.V. All rights reserved.

  17. Validation of ascorbic acid tablets of national production by igh-performance liquid chromatography method

    International Nuclear Information System (INIS)

    Rodriguez Hernandez, Yaslenis; Suarez Perez, Yania; Izquierdo Castro, Idalberto

    2009-01-01

    We validate an analytical method by high-performance liquid chromatography to determine ascorbic acid proportion in vitamin C tablets, which was designed as an alternative method to quality control and to follow-up of active principle chemical stability, since official techniques to quality control of ascorbic acid in tablets are not selective with degradation products. Method was modified according to that reported in USP 28, 2005 for analysis of injectable product. We used a RP-18 column of 250 x 4.6 mm 5 μm with a UV detector to 245 nm. Its validation was necessary for both objectives, considering parameters required for methods of I and II categories. This method was enough linear, exact, and precise in the rank of 100-300 μg/mL. Also, it was selective with remaining components of matrix and with the possible degradation products achieved in stressing conditions. Detection and quantification limits were estimated. When method was validated it was applied to ascorbic acid quantification in two batches of expired tablets and we detected a marked influence of container in active degradation principle after 12 months at room temperature. (Author)

  18. Pressurised liquid extraction of flavonoids in onions. Method development and validation

    DEFF Research Database (Denmark)

    Søltoft, Malene; Christensen, J.H.; Nielsen, J.

    2009-01-01

    A rapid and reliable analytical method for quantification of flavonoids in onions was developed and validated. Five extraction methods were tested on freeze-dried onions and subsequently high performance liquid chromatography (HPLC) with UV detection was used for quantification of seven flavonoids...... extraction methods. However. PLE was the preferred extraction method because the method can be highly automated, use only small amounts of solvents, provide the cleanest extracts, and allow the extraction of light and oxygen-sensitive flavonoids to be carried out in an inert atmosphere protected from light......-step PLE method showed good selectivity, precision (RSDs = 3.1-11%) and recovery of the extractable flavonoids (98-99%). The method also appeared to be a multi-method, i.e. generally applicable to, e.g. phenolic acids in potatoes and carrots....

  19. A Method for Ship Collision Damage and Energy Absorption Analysis and its Validation

    DEFF Research Database (Denmark)

    Zhang, Shengming; Pedersen, Preben Terndrup

    2017-01-01

    For design evaluation, there is a need for a method which is fast, practical and yet accurate enough to deter-mine the absorbed energy and collision damage extent in ship collision analysis. The most well-known sim-plified empirical approach to collision analysis was made probably by Minorsky...... is to re-examine thismethod’s validity and accuracy for ship collision damage analysis in ship design assessments by compre-hensive validations with experimental results from the public domain. In total, 20 experimental tests havebeen selected, analysed and compared with the results calculated using...

  20. Factor analysis methods and validity evidence: a review of instrument development across the medical education continuum.

    Science.gov (United States)

    Wetzel, Angela P

    2012-08-01

    Instrument development consistent with best practices is necessary for effective assessment and evaluation of learners and programs across the medical education continuum. The author explored the extent to which current factor analytic methods and other techniques for establishing validity are consistent with best practices. The author conducted electronic and hand searches of the English-language medical education literature published January 2006 through December 2010. To describe and assess current practices, she systematically abstracted reliability and validity evidence as well as factor analysis methods, data analysis, and reported evidence from instrument development articles reporting the application of exploratory factor analysis and principal component analysis. Sixty-two articles met eligibility criteria. They described 64 instruments and 95 factor analyses. Most studies provided at least one source of evidence based on test content. Almost all reported internal consistency, providing evidence based on internal structure. Evidence based on response process and relationships with other variables was reported less often, and evidence based on consequences of testing was not identified. Factor analysis findings suggest common method selection errors and critical omissions in reporting. Given the limited reliability and validity evidence provided for the reviewed instruments, educators should carefully consider the available supporting evidence before adopting and applying published instruments. Researchers should design for, test, and report additional evidence to strengthen the argument for reliability and validity of these measures for research and practice.

  1. A Bioanalytical Platform for Simultaneous Detection and Quantification of Biological Toxins

    Directory of Open Access Journals (Sweden)

    Hans Sigrist

    2012-02-01

    Full Text Available Prevalent incidents support the notion that toxins, produced by bacteria, fungi, plants or animals are increasingly responsible for food poisoning or intoxication. Owing to their high toxicity some toxins are also regarded as potential biological warfare agents. Accordingly, control, detection and neutralization of toxic substances are a considerable economic burden to food safety, health care and military biodefense. The present contribution describes a new versatile instrument and related procedures for array-based simultaneous detection of bacterial and plant toxins using a bioanalytical platform which combines the specificity of covalently immobilized capture probes with a dedicated instrumentation and immuno-based microarray analytics. The bioanalytical platform consists of a microstructured polymer slide serving both as support of printed arrays and as incubation chamber. The platform further includes an easy-to-operate instrument for simultaneous slide processing at selectable assay temperature. Cy5 coupled streptavidin is used as unifying fluorescent tracer. Fluorescence image analysis and signal quantitation allow determination of the toxin’s identity and concentration. The system’s performance has been investigated by immunological detection of Botulinum Neurotoxin type A (BoNT/A, Staphylococcal enterotoxin B (SEB, and the plant toxin ricin. Toxins were detectable at levels as low as 0.5–1 ng·mL−1 in buffer or in raw milk.

  2. A bioanalytical platform for simultaneous detection and quantification of biological toxins.

    Science.gov (United States)

    Weingart, Oliver G; Gao, Hui; Crevoisier, François; Heitger, Friedrich; Avondet, Marc-André; Sigrist, Hans

    2012-01-01

    Prevalent incidents support the notion that toxins, produced by bacteria, fungi, plants or animals are increasingly responsible for food poisoning or intoxication. Owing to their high toxicity some toxins are also regarded as potential biological warfare agents. Accordingly, control, detection and neutralization of toxic substances are a considerable economic burden to food safety, health care and military biodefense. The present contribution describes a new versatile instrument and related procedures for array-based simultaneous detection of bacterial and plant toxins using a bioanalytical platform which combines the specificity of covalently immobilized capture probes with a dedicated instrumentation and immuno-based microarray analytics. The bioanalytical platform consists of a microstructured polymer slide serving both as support of printed arrays and as incubation chamber. The platform further includes an easy-to-operate instrument for simultaneous slide processing at selectable assay temperature. Cy5 coupled streptavidin is used as unifying fluorescent tracer. Fluorescence image analysis and signal quantitation allow determination of the toxin's identity and concentration. The system's performance has been investigated by immunological detection of Botulinum Neurotoxin type A (BoNT/A), Staphylococcal enterotoxin B (SEB), and the plant toxin ricin. Toxins were detectable at levels as low as 0.5-1 ng · mL(-1) in buffer or in raw milk.

  3. Methods to validate the accuracy of an indirect calorimeter in the in-vitro setting.

    Science.gov (United States)

    Oshima, Taku; Ragusa, Marco; Graf, Séverine; Dupertuis, Yves Marc; Heidegger, Claudia-Paula; Pichard, Claude

    2017-12-01

    The international ICALIC initiative aims at developing a new indirect calorimeter according to the needs of the clinicians and researchers in the field of clinical nutrition and metabolism. The project initially focuses on validating the calorimeter for use in mechanically ventilated acutely ill adult patient. However, standard methods to validate the accuracy of calorimeters have not yet been established. This paper describes the procedures for the in-vitro tests to validate the accuracy of the new indirect calorimeter, and defines the ranges for the parameters to be evaluated in each test to optimize the validation for clinical and research calorimetry measurements. Two in-vitro tests have been defined to validate the accuracy of the gas analyzers and the overall function of the new calorimeter. 1) Gas composition analysis allows validating the accuracy of O 2 and CO 2 analyzers. Reference gas of known O 2 (or CO 2 ) concentration is diluted by pure nitrogen gas to achieve predefined O 2 (or CO 2 ) concentration, to be measured by the indirect calorimeter. O 2 and CO 2 concentrations to be tested were determined according to their expected ranges of concentrations during calorimetry measurements. 2) Gas exchange simulator analysis validates O 2 consumption (VO 2 ) and CO 2 production (VCO 2 ) measurements. CO 2 gas injection into artificial breath gas provided by the mechanical ventilator simulates VCO 2 . Resulting dilution of O 2 concentration in the expiratory air is analyzed by the calorimeter as VO 2 . CO 2 gas of identical concentration to the fraction of inspired O 2 (FiO 2 ) is used to simulate identical VO 2 and VCO 2 . Indirect calorimetry results from publications were analyzed to determine the VO 2 and VCO 2 values to be tested for the validation. O 2 concentration in respiratory air is highest at inspiration, and can decrease to 15% during expiration. CO 2 concentration can be as high as 5% in expired air. To validate analyzers for measurements of Fi

  4. Development and validation of a high-performance liquid chromatography-tandem mass spectrometry method for the simultaneous determination of irinotecan and its main metabolites in human plasma and its application in a clinical pharmacokinetic study.

    Directory of Open Access Journals (Sweden)

    Elena Marangon

    Full Text Available Irinotecan is currently used in several cancer regimens mainly in colorectal cancer (CRC. This drug has a narrow therapeutic range and treatment can lead to side effects, mainly neutropenia and diarrhea, frequently requiring discontinuing or lowering the drug dose. A wide inter-individual variability in irinotecan pharmacokinetic parameters and pharmacodynamics has been reported and associated to patients' genetic background. In particular, a polymorphism in the UGT1A1 gene (UGT1A1*28 has been linked to an impaired detoxification of SN-38 (irinotecan active metabolite to SN-38 glucuronide (SN-38G leading to increased toxicities. Therefore, therapeutic drug monitoring of irinotecan, SN-38 and SN-38G is recommended to personalize therapy. In order to quantify simultaneously irinotecan and its main metabolites in patients' plasma, we developed and validated a new, sensitive and specific HPLC-MS/MS method applicable to all irinotecan dosages used in clinic. This method required a small plasma volume, addition of camptothecin as internal standard and simple protein precipitation. Chromatographic separation was done on a Gemini C18 column (3 μM, 100 mm x 2.0 mm using 0.1% acetic acid/bidistilled water and 0.1% acetic acid/acetonitrile as mobile phases. The mass spectrometer worked with electrospray ionization in positive ion mode and selected reaction monitoring. The standard curves were linear (R2 ≥0.9962 over the concentration ranges (10-10000 ng/mL for irinotecan, 1-500 ng/mL for SN-38 and SN-38G and 1-5000 ng/mL for APC and had good back-calculated accuracy and precision. The intra- and inter-day precision and accuracy, determined on three quality control levels for all the analytes, were always <12.3% and between 89.4% and 113.0%, respectively. Moreover, we evaluated this bioanalytical method by re-analysis of incurred samples as an additional measure of assay reproducibility. This method was successfully applied to a pharmacokinetic study in

  5. NordVal: A Nordic system for validation of alternative microbiological methods

    DEFF Research Database (Denmark)

    Qvist, Sven

    2007-01-01

    NordVal was created in 1999 by the Nordic Committee of Senior Officials for Food Issues under the Nordic Council of Ministers. The Committee adopted the following objective for NordVal: NordVal evaluates the performance and field of application of alternative microbiological methods. This includes...... analyses of food, water, feed, animal faeces and food environmental samples in the Nordic countries. NordVal is managed by a steering group, which is appointed by the National Food Administrations in Denmark, Finland, Iceland, Norway and Sweden. The background for creation of NordVal was a Danish...... for obtaining a NordVal certificate. Details on the validation procedure can be found on the NordVal pages linked to the NMKL web site (www.nmkl.org). The acceptance of NordVal validated methods by the Nordic Food Administrations is strongly linked to a situation where the reliability of the alternative methods...

  6. A Validated, Rapid HPLC-ESI-MS/MS Method for the Determination of Lycopsamine.

    Science.gov (United States)

    Jedlinszki, Nikoletta; Csupor, Dezső

    2015-07-01

    The aim of the present work was to develop and validate an HPLC-MS/MS method for the determination of a major pyrrolizidine alkaloid of comfrey (lycopsamine) in aqueous samples as a basis for the development of a method for the determination of absorption of lycopsamine by human skin. A linear calibration curve was established in the range of 1.32-440 ng. The intraday precision during the 3-day validation period ranged between 0.57 and 2.48% while the interday precision was 1.70% and 1.95% for quality control samples. LOD was 0.014 ng and recovery was above 97%. The lycopsamine content of the samples stored for 9 and 25 days at 22 degrees C, 10 degrees C and -25 degrees C did not vary. These results underline the good repeatability and accuracy of our method and allow the analysis of samples with very low lycopsamine content.

  7. Validation of analytical methods for the stability studies of naproxen suppositories for infant and adult use

    International Nuclear Information System (INIS)

    Rodriguez Hernandez, Yaslenis; Suarez Perez, Yania; Garcia Pulpeiro, Oscar

    2011-01-01

    Analytical and validating studies were performed in this paper, with a view to using them in the stability studies of the future formulations of naproxen suppositories for children and adults. The most influential factors in the naproxen stability were determined, that is, the major degradation occurred in acid medium, oxidative medium and by light action. One high-performance liquid chromatography-based method was evaluated, which proved to be adequate to quantify naproxen in suppositories and was selective against degradation products. The quantification limit was 3,480 μg, so it was valid for these studies. Additionally, the parameters specificity for stability, detection and quantification limits were evaluated for the direct semi-aqueous acid-base method, which was formerly validated for the quality control and showed satisfactory results. Nevertheless, the volumetric methods were not regarded as stability indicators; therefore, this method will be used along with the chromatographic methods of choice, that is, thin-layer chromatography and highperformance liquid chromatography, to determine the degradation products

  8. Validation method for determination of cholesterol in human urine with electrochemical sensors using gold electrodes

    Science.gov (United States)

    Riyanto, Laksono, Tomy Agung

    2017-12-01

    Electrochemical sensors for the determination of cholesterol with Au as a working electrode (Au) and its application to the analysis of urine have been done. The gold electrode was prepared using gold pure (99.99%), with size 1.0 mm by length and wide respectively, connected with silver wire using silver conductive paint. Validation methods have been investigated in the analysis of cholesterol in human urine using electrochemical sensors or cyclic voltammetry (CV) method. The effect of electrolyte and uric acid concentration has been determined to produce the optimum method. Validation method parameters for cholesterol analysis in human urine using CV are precision, recovery, linearity, limit of detection (LOD) and limit of quantification (LOQ). The result showed the correlation of concentration of cholesterol to anodic peak current is the coefficient determination of R2 = 0.916. The results of the validation method showed the precision, recovery, linearity, LOD, and LOQ are 1.2539%, 144.33%, 0.916, 1.49 × 10-1 mM and 4.96 × 10-1 mM, respectively. As a conclusion is Au electrode is a good electrode for electrochemical sensors to determination of cholesterol in human urine.

  9. Determination of vitamin C in foods: current state of method validation.

    Science.gov (United States)

    Spínola, Vítor; Llorent-Martínez, Eulogio J; Castilho, Paula C

    2014-11-21

    Vitamin C is one of the most important vitamins, so reliable information about its content in foodstuffs is a concern to both consumers and quality control agencies. However, the heterogeneity of food matrixes and the potential degradation of this vitamin during its analysis create enormous challenges. This review addresses the development and validation of high-performance liquid chromatography methods for vitamin C analysis in food commodities, during the period 2000-2014. The main characteristics of vitamin C are mentioned, along with the strategies adopted by most authors during sample preparation (freezing and acidification) to avoid vitamin oxidation. After that, the advantages and handicaps of different analytical methods are discussed. Finally, the main aspects concerning method validation for vitamin C analysis are critically discussed. Parameters such as selectivity, linearity, limit of quantification, and accuracy were studied by most authors. Recovery experiments during accuracy evaluation were in general satisfactory, with usual values between 81 and 109%. However, few methods considered vitamin C stability during the analytical process, and the study of the precision was not always clear or complete. Potential future improvements regarding proper method validation are indicated to conclude this review. Copyright © 2014. Published by Elsevier B.V.

  10. Development and validation of a multiresidue method for pesticide analysis in honey by UFLC-MS

    Directory of Open Access Journals (Sweden)

    Adriana M. Zamudio S.

    2017-05-01

    Full Text Available A method for the determination of pesticide residues in honey by ultra fast liquid chromatography coupled with mass spectrometry was developed. For this purpose, different variations of the QuECHERS method were performed: (i amount of sample, (ii type of salt to control pH, (iii buffer pH, and (iv different mixtures for cleaning-up. In addition, to demonstrate that the method is reliable, different validation parameters were studied: accuracy, limits of detection and quantification, linearity and selectivity. The results showed that by means of the changes introduced it was possible to get a more selective method that improves the accuracy of about 19 pesticides selected from the original method. It was found that the method is suitable for the analysis of 50 pesticides, out of 56. Furthermore, with the developed method recoveries between 70 and 120% and relative standard deviation below 15% were found.

  11. Estimating Rooftop Suitability for PV: A Review of Methods, Patents, and Validation Techniques

    Energy Technology Data Exchange (ETDEWEB)

    Melius, J. [National Renewable Energy Lab. (NREL), Golden, CO (United States); Margolis, R. [National Renewable Energy Lab. (NREL), Golden, CO (United States); Ong, S. [National Renewable Energy Lab. (NREL), Golden, CO (United States)

    2013-12-01

    A number of methods have been developed using remote sensing data to estimate rooftop area suitable for the installation of photovoltaics (PV) at various geospatial resolutions. This report reviews the literature and patents on methods for estimating rooftop-area appropriate for PV, including constant-value methods, manual selection methods, and GIS-based methods. This report also presents NREL's proposed method for estimating suitable rooftop area for PV using Light Detection and Ranging (LiDAR) data in conjunction with a GIS model to predict areas with appropriate slope, orientation, and sunlight. NREL's method is validated against solar installation data from New Jersey, Colorado, and California to compare modeled results to actual on-the-ground measurements.

  12. Contribution to the validation of thermal ratchetting prevision methods in metallic structures; Contribution a la validation des methodes de prevision du rochet thermique dans les structures metalliques

    Energy Technology Data Exchange (ETDEWEB)

    Rakotovelo, A.M

    1998-03-01

    This work concerns the steady state assessment in the metallic structures subjected to thermomechanical cyclic loadings in biaxial stress state. The effect of the short time mechanical overloads is also investigated. The first chapter is devoted to a bibliographic research concerning the behaviour of the materials and the structures in the cyclic plasticity. Some works relate to the experimental aspect as well as the numerical one for the steady state assessment of such structures are presented. The experimental part of the study is presented in the second chapter. The experimental device was carried out in order to prescribe tension and torsion forces combined with cyclic thermal loading. Some tests was then carried out, among these tests certain include some overloads in tension or torsion. The last chapter describes the numerical calculations using different models (linear isotropic hardening, linear kinematic hardening and elasto-viscoplastic Chaboche's model) and the application of some simplified methods for the ratchetting assessment in the structures. We have considered two categories of methods. The first one is based on an elastic analysis (Bree's diagram, 3 Sm rule, efficiency rule) and the second one combines elastic analysis and elastoplastic analysis of the first cycle (Gatt's and Taleb's methods). The results of this study have enabled: to validate in the biaxial stress state an expression which takes into account the effect of mechanical short time overloads; to test the performances of considered models to describe the evolution of the structure during the first cycle and to take into account the effect of short time overloads. Among the considered models, the elastoplastic Chaboche's model seems to be the most accurate to describe the structure's behaviour during the first cycles; to validate some simplified methods. Certain methods based only on elastic analysis (Bee's diagram and efficiency rule) seem not

  13. Validity and feasibility of a digital diet estimation method for use with preschool children: a pilot study

    Science.gov (United States)

    The goal of the study was to assess the validity and feasibility of a digital diet estimation method for use with preschool children in Head Start. Preschool children and their caregivers participated in validation (n=22) and feasibility (n=24) pilot studies. Validity was determined in the metabolic...

  14. Validation of the chlorophyll fluorescence imaging method (CFI for early detection of herbicide resistance in weeds

    Directory of Open Access Journals (Sweden)

    Menegat, Alexander

    2014-02-01

    Full Text Available The increasing number of herbicide tolerant weed populations is illustrating the increasing demand for reliable methods for an accelerated detection of herbicide tolerance compared to greenhouse studies. Several methods for resistance quick detection have been published in previous years. One of the recent methods is the Chlorophyll Fluorescence Imaging Method (CFI. For this method changes in photosynthetic activity of the target organisms, caused by herbicides, are determined. General assumption of this method in terms of herbicide resistance detection is that each herbicidal compound, independent of the mode of action, will cause changes within the photosynthetic apparatus of the target organisms. This effect already could be confirmed for several modes of action (PSII, ALS, ACCase, EPSPS, synth. Auxins. Aim of this study is to validate this novel method on the basis of greenhouse experiments and single nucleotide polymorphisms (SNP analysis. The resistance profiles of 10 black-grass populations (Alopecurus myosuroides Huds. have been determined in greenhouse herbicide efficacy trials and constitutive SNP analyses of the survivors. With the CFI-method it was possible to detect the resistance profile as well as the resistance frequency within the populations. The results from the greenhouse experiments could be reproduced with conformity of 94%. This result is valid for the tested herbicides mesosulfuron, pyroxsulam as well as clodinafop and pinoxaden.

  15. Review on Laryngeal Palpation Methods in Muscle Tension Dysphonia: Validity and Reliability Issues.

    Science.gov (United States)

    Khoddami, Seyyedeh Maryam; Ansari, Noureddin Nakhostin; Jalaie, Shohreh

    2015-07-01

    Laryngeal palpation is a common clinical method for the assessment of neck and laryngeal muscles in muscle tension dysphonia (MTD). To review the available laryngeal palpation methods used in patients with MTD for the assessment, diagnosis, or document of treatment outcomes. A systematic review of the literature concerning palpatory methods in MTD was conducted using the databases MEDLINE (PubMed), ScienceDirect, Scopus, Web of science, Web of knowledge and Cochrane Library between July and October 2013. Relevant studies were identified by one reviewer based on screened titles/abstracts and full texts. Manual searching was also used to track the source literature. There were five main as well as miscellaneous palpation methods that were different according to target anatomical structures, judgment or grading system, and using tasks. There were only a few scales available, and the majority of the palpatory methods were qualitative. Most of the palpatory methods evaluate the tension at both static and dynamic tasks. There was little information about the validity and reliability of the available methods. The literature on the scientific evidence of muscle tension indicators perceived by laryngeal palpation in MTD is scarce. Future studies should be conducted to investigate the validity and reliability of palpation methods. Copyright © 2015 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

  16. Validity Evaluation of the Assessment Method for Postural Loading on the Upper Body in Printing Industry

    Directory of Open Access Journals (Sweden)

    Mohammad Khandan

    2016-07-01

    Full Text Available Background and Objectives: Musculoskeletal disorders and injuries are known as a global occupational challenge. These injuries are more are concentrated in the upper limb. There are several methods to assess this kind of disorders, each of which have different efficiencies for various jobs based on their strengths and weaknesses. This study aimed to assess the validity of LUBA method in order to evaluate risk factors for musculoskeletal disorders in a printing industry in Qom province, 2014. Methods: In this descriptive cross-sectional study, all operational workers (n=94 were investigated in 2014. Nordic Musculoskeletal Questionnaire (NMQ was used to collect data on musculoskeletal disorders. We also used LUBA method to analyze postures in four different parts of the body (neck, shoulder, elbow, and wrist. The obtained data were analyzed using Mann-Whitney, Kruskal Wallis, and Kappa agreement tests. Results: Lumbar region of back with 35.1% prevalence had the most problems. The results of LUBA method showed that most postures were located at the second corrective action level, and need further studies. Agreement between assessment of shoulder posture and its disorders was significant (p0.05.  Conclusion: According to the results of this study on reliability and predictive validity of the LUBA method in printing industry, it can be concluded that this method is not a reliable method for posture assessment; however, further and more comprehensive studies are recommended.  

  17. Submission of scientifically sound and ethical manuscripts to peer-reviewed journals - a reviewer's personal perspective on bioanalytical publications.

    Science.gov (United States)

    Weng, Naidong

    2012-11-01

    In the pharmaceutical industry, bioanalysis is very dynamic and is probably one of the few fields of research covering the entire drug discovery, development and post-marketing process. Important decisions on drug safety can partially rely on bioanalytical data, which therefore can be subject to regulatory scrutiny. Bioanalytical scientists have historically contributed significant numbers of scientific manuscripts in many peer-reviewed analytical journals. All of these journals provide some high-level instructions, but they also leave sufficient flexibility for reviewers to perform independent critique and offer recommendations for each submitted manuscript. Reviewers play a pivotal role in the process of bioanalytical publication to ensure the publication of high-quality manuscripts in a timely fashion. Their efforts usually lead to improved manuscripts. However, it has to be a joint effort among authors, reviewers and editors to promote scientifically sound and ethically fair bioanalytical publications. Most of the submitted manuscripts were well written with only minor or moderate revisions required for further improvement. Nevertheless, there were small numbers of submitted manuscripts that did not meet the requirements for publications because of scientific or ethical deficiencies, which are discussed in this Letter to the Editor. Copyright © 2012 John Wiley & Sons, Ltd.

  18. Validation of the Standard Method for Assessing Flicker From Wind Turbines

    DEFF Research Database (Denmark)

    Barahona Garzon, Braulio; Sørensen, Poul Ejnar; Christensen, L.

    2011-01-01

    This paper studies the validity of the standard method in IEC 61400-21 for assessing the flicker emission from multiple wind turbines. The standard method is based on testing a single wind turbine and then using the results of this test to assess the flicker emission from a number of wind turbines...... the flicker emission at the collection line; this assessment is then compared to the actual measurements in order to study the accuracy of the estimation. It was observed in both wind farms, that the assessment based on the standard method is statistically conservative compared to the measurements. The reason...... for this is the statistical characteristics of flicker emission....

  19. A method of knowledge base verification and validation for nuclear power plants expert systems

    International Nuclear Information System (INIS)

    Kwon, Il Won

    1996-02-01

    The adoption of expert systems mainly as operator supporting systems is becoming increasingly popular as the control algorithms of system become more and more sophisticated and complicated. As a result of this popularity, a large number of expert systems are developed. The nature of expert systems, however, requires that they be verified and validated carefully and that detailed methodologies for their development be devised. Therefore, it is widely noted that assuring the reliability of expert systems is very important, especially in nuclear industry, and it is also recognized that the process of verification and validation is an essential part of reliability assurance for these systems. Research and practices have produced numerous methods for expert system verification and validation (V and V) that suggest traditional software and system approaches to V and V. However, many approaches and methods for expert system V and V are partial, unreliable, and not uniform. The purpose of this paper is to present a new approach to expert system V and V, based on Petri nets, providing a uniform model. We devise and suggest an automated tool, called COKEP (Checker Of Knowledge base using Extended Petri net), for checking incorrectness, inconsistency, and incompleteness in a knowledge base. We also suggest heuristic analysis for validation process to show that the reasoning path is correct

  20. Overview of US efforts to validate analysis methods and design criteria

    International Nuclear Information System (INIS)

    Corum, J.M.

    1979-01-01

    As a part of its basic breeder reactor technology activities, the United States has a High-Temperature Structural Design Program aimed at establishing, and transferring to designers a rationally sound and experimentally validated structural design technology that will assure freedom from structural failures. Both development and validation efforts are centered on three main ingredients of the technology: (1) mathematical descriptions (constitutive equations) of the deformation behavior of the alloys of interest, (2) time-dependent rupture, or cracking, models, again for the alloys of interest, and (3) detailed design analysis methods and failure criteria based on these inputs. The objective of this presentation is to provide a brief overview of the status of efforts to experimentally assess and validate each of these three technology ingredients. In the case of deformation and rupture models, the current procedures and rules are outlined, and their significant features are assessed through comparisons with results from uniaxial and multiaxial material behavior tests. Design analysis methods and failure criteria are, on the other hand, discussed relative to the results of experimental benchmark structural tests. Although several significant needs and problem areas remain, data generated to date tend to provide limited validation of key aspects of the existing technology. Current constitutive equations represent many of the observed behavioral features; limited available data support current time-dependent rupture criteria reasonably well; and it is observed that structural analysis predictions capture most of the experimentally observed features of inelastic structural behavior

  1. Nucleic acid and peptide aptamers: fundamentals and bioanalytical aspects.

    Science.gov (United States)

    Mascini, Marco; Palchetti, Ilaria; Tombelli, Sara

    2012-02-06

    In recent years new nucleic acid and protein-based combinatorial molecules have attracted the attention of researchers working in various areas of science, ranging from medicine to analytical chemistry. These molecules, called aptamers, have been proposed as alternatives to antibodies in many different applications. The aim of this Review is to illustrate the peculiarities of these combinatorial molecules which have initially been explored for their importance in molecular medicine, but have enormous potential in other biotechnological fields historically dominated by antibodies, such as bioassays. A description of these molecules is given, and the methods for their selection and production are also summarized. Moreover, critical aspects related to these molecules are discussed. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. Validation of MR thermometry: method for temperature probe sensor registration accuracy in head and neck phantoms.

    Science.gov (United States)

    Tarasek, Matthew R; Pellicer, Ruben; Hofstetter, Lorne W; Numan, Wouter C M; Bakker, Jurriaan F; Kotek, Gyula; Togni, Paolo; Verhaart, René F; Fiveland, Eric W; Houston, Gavin C; van Rhoon, Gerard C; Paulides, Margarethus Marius; Yeo, Desmond Teck Beng

    2014-03-01

    Magnetic resonance thermometry (MRT) is an attractive means to non-invasively monitor in vivo temperature during head and neck hyperthermia treatments because it can provide multi-dimensional temperature information with high spatial resolution over large regions of interest. However, validation of MRT measurements in a head and neck clinical set-up is crucial to ensure the temperature maps are accurate. Here we demonstrate a unique approach for temperature probe sensor localisation in head and neck hyperthermia test phantoms. We characterise the proton resonance frequency shift temperature coefficient and validate MRT measurements in an oil-gel phantom by applying a combination of MR imaging and 3D spline fitting for accurate probe localisation. We also investigate how uncertainties in both the probe localisation and the proton resonance frequency shift (PRFS) thermal coefficient affect the registration of fibre-optic reference temperature probe and MRT readings. The method provides a two-fold advantage of sensor localisation and PRFS thermal coefficient calibration. We provide experimental data for two distinct head and neck phantoms showing the significance of this method as it mitigates temperature probe localisation errors and thereby increases accuracy of MRT validation results. The techniques presented here may be used to simplify calibration experiments that use an interstitial heating device, or any heating method that provides rapid and spatially localised heat distributions. Overall, the experimental verification of the data registration and PRFS thermal coefficient calibration technique provides a useful benchmarking method to maximise MRT accuracy in any similar context.

  3. Development and validation of a reversed phase liquid chromatographic method for analysis of griseofulvin and impurities.

    Science.gov (United States)

    Kahsay, Getu; Adegoke, Aremu Olajire; Van Schepdael, Ann; Adams, Erwin

    2013-06-01

    A simple and robust reversed phase liquid chromatographic method was developed and validated for the quantitative determination of griseofulvin (GF) and its impurities in drug substances and drug products (tablets). Chromatographic separation was achieved on a Discovery C18 (250mm×4.6mm, 5μm) column kept at 30°C. The mobile phase consisted of a gradient mixture of mobile phase A (water-0.1% formic acid pH 4.5, 80:20, v/v) and B (ACN-water-0.1% formic acid pH 4.5, 65:15:20, v/v/v) pumped at a flow rate of 1.0mL/min. UV detection was performed at 290nm. The method was validated for its robustness, sensitivity, precision, accuracy and linearity based on ICH guidelines. The robustness study was performed by means of an experimental design and multivariate analysis. Satisfactory results were obtained from the validation studies. The use of volatile mobile phases allowed for the identification of three main impurities present above the identification threshold using mass spectrometry (MS). The developed LC method has been applied for the assay and impurity determination of GF drug substances and tablets. The method could be very useful for the quality control of GF and its impurities in bulk and formulated dosage forms. Copyright © 2013 Elsevier B.V. All rights reserved.

  4. Validation of a New Placebo Interferential Current Method: A New Placebo Method of Electrostimulation.

    Science.gov (United States)

    Mendonça Araújo, Fernanda; Alves Menezes, Mayara; Martins de Araújo, Ariane; Abner Dos Santos Sousa, Thiago; Vasconcelos Lima, Lucas; Ádan Nunes Carvalho, Elyson; Melo DeSantana, Josimari

    2017-01-01

    The present study aimed to investigate if a new placebo device for interferential current (IFC) that delivers current during only the first 40 seconds of stimulation is effective at promoting adequate subject blinding. Seventy-five subjects were recruited and enrolled into three groups: active IFC, inactive placebo, and new placebo. Pressure pain threshold (PPT), cutaneous sensory threshold (CST), and pain intensity were measured before and after the intervention. After the final assessment, the subjects and the investigator who applied the current were asked about the type of stimulation administered. None of the placebo forms studied resulted in significant changes to PPT, CST, or pain intensity. The subjects stimulated with active IFC at high intensities (> 17 mA) of stimulation showed higher PPT and CST and lower pain intensity than subjects stimulated at low intensities ( p < 0.03). The new placebo method blinded the investigator in 100% of cases of IFC and 60% of subjects stimulated, whereas for inactive placebo, the investigator was blinded at a rate of 0% and 34% of subjects. The new method of placebo IFC was effective for blinding of research investigators and most of the active IFC-treated subjects, promoting an appropriate placebo method. © 2016 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

  5. Experimental validation of the buildings energy performance (PEC assessment methods with reference to occupied spaces heating

    Directory of Open Access Journals (Sweden)

    Cristian PETCU

    2010-01-01

    Full Text Available This paper is part of the series of pre-standardization research aimed to analyze the existing methods of calculating the Buildings Energy Performance (PEC in view of their correction of completing. The entire research activity aims to experimentally validate the PEC Calculation Algorithm as well as the comparative application, on the support of several case studies focused on representative buildings of the stock of buildings in Romania, of the PEC calculation methodology for buildings equipped with occupied spaces heating systems. The targets of the report are the experimental testing of the calculation models so far known (NP 048-2000, Mc 001-2006, SR EN 13790:2009, on the support provided by the CE INCERC Bucharest experimental building, together with the complex calculation algorithms specific to the dynamic modeling, for the evaluation of the occupied spaces heat demand in the cold season, specific to the traditional buildings and to modern buildings equipped with solar radiation passive systems, of the ventilated solar space type. The schedule of the measurements performed in the 2008-2009 cold season is presented as well as the primary processing of the measured data and the experimental validation of the heat demand monthly calculation methods, on the support of CE INCERC Bucharest. The calculation error per heating season (153 days of measurements between the measured heat demand and the calculated one was of 0.61%, an exceptional value confirming the phenomenological nature of the INCERC method, NP 048-2006. The mathematical model specific to the hourly thermal balance is recurrent – decisional with alternating paces. The experimental validation of the theoretical model is based on the measurements performed on the CE INCERC Bucharest building, within a time lag of 57 days (06.01-04.03.2009. The measurements performed on the CE INCERC Bucharest building confirm the accuracy of the hourly calculation model by comparison to the values

  6. Validation of Cyanoacrylate Method for Collection of Stratum Corneum in Human Skin for Lipid Analysis

    DEFF Research Database (Denmark)

    Jungersted, JM; Hellgren, Lars; Drachmann, Tue

    2010-01-01

    Background and Objective: Lipids in the stratum corneum (SC) are of major importance for the skin barrier function. Many different methods have been used for the collection of SC for the analysis of SC lipids. The objective of the present study was to validate the cyanoacrylate method for the col......Background and Objective: Lipids in the stratum corneum (SC) are of major importance for the skin barrier function. Many different methods have been used for the collection of SC for the analysis of SC lipids. The objective of the present study was to validate the cyanoacrylate method...... for the collection of SC in relation to lipid analysis. Methods: The results of the lipid analysis (ceramide/cholesterol and ceramide profile) of SC samples obtained by the cyanoacrylate method were compared to the results of the lipid analysis of mechanically removed SC samples. The intra- and interindividual...... variations in lipid composition were assessed when using the cyanoacrylate method, and lipid compositions in cyanoacrylate samples and samples taken from different depths of SC were compared. Results: No statistically significant differences were found between mean values of lipids from the mechanically...

  7. In Vitro Dissolution Profile of Dapagliflozin: Development, Method Validation, and Analysis of Commercial Tablets

    Directory of Open Access Journals (Sweden)

    Rafaela Zielinski Cavalheiro de Meira

    2017-01-01

    Full Text Available Dapagliflozin was the first of its class (inhibitors of sodium-glucose cotransporter to be approved in Europe, USA, and Brazil. As the drug was recently approved, there is the need for research on analytical methods, including dissolution studies for the quality evaluation and assurance of tablets. The dissolution methodology was developed with apparatus II (paddle in 900 mL of medium (simulated gastric fluid, pH 1.2, temperature set at 37±0.5°C, and stirring speed of 50 rpm. For the quantification, a spectrophotometric (λ=224 nm method was developed and validated. In validation studies, the method proved to be specific and linear in the range from 0.5 to 15 μg·mL−1 (r2=0.998. The precision showed results with RSD values lower than 2%. The recovery of 80.72, 98.47, and 119.41% proved the accuracy of the method. Through a systematic approach by applying Factorial 23, the robustness of the method was confirmed (p>0.05. The studies of commercial tablets containing 5 or 10 mg demonstrated that they could be considered similar through f1, f2, and dissolution efficiency analyses. Also, the developed method can be used for the quality evaluation of dapagliflozin tablets and can be considered as a scientific basis for future official pharmacopoeial methods.

  8. Development and Validation of HPLC-PDA Assay method of Frangula emodin

    Directory of Open Access Journals (Sweden)

    Deborah Duca

    2016-03-01

    Full Text Available Frangula emodin, (1,3,8-trihydroxy-6-methyl-anthraquinone, is one of the anthraquinone derivatives found abundantly in the roots and bark of a number of plant families traditionally used to treat constipation and haemorrhoids. The present study describes the development and subsequent validation of a specific Assay HPLC method for emodin. The separation was achieved on a Waters Symmetry C18, 4.6 × 250 mm, 5 μm particle size, column at a temperature of 35 °C, with UV detection at 287 and 436 nm. An isocratic elution mode consisting of 0.1% formic acid and 0.01% trifluoroacetic acid as the aqueous mobile phase, and methanol was used. The method was successfully and statistically validated for linearity, range, precision, accuracy, specificity and solution stability.

  9. RETROSPECTIVE METHOD VALIDATION AND UNCERTAINTY ESTIMATION FOR ACTINIDES DETERMINATION IN EXCRETA BY ALPHA SPECTROMETRY.

    Science.gov (United States)

    Hernández, C; Sierra, I

    2016-09-01

    Two essential technical requirements of ISO 17025 guide for accreditation of testing and calibration laboratories are the validation of methods and the estimation of all sources of uncertainty that may affect the analytical result. Bioelimination Laboratory from Radiation Dosimetry Service of CIEMAT (Spain) uses alpha spectrometry to quantify alpha emitters (Pu, Am, Th, U and Cm isotopes) in urine and faecal samples from workers exposed to internal radiation. Therefore and as a step previous to achieving the ISO 17025 accreditation, the laboratory has performed retrospective studies based on the obtained results in the past few years to validate the analytical method. Uncertainty estimation was done identifying and quantifying all the contributions, and finally the overall combined standard uncertainty was calculated. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  10. Validation of cleaning method for various parts fabricated at a Beryllium facility

    Energy Technology Data Exchange (ETDEWEB)

    Davis, Cynthia M. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2015-12-15

    This study evaluated and documented a cleaning process that is used to clean parts that are fabricated at a beryllium facility at Los Alamos National Laboratory. The purpose of evaluating this cleaning process was to validate and approve it for future use to assure beryllium surface levels are below the Department of Energy’s release limits without the need to sample all parts leaving the facility. Inhaling or coming in contact with beryllium can cause an immune response that can result in an individual becoming sensitized to beryllium, which can then lead to a disease of the lungs called chronic beryllium disease, and possibly lung cancer. Thirty aluminum and thirty stainless steel parts were fabricated on a lathe in the beryllium facility, as well as thirty-two beryllium parts, for the purpose of testing a parts cleaning method that involved the use of ultrasonic cleaners. A cleaning method was created, documented, validated, and approved, to reduce beryllium contamination.

  11. Software phantom with realistic speckle modeling for validation of image analysis methods in echocardiography

    Science.gov (United States)

    Law, Yuen C.; Tenbrinck, Daniel; Jiang, Xiaoyi; Kuhlen, Torsten

    2014-03-01

    Computer-assisted processing and interpretation of medical ultrasound images is one of the most challenging tasks within image analysis. Physical phenomena in ultrasonographic images, e.g., the characteristic speckle noise and shadowing effects, make the majority of standard methods from image analysis non optimal. Furthermore, validation of adapted computer vision methods proves to be difficult due to missing ground truth information. There is no widely accepted software phantom in the community and existing software phantoms are not exible enough to support the use of specific speckle models for different tissue types, e.g., muscle and fat tissue. In this work we propose an anatomical software phantom with a realistic speckle pattern simulation to _ll this gap and provide a exible tool for validation purposes in medical ultrasound image analysis. We discuss the generation of speckle patterns and perform statistical analysis of the simulated textures to obtain quantitative measures of the realism and accuracy regarding the resulting textures.

  12. Development and validation of the discriminating method of prasugrel dissolution in tablets using ultraviolet detection

    Directory of Open Access Journals (Sweden)

    Camila Rigobello

    2014-10-01

    Full Text Available Current study develops and validates a dissolution test for Prasugrel hydrochloride 10 mg in coated tablets. After sink condition, filters and drug stability were evaluated, the discriminatory dissolution conditions were achieved with a USP apparatus 1 (basket at 50 rpm stirring speed and 900 mL of 0.01 M HCl as dissolution medium. The UV spectrometric method at 220 nm was performed and validated for the determination of Prasugrel. The parameters specificity, linearity, accuracy, precision and robustness were evaluated according to international protocols. UV method and dissolution test proposed in current analysis may be applied for quality control of coated tablets containing Prasugrel since there is no official monograph for this drug.

  13. Method of administration of PROMIS scales did not significantly impact score level, reliability, or validity

    DEFF Research Database (Denmark)

    Bjorner, Jakob B; Rose, Matthias; Gandek, Barbara

    2014-01-01

    OBJECTIVES: To test the impact of the method of administration (MOA) on score level, reliability, and validity of scales developed in the Patient Reported Outcomes Measurement Information System (PROMIS). STUDY DESIGN AND SETTING: Two nonoverlapping parallel forms each containing eight items from...... questionnaire (PQ), personal digital assistant (PDA), or personal computer (PC) and a second form by PC, in the same administration. Method equivalence was evaluated through analyses of difference scores, intraclass correlations (ICCs), and convergent/discriminant validity. RESULTS: In difference score analyses...... showed no differential effect by MOA. Participants preferred screen interface over PQ and IVR. CONCLUSION: We found no statistically or clinically significant differences in score levels or psychometric properties of IVR, PQ, or PDA administration compared with PC....

  14. [Validation Study for Analytical Method of Diarrhetic Shellfish Poisons in 9 Kinds of Shellfish].

    Science.gov (United States)

    Yamaguchi, Mizuka; Yamaguchi, Takahiro; Kakimoto, Kensaku; Nagayoshi, Haruna; Okihashi, Masahiro; Kajimura, Keiji

    2016-01-01

    A method was developed for the simultaneous determination of okadaic acid, dinophysistoxin-1 and dinophysistoxin-2 in shellfish using ultra performance liquid chromatography with tandem mass spectrometry. Shellfish poisons in spiked samples were extracted with methanol and 90% methanol, and were hydrolyzed with 2.5 mol/L sodium hydroxide solution. Purification was done on an HLB solid-phase extraction column. This method was validated in accordance with the notification of Ministry of Health, Labour and Welfare of Japan. As a result of the validation study in nine kinds of shellfish, the trueness, repeatability and within-laboratory reproducibility were 79-101%, less than 12 and 16%, respectively. The trueness and precision met the target values of notification.

  15. Establishing survey validity and reliability for American Indians through "think aloud" and test-retest methods.

    Science.gov (United States)

    Hauge, Cindy Horst; Jacobs-Knight, Jacque; Jensen, Jamie L; Burgess, Katherine M; Puumala, Susan E; Wilton, Georgiana; Hanson, Jessica D

    2015-06-01

    The purpose of this study was to use a mixed-methods approach to determine the validity and reliability of measurements used within an alcohol-exposed pregnancy prevention program for American Indian women. To develop validity, content experts provided input into the survey measures, and a "think aloud" methodology was conducted with 23 American Indian women. After revising the measurements based on this input, a test-retest was conducted with 79 American Indian women who were randomized to complete either the original measurements or the new, modified measurements. The test-retest revealed that some of the questions performed better for the modified version, whereas others appeared to be more reliable for the original version. The mixed-methods approach was a useful methodology for gathering feedback on survey measurements from American Indian participants and in indicating specific survey questions that needed to be modified for this population. © The Author(s) 2015.

  16. Validation of analysis methods for assessing flawed piping subjected to dynamic loading

    Energy Technology Data Exchange (ETDEWEB)

    Olson, R.J.; Wolterman, R.L.; Wilkowski, G.M. [Battelle, Columbus, OH (United States); Kot, C.A. [Argonne National Lab., IL (United States)

    1994-08-01

    Argonne National Laboratory and Battelle have jointly conducted a research program for the USNRC to evaluate the ability of current engineering analysis methods and one state-of-the-art analysis method to predict the behavior of circumferentially surface-cracked pipe system water-hammer experiment. The experimental data used in the evaluation were from the HDR Test Group E31 series conducted by the Kernforschungszentrum Karlsruhe (KfK) in Germany. The incentive for this evaluation was that simplified engineering methods, as well as newer ``state-of-the-art`` fracture analysis methods, have been typically validated only with static experimental data. Hence, these dynamic experiments were of high interest. High-rate dynamic loading can be classified as either repeating, e.g., seismic, or nonrepeating, e.g., water hammer. Development of experimental data and validation of cracked pipe analyses under seismic loading (repeating dynamic loads) are being pursued separately within the NRC`s International Piping Integrity Research Group (IPIRG) program. This report describes developmental and validation efforts to predict crack stability under water hammer loading, as well as comparisons using currently used analysis procedures. Current fracture analysis methods use the elastic stress analysis loads decoupled from the fracture mechanics analysis, while state-of-the-art methods employ nonlinear cracked-pipe time-history finite element analyses. The results showed that the current decoupled methods were conservative in their predictions, whereas the cracked pipe finite element analyses were more accurate, yet slightly conservative. The nonlinear time-history cracked-pipe finite element analyses conducted in this program were also attractive in that they were done on a small Apollo DN5500 workstation, whereas other cracked-pipe dynamic analyses conducted in Europe on the same experiments required the use of a CRAY2 supercomputer, and were less accurate.

  17. Potential of accuracy profile for method validation in inductively coupled plasma spectrochemistry

    International Nuclear Information System (INIS)

    Mermet, J.M.; Granier, G.

    2012-01-01

    Method validation is usually performed over a range of concentrations for which analytical criteria must be verified. One important criterion in quantitative analysis is accuracy, i.e. the contribution of both trueness and precision. The study of accuracy over this range is called an accuracy profile and provides experimental tolerance intervals. Comparison with acceptability limits fixed by the end user defines a validity domain. This work describes the computation involved in the building of the tolerance intervals, particularly for the intermediate precision with within-laboratory experiments and for the reproducibility with interlaboratory studies. Computation is based on ISO 5725‐4 and on previously published work. Moreover, the bias uncertainty is also computed to verify the bias contribution to accuracy. The various types of accuracy profile behavior are exemplified with results obtained by using ICP-MS and ICP-AES. This procedure allows the analyst to define unambiguously a validity domain for a given accuracy. However, because the experiments are time-consuming, the accuracy profile method is mainly dedicated to method validation. - Highlights: ► An analytical method is defined by its accuracy, i.e. both trueness and precision. ► The accuracy as a function of an analyte concentration is an accuracy profile. ► Profile basic concepts are explained for trueness and intermediate precision. ► Profile-based tolerance intervals have to be compared with acceptability limits. ► Typical accuracy profiles are given for both ICP-AES and ICP-MS techniques.

  18. Validation of the analytical method for sodium dichloroisocyanurate aimed at drinking water disinfection

    International Nuclear Information System (INIS)

    Martinez Alvarez, Luis Octavio; Alejo Cisneros, Pedro; Garcia Pereira, Reynaldo; Campos Valdez, Doraily

    2014-01-01

    Cuba has developed the first effervescent 3.5 mg sodium dichloroisocyanurate tablets as a non-therapeutic active principle. This ingredient releases certain amount of chlorine when dissolved into a litre of water and it can cause adequate disinfection of drinking water ready to be taken after 30 min. Developing and validating an analytical iodometric method applicable to the quality control of effervescent 3.5 mg sodium dichloroisocyanurate tablets

  19. Validation of the material point method and plasticity with Taylor impact tests

    OpenAIRE

    Banerjee, Biswajit

    2012-01-01

    Taylor impacts tests were originally devised to determine the dynamic yield strength of materials at moderate strain rates. More recently, such tests have been used extensively to validate numerical codes for the simulation of plastic deformation. In this work, we use the material point method to simulate a number of Taylor impact tests to compare different Johnson-Cook, Mechanical Threshold Stress, and Steinberg-Guinan-Cochran plasticity models and the vob Mises and Gurson-Tvergaard-Needlema...

  20. Development and Validation of a Stability-Indicating LC-UV Method ...

    African Journals Online (AJOL)

    Development and Validation of a Stability-Indicating LC-UV Method for Simultaneous Determination of Ketotifen and Cetirizine in Pharmaceutical Dosage Forms. ... 5 μm) using an isocratic mobile phase that consisted of acetonitrile and 10 mM disodium hydrogen phosphate buffer (pH 6.5) in a ratio of 45:55 % v/v at a flow ...

  1. Validation and Verification (V and V) Testing on Midscale Flame Resistant (FR) Test Method

    Science.gov (United States)

    2016-12-16

    person shall be subject to any penalty for failing to comply with a collection of information if it does not display a currently valid OMB control ...roughly equally over the body surface, excluding the hands and feet. The F1930 test method requires a minimum of 100 sensors [1]. If copper slug ...copper slug . In fact, though a large number of sensors is employed, a comparison with the total sensor area with typical numbers for body surface area

  2. New clinical validation method for automated sphygmomanometer: a proposal by Japan ISO-WG for sphygmomanometer standard.

    Science.gov (United States)

    Shirasaki, Osamu; Asou, Yosuke; Takahashi, Yukio

    2007-12-01

    Owing to fast or stepwise cuff deflation, or measuring at places other than the upper arm, the clinical accuracy of most recent automated sphygmomanometers (auto-BPMs) cannot be validated by one-arm simultaneous comparison, which would be the only accurate validation method based on auscultation. Two main alternative methods are provided by current standards, that is, two-arm simultaneous comparison (method 1) and one-arm sequential comparison (method 2); however, the accuracy of these validation methods might not be sufficient to compensate for the suspicious accuracy in lateral blood pressure (BP) differences (LD) and/or BP variations (BPV) between the device and reference readings. Thus, the Japan ISO-WG for sphygmomanometer standards has been studying a new method that might improve validation accuracy (method 3). The purpose of this study is to determine the appropriateness of method 3 by comparing immunity to LD and BPV with those of the current validation methods (methods 1 and 2). The validation accuracy of the above three methods was assessed in human participants [N=120, 45+/-15.3 years (mean+/-SD)]. An oscillometric automated monitor, Omron HEM-762, was used as the tested device. When compared with the others, methods 1 and 3 showed a smaller intra-individual standard deviation of device error (SD1), suggesting their higher reproducibility of validation. The SD1 by method 2 (P=0.004) significantly correlated with the participant's BP, supporting our hypothesis that the increased SD of device error by method 2 is at least partially caused by essential BPV. Method 3 showed a significantly (P=0.0044) smaller interparticipant SD of device error (SD2), suggesting its higher interparticipant consistency of validation. Among the methods of validation of the clinical accuracy of auto-BPMs, method 3, which showed the highest reproducibility and highest interparticipant consistency, can be proposed as being the most appropriate.

  3. Bioanalytical Applications of Real-Time ATP Imaging Via Bioluminescence

    Energy Technology Data Exchange (ETDEWEB)

    Gruenhagen, Jason Alan [Iowa State Univ., Ames, IA (United States)

    2003-01-01

    The research discussed within involves the development of novel applications of real-time imaging of adenosine 5'-triphosphate (ATP). ATP was detected via bioluminescence and the firefly luciferase-catalyzed reaction of ATP and luciferin. The use of a microscope and an imaging detector allowed for spatially resolved quantitation of ATP release. Employing this method, applications in both biological and chemical systems were developed. First, the mechanism by which the compound 48/80 induces release of ATP from human umbilical vein endothelial cells (HUVECs) was investigated. Numerous enzyme activators and inhibitors were utilized to probe the second messenger systems involved in release. Compound 48/80 activated a G{sub q}-type protein to initiate ATP release from HUVECs. Ca2+ imaging along with ATP imaging revealed that activation of phospholipase C and induction of intracellular Ca2+ signaling were necessary for release of ATP. Furthermore, activation of protein kinase C inhibited the activity of phospholipase C and thus decreased the magnitude of ATP release. This novel release mechanism was compared to the existing theories of extracellular release of ATP. Bioluminescence imaging was also employed to examine the role of ATP in the field of neuroscience. The central nervous system (CNS) was dissected from the freshwater snail Lymnaea stagnalis. Electrophysiological experiments demonstrated that the neurons of the Lymnaea were not damaged by any of the components of the imaging solution. ATP was continuously released by the ganglia of the CNS for over eight hours and varied from ganglion to ganglion and within individual ganglia. Addition of the neurotransmitters K+ and serotonin increased release of ATP in certain regions of the Lymnaea CNS. Finally, the ATP imaging technique was investigated for the study of drug release systems. MCM-41-type mesoporous nanospheres were loaded with ATP and end-capped with mercaptoethanol

  4. Development and validation of a novel method for evaluating behavior and temperament in guide dogs.

    Science.gov (United States)

    Serpell, J A.; Hsu, Y

    2001-06-01

    Most guide and service dog organizations would benefit from the development of accurate methods for the early evaluation of canine temperament traits. This paper describes the development and validation of a novel questionnaire method for assessing behavior and temperament in 1-year-old guide dogs. Volunteer puppy-raisers scored a total of 1097 prospective guide dogs on a series of 40 semantic differential-type, behavioral rating scales. Principle components factor analysis of these scores extracted eight stable and interpretable common factors: stranger-directed fear/aggression, non-social fear, energy level, owner-directed aggression, chasing, trainability, attachment, and dog-directed fear/aggression. Three of these eight factors exhibited moderate internal consistency (Cronbach's alpha>/=0.72), while the reliabilities of the remaining factors were relatively low (Cronbach's alpha=0.53-0.61). The eight factors were then validated against the guide dog school's own criteria for rejecting dogs for behavioral reasons. The results of this analysis confirmed the construct validity of the puppy raisers' questionnaire assessments of their dogs, and suggested that such methods can provide a useful and accurate means of predicting the suitability of dogs for guiding work. Various modifications to the original questionnaire are proposed in order to enhance its overall reliability.

  5. Bridging the Gap Between Validation and Implementation of Non-Animal Veterinary Vaccine Potency Testing Methods

    Directory of Open Access Journals (Sweden)

    Alistair Currie

    2011-11-01

    Full Text Available In recent years, technologically advanced high-throughput techniques have been developed that replace, reduce or refine animal use in vaccine quality control tests. Following validation, these tests are slowly being accepted for use by international regulatory authorities. Because regulatory acceptance itself has not guaranteed that approved humane methods are adopted by manufacturers, various organizations have sought to foster the preferential use of validated non-animal methods by interfacing with industry and regulatory authorities. After noticing this gap between regulation and uptake by industry, we began developing a paradigm that seeks to narrow the gap and quicken implementation of new replacement, refinement or reduction guidance. A systematic analysis of our experience in promoting the transparent implementation of validated non-animal vaccine potency assays has led to the refinement of our paradigmatic process, presented here, by which interested parties can assess the local regulatory acceptance of methods that reduce animal use and integrate them into quality control testing protocols, or ensure the elimination of peripheral barriers to their use, particularly for potency and other tests carried out on production batches.

  6. Experimental validation of numerical simulations: a comparison of computational fluid dynamics and the oil film method.

    Science.gov (United States)

    Stoiber, M; Grasl, C; Pirker, S; Huber, L; Gittler, P; Schima, H

    2007-04-01

    Today Computational Fluid Dynamics (CFD) is used for simulating flow in many applications. The quality of the results, however, depends on various factors, like grid quality, boundary conditions and the computational model of the fluid. For this reason, it is important to validate the performed computation with experimental results. In this work, a comparison of numerical simulation with the oil film method was performed for two cardiovascular applications. The investigations were conducted at various geometries, such as a bended cannula tubing, an impeller of a magnetically levitated rotary blood pump and tips of inflow cannulas. The oil film for the experimental validation was composed of black oil color and varnish. In the numerical simulation, color abrasion was displayed with a special post-processing tool by means of wall-attached pathlines. With the proper choice of numerical parameters, the computer simulations and the oil film method demonstrated good correlation. Improper generation of the simulation grid did lead to divergent results between the numerical simulation and the experiment. For the pump impeller as well as for the inflow cannulas, the calculation and the experiment showed similar flow patterns with backflow and stall zones. The oil film method represents a fast and simple approach to help validate numerical simulations of fluid flow. The experimentally generated near wall flow patterns can be easily compared with the solution of the CFD analysis.

  7. Bridging the Gap Between Validation and Implementation of Non-Animal Veterinary Vaccine Potency Testing Methods.

    Science.gov (United States)

    Dozier, Samantha; Brown, Jeffrey; Currie, Alistair

    2011-11-29

    In recent years, technologically advanced high-throughput techniques have been developed that replace, reduce or refine animal use in vaccine quality control tests. Following validation, these tests are slowly being accepted for use by international regulatory authorities. Because regulatory acceptance itself has not guaranteed that approved humane methods are adopted by manufacturers, various organizations have sought to foster the preferential use of validated non-animal methods by interfacing with industry and regulatory authorities. After noticing this gap between regulation and uptake by industry, we began developing a paradigm that seeks to narrow the gap and quicken implementation of new replacement, refinement or reduction guidance. A systematic analysis of our experience in promoting the transparent implementation of validated non-animal vaccine potency assays has led to the refinement of our paradigmatic process, presented here, by which interested parties can assess the local regulatory acceptance of methods that reduce animal use and integrate them into quality control testing protocols, or ensure the elimination of peripheral barriers to their use, particularly for potency and other tests carried out on production batches.

  8. Validation of a method for the analysis of biogenic amines: histamine instability during wine sample storage.

    Science.gov (United States)

    Bach, Benoit; Le Quere, Stephanie; Vuchot, Patrick; Grinbaum, Magali; Barnavon, Laurent

    2012-06-30

    This paper reports on the development of an optimized method for the simultaneous analysis of eight biogenic amines (histamine, methylamine, ethylamine, tyramine, putrescine, cadaverine, phenethylamine, and isoamylamine). The analytical method thus proposed has the following advantages: the easy derivatization of wine, the quantification of biogenic amines and a complete degradation of excess derivatization reagent during sample preparation in order to preserve the column. It consists in reversed phase separation by HPLC and UV-vis detection of the aminoenones formed by the reaction of amino compounds with the derivatization reagent diethyl ethoxymethylenemalonate (DEEMM). The usefulness of this technique was confirmed by an alternative oenological analytical method for the validation, quality control and uncertainty assessment (OIV Oeno 10/2005). The method was validated and proposed as a reference method to the International Organization of Vine and Wine (OIV). As a specific application of the proposed method, the biogenic amine content of Rhône valley wines was investigated. Copyright © 2011 Elsevier B.V. All rights reserved.

  9. Validation of methods for measurement of insulin secretion in humans in vivo

    DEFF Research Database (Denmark)

    Kjems, L L; Christiansen, E; Vølund, A

    2000-01-01

    ). These results indicate that both approaches provide accurate assessment of prehepatic ISRs in type 2 diabetic patients and control subjects. A simplified version of the deconvolution method based on standard kinetic parameters for C-peptide (Van Cauter et al.) was compared with the 2-day deconvolution method......)-considered the "gold standard"-and the combined model (by Vølund et al.). The deconvolution method is a 2-day method, which generally requires separate assessment of C-peptide kinetics, whereas the combined model is a single-day method that uses insulin and C-peptide data from a single test of interest. The validity...... similar whether measured during constant peripheral somatostatin infusion or without somatostatin infusion. Assessment of C-peptide kinetics can be performed without infusion of somatostatin, because the endogenous insulin concentration remains constant. Assessment of C-peptide kinetics with and without...

  10. Validity of the t-plot method to assess microporosity in hierarchical micro/mesoporous materials.

    Science.gov (United States)

    Galarneau, Anne; Villemot, François; Rodriguez, Jeremy; Fajula, François; Coasne, Benoit

    2014-11-11

    The t-plot method is a well-known technique which allows determining the micro- and/or mesoporous volumes and the specific surface area of a sample by comparison with a reference adsorption isotherm of a nonporous material having the same surface chemistry. In this paper, the validity of the t-plot method is discussed in the case of hierarchical porous materials exhibiting both micro- and mesoporosities. Different hierarchical zeolites with MCM-41 type ordered mesoporosity are prepared using pseudomorphic transformation. For comparison, we also consider simple mechanical mixtures of microporous and mesoporous materials. We first show an intrinsic failure of the t-plot method; this method does not describe the fact that, for a given surface chemistry and pressure, the thickness of the film adsorbed in micropores or small mesopores (abacus is given to correct the underestimated microporous volume by the t-plot method.

  11. Validation of simultaneous volumetric and spectrophotometric methods for the determination of captopril in pharmaceutical formulations.

    Science.gov (United States)

    Rahman, Nafisur; Singh, Manisha; Hoda, Nasrul

    2005-01-01

    Simple, sensitive and economical simultaneous volumetric and spectrophotometric methods for the determination of captopril have been developed. The methods were based on the reaction of captopril with potassium iodate in HCl medium. Amaranth was used as indicator to detect the end-point of the titration in aqueous layer. The iodine formed during the titration was extracted into CCl4 and subsequently determined spectrophotometrically at 510 nm. The Beer's law was obeyed in the concentration range of 120-520 microg ml-1. Rigorous statistical analyses were performed for the validation of the proposed methods. The proposed methods were successfully applied to the determination of captopril in dosage forms. Comparison of the means of the proposed procedures with those of reference methods using point and interval hypothesis tests showed no statistically significant difference.

  12. Diffuse reflectance near infrared-chemometric methods development and validation of amoxicillin capsule formulations

    Directory of Open Access Journals (Sweden)

    Ahmed Nawaz Khan

    2016-01-01

    Full Text Available Objective: The aim of present study was to establish near infrared-chemometric methods that could be effectively used for quality profiling through identification and quantification of amoxicillin (AMOX in formulated capsule which were similar to commercial products. In order to evaluate a large number of market products easily and quickly, these methods were modeled. Materials and Methods: Thermo Scientific Antaris II near infrared analyzer with TQ Analyst Chemometric Software were used for the development and validation of the identification and quantification models. Several AMOX formulations were composed with four excipients microcrystalline cellulose, magnesium stearate, croscarmellose sodium and colloidal silicon dioxide. Development includes quadratic mixture formulation design, near infrared spectrum acquisition, spectral pretreatment and outlier detection. According to prescribed guidelines by International Conference on Harmonization (ICH and European Medicine Agency (EMA developed methods were validated in terms of specificity, accuracy, precision, linearity, and robustness. Results: On diffuse reflectance mode, an identification model based on discriminant analysis was successfully processed with 76 formulations; and same samples were also used for quantitative analysis using partial least square algorithm with four latent variables and 0.9937 correlation of coefficient followed by 2.17% root mean square error of calibration (RMSEC, 2.38% root mean square error of prediction (RMSEP, 2.43% root mean square error of cross-validation (RMSECV. Conclusion: Proposed model established a good relationship between the spectral information and AMOX identity as well as content. Resulted values show the performance of the proposed models which offers alternate choice for AMOX capsule evaluation, relative to that of well-established high-performance liquid chromatography method. Ultimately three commercial products were successfully evaluated

  13. Validation of the Nuclear Design Method for MOX Fuel Loaded LWR Cores

    International Nuclear Information System (INIS)

    Saji, E.; Inoue, Y.; Mori, M.; Ushio, T.

    2001-01-01

    The actual batch loading of mixed-oxide (MOX) fuel in light water reactors (LWRs) is now ready to start in Japan. One of the efforts that have been devoted to realizing this batch loading has been validation of the nuclear design methods calculating the MOX-fuel-loaded LWR core characteristics. This paper summarizes the validation work for the applicability of the CASMO-4/SIMULATE-3 in-core fuel management code system to MOX-fuel-loaded LWR cores. This code system is widely used by a number of electric power companies for the core management of their commercial LWRs. The validation work was performed for both boiling water reactor (BWR) and pressurized water reactor (PWR) applications. Each validation consists of two parts: analyses of critical experiments and core tracking calculations of operating plants. For the critical experiments, we have chosen a series of experiments known as the VENUS International Program (VIP), which was performed at the SCK/CEN MOL laboratory in Belgium. VIP consists of both BWR and PWR fuel assembly configurations. As for the core tracking calculations, the operating data of MOX-fuel-loaded BWR and PWR cores in Europe have been utilized

  14. Optimisation and validation of methods to assess single nucleotide polymorphisms (SNPs) in archival histological material

    DEFF Research Database (Denmark)

    Andreassen, C N; Sørensen, Flemming Brandt; Overgaard, J

    2004-01-01

    only archival specimens are available. This study was conducted to validate protocols optimised for assessment of SNPs based on paraffin embedded, formalin fixed tissue samples. PATIENTS AND METHODS: In 137 breast cancer patients, three TGFB1 SNPs were assessed based on archival histological specimens...... precipitation). RESULTS: Assessment of SNPs based on archival histological material is encumbered by a number of obstacles and pitfalls. However, these can be widely overcome by careful optimisation of the methods used for sample selection, DNA extraction and PCR. Within 130 samples that fulfil the criteria...

  15. ANALYTICAL METHOD DEVELOPMENT AND VALIDATION FOR SIMULTANEOUS ESTIMATION OF SIMVASTATIN AND SITAGLIPTIN

    OpenAIRE

    Yaddanapudi Mrudula Devi; R. Karthikeyan; Punttaguntla Sreenivasa Babu

    2013-01-01

    A simple, specific, accurate, rapid, inexpensive isocratic Reversed Phase-High Performance Liquid Chromatography (RP-HPLC) method was developed and validated for the quantitative determination of Simvastatin and Sitagliptin pharmaceutical tablet dosage forms. RP-HPLC method was developed by using Inertsil ODS-3 C 18 (75 mm*4.6 mm) 5 microns Short column, Shimadzu LC-20AT Prominence Liquid Chromatograph. The mobile phase composed of 0.05 M Ammonium acetate: CAN 60:40. The flow rate was set to ...

  16. Validation of a method to determine methylmercury in fish tissues using gas chromatography

    International Nuclear Information System (INIS)

    Vega Bolannos, Luisa O.; Arias Verdes, Jose A.; Beltran Llerandi, Gilberto; Castro Diaz, Odalys; Moreno Tellez, Olga L.

    2000-01-01

    We validated a method to determine methylmercury in fish tissues using gas chromatography with an electron capture detector as described by the Association of Official Analytical Chemist (AOAC) International. The linear curve range was 0.02 to 1 g/ml and linear correlation coefficient was 0.9979. A 1 mg/kg methylmercury-contaminated fish sample was analyzed 20 times to determine repeatability of the method. The quantification limit was 0.16 mg/kg and detection limit was 0.06 ppm. Fish samples contaminated with 0.2 to 10 mg/kg methylmercury showed recovery indexes from 94.66 to 108.8%

  17. A validated HPTLC method for estimation of moxifloxacin hydrochloride in tablets.

    Science.gov (United States)

    Dhillon, Vandana; Chaudhary, Alok Kumar

    2010-10-01

    A simple HPTLC method having high accuracy, precision and reproducibility was developed for the routine estimation of moxifloxacin hydrochloride in the tablets available in market and was validated for various parameters according to ICH guidelines. moxifloxacin hydrochloride was estimated at 292 nm by densitometry using Silica gel 60 F254 as stationary phase and a premix of methylene chloride: methanol: strong ammonia solution and acetonitrile (10:10:5:10) as mobile phase. Method was found linear in a range of 9-54 nanograms with a correlation coefficient >0.99. The regression equation was: AUC = 65.57 × (Amount in nanograms) + 163 (r(2) = 0.9908).

  18. Numerical Validation of the Delaunay Normalization and the Krylov-Bogoliubov-Mitropolsky Method

    Directory of Open Access Journals (Sweden)

    David Ortigosa

    2014-01-01

    Full Text Available A scalable second-order analytical orbit propagator programme based on modern and classical perturbation methods is being developed. As a first step in the validation and verification of part of our orbit propagator programme, we only consider the perturbation produced by zonal harmonic coefficients in the Earth’s gravity potential, so that it is possible to analyze the behaviour of the mathematical expressions involved in Delaunay normalization and the Krylov-Bogoliubov-Mitropolsky method in depth and determine their limits.

  19. Pre-validation methods for developing a patient reported outcome instrument

    Directory of Open Access Journals (Sweden)

    Castillo Mayret M

    2011-08-01

    Full Text Available Abstract Background Measures that reflect patients' assessment of their health are of increasing importance as outcome measures in randomised controlled trials. The methodological approach used in the pre-validation development of new instruments (item generation, item reduction and question formatting should be robust and transparent. The totality of the content of existing PRO instruments for a specific condition provides a valuable resource (pool of items that can be utilised to develop new instruments. Such 'top down' approaches are common, but the explicit pre-validation methods are often poorly reported. This paper presents a systematic and generalisable 5-step pre-validation PRO instrument methodology. Methods The method is illustrated using the example of the Aberdeen Glaucoma Questionnaire (AGQ. The five steps are: 1 Generation of a pool of items; 2 Item de-duplication (three phases; 3 Item reduction (two phases; 4 Assessment of the remaining items' content coverage against a pre-existing theoretical framework appropriate to the objectives of the instrument and the target population (e.g. ICF; and 5 qualitative exploration of the target populations' views of the new instrument and the items it contains. Results The AGQ 'item pool' contained 725 items. Three de-duplication phases resulted in reduction of 91, 225 and 48 items respectively. The item reduction phases discarded 70 items and 208 items respectively. The draft AGQ contained 83 items with good content coverage. The qualitative exploration ('think aloud' study resulted in removal of a further 15 items and refinement to the wording of others. The resultant draft AGQ contained 68 items. Conclusions This study presents a novel methodology for developing a PRO instrument, based on three sources: literature reporting what is important to patient; theoretically coherent framework; and patients' experience of completing the instrument. By systematically accounting for all items dropped

  20. Validation of the Analytical Method for the Determination of Flavonoids in Broccoli

    Directory of Open Access Journals (Sweden)

    Tuszyńska Magdalena

    2014-09-01

    Full Text Available A simple, accurate and selective HPLC method was developed and validated for determination of quercetin and kaempferol, which are the main flavonols in broccoli. The separation was achieved on a reversed-phase C18 column using a mobile phase composed of methanol/water (60/40 and phosphoric acid 0.2% at a flow rate of 1.0 ml min-1. The detection was carried out on a DAD detector at 370 nm. This method was validated according to the requirements for new methods, which include selectivity, linearity, precision, accuracy, limit of detection and limit of quantitation. The current method demonstrates good linearity, with R2 > 0.99. The recovery is within 98.07-102.15% and 97.92-101.83% for quercetin and kaempferol, respectively. The method is selective, in that quercetin and kaempferol are well separated from other compounds of broccoli with good resolution. The low limit of detection and limit of quantitation of quercetin and kaempferol enable the detection and quantitation of these flavonoids in broccoli at low con–centrations.

  1. Validation of histamine determination Method in yoghurt using High Performance Liquid Chromatography

    Directory of Open Access Journals (Sweden)

    M Jahedinia

    2014-02-01

    Full Text Available Biogenic amines are organic, basic nitrogenous compounds of low molecular weight that are mainly generated by the enzymatic decarboxylation of amino acids by microorganisms. Dairy products are among the foods with the highest amine content. A wide variety of methods and procedures for determination of histamine and biogenic amines have been established. Amongst, HPLC method is considered as reference method. The aim of this study was to validate Reversed Phase HPLC method determination of histamine in yoghurt. The mobile phase consisted of acetonitrile/water (18:88 v/v and the flow rate was set at 0.5 ml/min using isocratic HPLC. Detection was carried out at 254 nm using UV-detector. Calibration curve that was constructed using peak area of standards was linear and value of correlation coefficient (r2 was estimated at 0.998. Good recoveries were observed for histamine under investigation at all spiking levels and average of recoveries was 84%. The RSD% value from repeatability test was found to be %4.4. Limit of detection and limit of quantitation were 0.14 and 0.42 µ/ml, respectively. The results of validation tests showed that the method is reliable and rapid for quantification of histamine in yoghurt.

  2. Development and Validation of HPTLC Method for Estimation of Tenoxicam and its Formulations.

    Science.gov (United States)

    Chandel, S; Barhate, C R; Srivastava, A R; Kulkarni, S R; Kulkarni, S K; Kapadia, C J

    2012-01-01

    A simple, precise, accurate and rapid high performance thin layer chromatographic method has been developed and validated for the estimation of tenoxicam in the microemulsion gels. Tenoxicam was chromatographed on silica gel 60 F(254) TLC plate, as a stationary phase. The mobile phase was toluene: ethyl acetate: formic acid (6:4:0.3 v/v/v), which gave a dense and compact spot of tenoxicam with a R(f) value of 0.38±0.03. The quantification was carried out at 379 nm. The method was validated in terms of linearity, accuracy, precision and specificity. To justify the suitability, accuracy and precision of the proposed method, recovery studies were performed at three concentration levels. Statistical analysis proved that the proposed method is accurate and reproducible with linearity in the range of 100 to 400 ng. The limit of detection and limit of quantification for tenoxicam were 25 and 50 μg/spot, respectively. The proposed method can be employed for the routine analysis of tenoxicam as well as in pharmaceutical formulations.

  3. Moxidectin residues in lamb tissues: Development and validation of analytical method by UHPLC-MS/MS.

    Science.gov (United States)

    Del Bianchi A Cruz, Michelle; Fernandes, Maria A M; de C Braga, Patricia A; Monteiro, Alda L G; Daniel, Daniela; Reyes, Felix G R

    2018-01-01

    The development and validation of a throughput method for the quantitation of moxidectin residues in lamb target tissues (muscle, kidney, liver and fat) was conducted using ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). To achieve higher recovery of the analyte from the matrices, a modified QuEChERS method was used for sample preparation. The chromatographic separation was achieved using a Zorbax Eclipse Plus C18 RRHD column with a mobile phase comprising 5mM ammonium formate solution +0.1% formic acid (A) and acetonitrile +0.1% formic acid (B) in a linear gradient program. Method validation was performed based on the Commission Decision 2002/657/EC and VICH GL49. To quantify the analyte, matrix-matched analytical curves were constructed with spiked blank tissues, with a limit of quantitation of 5ngg -1 and limit of detection of 1.5ngg -1 for all matrices. The linearity, decision limit, detection capability accuracy, and inter- and intra-day repeatability of the method are reported. The method was successfully applied to incurred lamb tissue samples (muscle, liver, kidney and fat) in a concentration range from 5 to 200μgkg -1 , which demonstrated its suitability for monitoring moxidectin residues in lamb tissues in health surveillance programs, as well as for pharmacokinetics and residue depletion studies. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Validation and comparison of intensity based methods for change detection in serial brain images

    Science.gov (United States)

    Lesjak, Žiga; Špiclin, Žiga; Likar, Boštjan; Pernuš, Franjo

    2014-03-01

    Detection of longitudinal changes in brain structures is a common clinical task when assessing the progress of cerebrovascular and neurodegenerative diseases, which manifest in appearing and disappearing white matter lesions (WMLs). Changes of WMLs are usually quanti ed by their manual outlines and compared across longi- tudinal, serial magnetic resonance (MR) brain images. Since manual outlining in 3D MR images is subjective and inaccurate, several automated methods were proposed so as to enhance the sensitivity, reliability and re- peatability of change detection of WMLs. However, the absence of publicly available synthetic or clinical MR image databases with corresponding ground truth of changes renders the validation and comparison of any new and existing automated methods highly subjective. In this paper, we focus on the validation and comparison of three state-of-the-art intensity based methods for detection of longitudinal changes of WMLs. To objectively assess the three methods we created several synthetic MR image databases using a generative lesion model, which was trained on manually outlined patches of WMLs in a clinical MR image database of 22 patients. Val- idation was also performed on clinical MR image database of MS patients. Performances of the three change detection methods were evaluated by computing the similarity index and sensitivity between the obtained and the ground truth binary change map. The obtained similarity indices were in the range of 0.40-0.77, which should be improved for clinical use, while the comparison of methods revealed that the intensity subtraction method achieved similar performance as the change vector analysis method, which employed two MR sequences for change detection. Third method was based on local steering kernels and exhibited stable performance both on synthetic and clinical MR image databases.

  5. Validated spectrophotometric methods for determination of sodium valproate based on charge transfer complexation reactions

    Science.gov (United States)

    Belal, Tarek S.; El-Kafrawy, Dina S.; Mahrous, Mohamed S.; Abdel-Khalek, Magdi M.; Abo-Gharam, Amira H.

    2016-02-01

    This work presents the development, validation and application of four simple and direct spectrophotometric methods for determination of sodium valproate (VP) through charge transfer complexation reactions. The first method is based on the reaction of the drug with p-chloranilic acid (p-CA) in acetone to give a purple colored product with maximum absorbance at 524 nm. The second method depends on the reaction of VP with dichlone (DC) in dimethylformamide forming a reddish orange product measured at 490 nm. The third method is based upon the interaction of VP and picric acid (PA) in chloroform resulting in the formation of a yellow complex measured at 415 nm. The fourth method involves the formation of a yellow complex peaking at 361 nm upon the reaction of the drug with iodine in chloroform. Experimental conditions affecting the color development were studied and optimized. Stoichiometry of the reactions was determined. The proposed spectrophotometric procedures were effectively validated with respect to linearity, ranges, precision, accuracy, specificity, robustness, detection and quantification limits. Calibration curves of the formed color products with p-CA, DC, PA and iodine showed good linear relationships over the concentration ranges 24-144, 40-200, 2-20 and 1-8 μg/mL respectively. The proposed methods were successfully applied to the assay of sodium valproate in tablets and oral solution dosage forms with good accuracy and precision. Assay results were statistically compared to a reference pharmacopoeial HPLC method where no significant differences were observed between the proposed methods and reference method.

  6. Validation and Recommendation of Methods to Measure Biogas Production Potential of Animal Manure

    Directory of Open Access Journals (Sweden)

    C. H. Pham

    2013-06-01

    Full Text Available In developing countries, biogas energy production is seen as a technology that can provide clean energy in poor regions and reduce pollution caused by animal manure. Laboratories in these countries have little access to advanced gas measuring equipment, which may limit research aimed at improving local adapted biogas production. They may also be unable to produce valid estimates of an international standard that can be used for articles published in international peer-reviewed science journals. This study tested and validated methods for measuring total biogas and methane (CH4 production using batch fermentation and for characterizing the biomass. The biochemical methane potential (BMP (CH4 NL kg−1 VS of pig manure, cow manure and cellulose determined with the Moller and VDI methods was not significantly different in this test (p>0.05. The biodegradability using a ratio of BMP and theoretical BMP (TBMP was slightly higher using the Hansen method, but differences were not significant. Degradation rate assessed by methane formation rate showed wide variation within the batch method tested. The first-order kinetics constant k for the cumulative methane production curve was highest when two animal manures were fermented using the VDI 4630 method, indicating that this method was able to reach steady conditions in a shorter time, reducing fermentation duration. In precision tests, the repeatability of the relative standard deviation (RSDr for all batch methods was very low (4.8 to 8.1%, while the reproducibility of the relative standard deviation (RSDR varied widely, from 7.3 to 19.8%. In determination of biomethane concentration, the values obtained using the liquid replacement method (LRM were comparable to those obtained using gas chromatography (GC. This indicates that the LRM method could be used to determine biomethane concentration in biogas in laboratories with limited access to GC.

  7. A gradient-based method for segmenting FDG-PET images: methodology and validation

    International Nuclear Information System (INIS)

    Geets, Xavier; Lee, John A.; Gregoire, Vincent; Bol, Anne; Lonneux, Max

    2007-01-01

    A new gradient-based method for segmenting FDG-PET images is described and validated. The proposed method relies on the watershed transform and hierarchical cluster analysis. To allow a better estimation of the gradient intensity, iteratively reconstructed images were first denoised and deblurred with an edge-preserving filter and a constrained iterative deconvolution algorithm. Validation was first performed on computer-generated 3D phantoms containing spheres, then on a real cylindrical Lucite phantom containing spheres of different volumes ranging from 2.1 to 92.9 ml. Moreover, laryngeal tumours from seven patients were segmented on PET images acquired before laryngectomy by the gradient-based method and the thresholding method based on the source-to-background ratio developed by Daisne (Radiother Oncol 2003;69:247-50). For the spheres, the calculated volumes and radii were compared with the known values; for laryngeal tumours, the volumes were compared with the macroscopic specimens. Volume mismatches were also analysed. On computer-generated phantoms, the deconvolution algorithm decreased the mis-estimate of volumes and radii. For the Lucite phantom, the gradient-based method led to a slight underestimation of sphere volumes (by 10-20%), corresponding to negligible radius differences (0.5-1.1 mm); for laryngeal tumours, the segmented volumes by the gradient-based method agreed with those delineated on the macroscopic specimens, whereas the threshold-based method overestimated the true volume by 68% (p = 0.014). Lastly, macroscopic laryngeal specimens were totally encompassed by neither the threshold-based nor the gradient-based volumes. The gradient-based segmentation method applied on denoised and deblurred images proved to be more accurate than the source-to-background ratio method. (orig.)

  8. Validated spectrophotometric methods for the evaluation of Oseltamivir counterfeit pharmaceutical capsules

    Directory of Open Access Journals (Sweden)

    Rasha M. Youssef

    2014-06-01

    Full Text Available Four rapid, reliable and economical spectrophotometric methods have been established for the quantitative determination of Oseltamivir phosphate (OST without the interference of ascorbic acid (ASC found in some of its counterfeit capsules. The first method involves the use of derivative spectrophotometry with the zero-crossing technique where OST was easily determined using its 1D (Δλ = 3 at 219 nm. The second method is based on a first-order derivative ratio spectrophotometry (1DD, Δλ = 5 where 218 nm was selected for its quantification, while the third method applies a more advanced spectrophotometric method based on the ratio difference spectrophotometry (RD in which the difference in absorbance ratio was measured between 217 and 210 nm. In the fourth method, difference spectrophotometric method (ΔA is applied by subtracting absorbance at 252 from that at 263 nm where the difference in absorbance was zero for ASC. The proposed methods were validated for linearity, accuracy, precision and selectivity. Synthetic mixtures of different proportions and commercial capsules were assayed by the proposed methods and the results revealed good accuracy and repeatability of the developed methods.

  9. Using deuterated PAH amendments to validate chemical extraction methods to predict PAH bioavailability in soils

    Energy Technology Data Exchange (ETDEWEB)

    Gomez-Eyles, Jose L., E-mail: j.l.gomezeyles@reading.ac.uk [University of Reading, School of Human and Environmental Sciences, Soil Research Centre, Reading, RG6 6DW Berkshire (United Kingdom); Collins, Chris D.; Hodson, Mark E. [University of Reading, School of Human and Environmental Sciences, Soil Research Centre, Reading, RG6 6DW Berkshire (United Kingdom)

    2011-04-15

    Validating chemical methods to predict bioavailable fractions of polycyclic aromatic hydrocarbons (PAHs) by comparison with accumulation bioassays is problematic. Concentrations accumulated in soil organisms not only depend on the bioavailable fraction but also on contaminant properties. A historically contaminated soil was freshly spiked with deuterated PAHs (dPAHs). dPAHs have a similar fate to their respective undeuterated analogues, so chemical methods that give good indications of bioavailability should extract the fresh more readily available dPAHs and historic more recalcitrant PAHs in similar proportions to those in which they are accumulated in the tissues of test organisms. Cyclodextrin and butanol extractions predicted the bioavailable fraction for earthworms (Eisenia fetida) and plants (Lolium multiflorum) better than the exhaustive extraction. The PAHs accumulated by earthworms had a larger dPAH:PAH ratio than that predicted by chemical methods. The isotope ratio method described here provides an effective way of evaluating other chemical methods to predict bioavailability. - Research highlights: > Isotope ratios can be used to evaluate chemical methods to predict bioavailability. > Chemical methods predicted bioavailability better than exhaustive extractions. > Bioavailability to earthworms was still far from that predicted by chemical methods. - A novel method using isotope ratios to assess the ability of chemical methods to predict PAH bioavailability to soil biota.

  10. Unexpected but Most Welcome: Mixed Methods for the Validation and Revision of the Participatory Evaluation Measurement Instrument

    Science.gov (United States)

    Daigneault, Pierre-Marc; Jacob, Steve

    2014-01-01

    Although combining methods is nothing new, more contributions about why and how to mix methods for validation purposes are needed. This article presents a case of validating the inferences drawn from the Participatory Evaluation Measurement Instrument, an instrument that purports to measure stakeholder participation in evaluation. Although the…

  11. The validated and sensitive HPLC-DAD method for determination of patulin in strawberries.

    Science.gov (United States)

    Sadok, Ilona; Szmagara, Agnieszka; Staniszewska, Magdalena Maria

    2018-04-15

    This work outlines HPLC coupled with DAD detection for accurate quantification of patulin (mycotoxin) in strawberries. The optimized extraction of fruit samples through the modified QuEChERS technique in acetonitrile acidified with acetic acid (1%, v/v) and citrate-buffered salts followed by dispersive solid phase extraction using a primary secondary amine and graphitized carbon is described. The method presents LOD and LOQ of 1.5 and 5µg/kg, respectively and has been validated in strawberry matrix at three concentration levels (5, 10 and 50µg/kg), according to SANTE/11945/2015 and the 2002/657/EC Decision requirements. All validated patulin levels show high percentage of patulin recovery. The validation procedure also includes the intermediate precision performed within three successive days in samples spiked with patulin. The developed method was applied for analysis of fresh and frozen strawberries purchased at local markets. Patulin level in analyzed samples was below the level of detection. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. An Anatomically Validated Brachial Plexus Contouring Method for Intensity Modulated Radiation Therapy Planning

    Energy Technology Data Exchange (ETDEWEB)

    Van de Velde, Joris, E-mail: joris.vandevelde@ugent.be [Department of Anatomy, Ghent University, Ghent (Belgium); Department of Radiotherapy, Ghent University, Ghent (Belgium); Audenaert, Emmanuel [Department of Physical Medicine and Orthopedic Surgery, Ghent University, Ghent (Belgium); Speleers, Bruno; Vercauteren, Tom; Mulliez, Thomas [Department of Radiotherapy, Ghent University, Ghent (Belgium); Vandemaele, Pieter; Achten, Eric [Department of Radiology, Ghent University, Ghent (Belgium); Kerckaert, Ingrid; D' Herde, Katharina [Department of Anatomy, Ghent University, Ghent (Belgium); De Neve, Wilfried [Department of Radiotherapy, Ghent University, Ghent (Belgium); Van Hoof, Tom [Department of Anatomy, Ghent University, Ghent (Belgium)

    2013-11-15

    Purpose: To develop contouring guidelines for the brachial plexus (BP) using anatomically validated cadaver datasets. Magnetic resonance imaging (MRI) and computed tomography (CT) were used to obtain detailed visualizations of the BP region, with the goal of achieving maximal inclusion of the actual BP in a small contoured volume while also accommodating for anatomic variations. Methods and Materials: CT and MRI were obtained for 8 cadavers positioned for intensity modulated radiation therapy. 3-dimensional reconstructions of soft tissue (from MRI) and bone (from CT) were combined to create 8 separate enhanced CT project files. Dissection of the corresponding cadavers anatomically validated the reconstructions created. Seven enhanced CT project files were then automatically fitted, separately in different regions, to obtain a single dataset of superimposed BP regions that incorporated anatomic variations. From this dataset, improved BP contouring guidelines were developed. These guidelines were then applied to the 7 original CT project files and also to 1 additional file, left out from the superimposing procedure. The percentage of BP inclusion was compared with the published guidelines. Results: The anatomic validation procedure showed a high level of conformity for the BP regions examined between the 3-dimensional reconstructions generated and the dissected counterparts. Accurate and detailed BP contouring guidelines were developed, which provided corresponding guidance for each level in a clinical dataset. An average margin of 4.7 mm around the anatomically validated BP contour is sufficient to accommodate for anatomic variations. Using the new guidelines, 100% inclusion of the BP was achieved, compared with a mean inclusion of 37.75% when published guidelines were applied. Conclusion: Improved guidelines for BP delineation were developed using combined MRI and CT imaging with validation by anatomic dissection.

  13. Validated spectrophotometric methods for simultaneous determination of Omeprazole, Tinidazole and Doxycycline in their ternary mixture

    Science.gov (United States)

    Lotfy, Hayam M.; Hegazy, Maha A.; Mowaka, Shereen; Mohamed, Ekram Hany

    2016-01-01

    A comparative study of smart spectrophotometric techniques for the simultaneous determination of Omeprazole (OMP), Tinidazole (TIN) and Doxycycline (DOX) without prior separation steps is developed. These techniques consist of several consecutive steps utilizing zero/or ratio/or derivative spectra. The proposed techniques adopt nine simple different methods, namely direct spectrophotometry, dual wavelength, first derivative-zero crossing, amplitude factor, spectrum subtraction, ratio subtraction, derivative ratio-zero crossing, constant center, and successive derivative ratio method. The calibration graphs are linear over the concentration range of 1-20 μg/mL, 5-40 μg/mL and 2-30 μg/mL for OMP, TIN and DOX, respectively. These methods are tested by analyzing synthetic mixtures of the above drugs and successfully applied to commercial pharmaceutical preparation. The methods that are validated according to the ICH guidelines, accuracy, precision, and repeatability, were found to be within the acceptable limits.

  14. Piezoelectric quartz crystal sensors applied for bioanalytical assays and characterization of affinity interactions

    Directory of Open Access Journals (Sweden)

    Skládal Petr

    2003-01-01

    Full Text Available This review presents piezoelectric quartz crystals as transducers suitable for development of different types of bioanalytical assays. The components of measuring systems for piezosensors are described together with providers of commercial equipment. The piezoelectric biosensors are summarized for determination of viruses, bacterial and other cells, proteins, nucleic acids and small molecules as drugs, hormones and pesticides. In addition to mass changes, some agglutination assays employing viscosity effects are addressed. Finally, the direct label-free and real-time monitoring of affinity interactions using piezosensors is presented. The theoretical background for determination of appropriate kinetic rate and equilibrium constants is shown and the approach is demonstrated on the interaction of antibody with the corresponding antigen (protein secalin. Several examples of affinity studies are provided, including interactions of proteins (antibody and antigens, receptors and ligands, nucleic acids (hybridization, intercalation of metal complexes, lipids and saccharide-based layers.

  15. The BioSentinel Bioanalytical Microsystem: Characterizing DNA Radiation Damage in Living Organisms Beyond Earth Orbit

    Science.gov (United States)

    Ricco, A. J.; Hanel, R.; Bhattacharya, S.; Boone, T.; Tan, M.; Mousavi, A.; Rademacher, A.; Schooley, A.; Klamm, B.; Benton, J.; hide

    2016-01-01

    We will present details and initial lab test results from an integrated bioanalytical microsystem designed to conduct the first biology experiments beyond low Earth orbit (LEO) since Apollo 17 (1972). The 14-kg, 12x24x37-cm BioSentinel spacecraft (Figure 1) assays radiation-responsive yeast in its science payload by measuring DNA double-strand breaks (DSBs) repaired via homologous recombination, a mechanism common to all eukaryotes including humans. S. cerevisiae (brewer's yeast) in 288 microwells are provided with nutrient and optically assayed for growth and metabolism via 3-color absorptimetry monthly during the 18-month mission. BioSentinel is one of several secondary payloads to be deployed by NASA's Exploration Mission 1 (EM-1) launch vehicle into approximately 0.95 AU heliocentric orbit in July 2018; it will communicate with Earth from up to 100 million km.

  16. Advances of Vibrational Circular Dichroism (VCD) in bioanalytical chemistry. A review.

    Science.gov (United States)

    Kurouski, Dmitry

    2017-10-16

    Vibrational Circular Dichroism (VCD) is a unique and relatively new spectroscopic technique that is capable of determining an absolute configuration of chiral molecules. VCD can be also used to determine structure of large macromolecules. This review highlights the most recent advances of VCD in bioanalytical chemistry. It shows that VCD is capable of unraveling supramolecular organization of peptides, proteins, saccharides, glycerophospholipids, polypeptide microcrystals, as well as amyloid fibrils and DNA. This review also demonstrates how VCD can be utilized to explore molecule-molecule interactions that determine mechanisms of chiral separations in chromatography. It aims to attract attention of scientists from all different research areas demonstrating the strength and capability of this very powerful spectroscopic technique. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. A New Statistical Method to Determine the Degree of Validity of Health Economic Model Outcomes against Empirical Data.

    Science.gov (United States)

    Corro Ramos, Isaac; van Voorn, George A K; Vemer, Pepijn; Feenstra, Talitha L; Al, Maiwenn J

    2017-09-01

    The validation of health economic (HE) model outcomes against empirical data is of key importance. Although statistical testing seems applicable, guidelines for the validation of HE models lack guidance on statistical validation, and actual validation efforts often present subjective judgment of graphs and point estimates. To discuss the applicability of existing validation techniques and to present a new method for quantifying the degrees of validity statistically, which is useful for decision makers. A new Bayesian method is proposed to determine how well HE model outcomes compare with empirical data. Validity is based on a pre-established accuracy interval in which the model outcomes should fall. The method uses the outcomes of a probabilistic sensitivity analysis and results in a posterior distribution around the probability that HE model outcomes can be regarded as valid. We use a published diabetes model (Modelling Integrated Care for Diabetes based on Observational data) to validate the outcome "number of patients who are on dialysis or with end-stage renal disease." Results indicate that a high probability of a valid outcome is associated with relatively wide accuracy intervals. In particular, 25% deviation from the observed outcome implied approximately 60% expected validity. Current practice in HE model validation can be improved by using an alternative method based on assessing whether the model outcomes fit to empirical data at a predefined level of accuracy. This method has the advantage of assessing both model bias and parameter uncertainty and resulting in a quantitative measure of the degree of validity that penalizes models predicting the mean of an outcome correctly but with overly wide credible intervals. Copyright © 2017 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

  18. The Dynamic Similitude Design Method of Thin Walled Structures and Experimental Validation

    Directory of Open Access Journals (Sweden)

    Zhong Luo

    2016-01-01

    Full Text Available For the applicability of dynamic similitude models of thin walled structures, such as engine blades, turbine discs, and cylindrical shells, the dynamic similitude design of typical thin walled structures is investigated. The governing equation of typical thin walled structures is firstly unified, which guides to establishing dynamic scaling laws of typical thin walled structures. Based on the governing equation, geometrically complete scaling law of the typical thin walled structure is derived. In order to determine accurate distorted scaling laws of typical thin walled structures, three principles are proposed and theoretically proved by combining the sensitivity analysis and governing equation. Taking the thin walled annular plate as an example, geometrically complete and distorted scaling laws can be obtained based on the principles of determining dynamic scaling laws. Furthermore, the previous five orders’ accurate distorted scaling laws of thin walled annular plates are presented and numerically validated. Finally, the effectiveness of the similitude design method is validated by experimental annular plates.

  19. A Component-Based Modeling and Validation Method for PLC Systems

    Directory of Open Access Journals (Sweden)

    Rui Wang

    2014-05-01

    Full Text Available Programmable logic controllers (PLCs are complex embedded systems that are widely used in industry. This paper presents a component-based modeling and validation method for PLC systems using the behavior-interaction-priority (BIP framework. We designed a general system architecture and a component library for a type of device control system. The control software and hardware of the environment were all modeled as BIP components. System requirements were formalized as monitors. Simulation was carried out to validate the system model. A realistic example from industry of the gates control system was employed to illustrate our strategies. We found a couple of design errors during the simulation, which helped us to improve the dependability of the original systems. The results of experiment demonstrated the effectiveness of our approach.

  20. Method validation in plasma source optical emission spectroscopy (ICP-OES) - From samples to results

    International Nuclear Information System (INIS)

    Pilon, Fabien; Vielle, Karine; Birolleau, Jean-Claude; Vigneau, Olivier; Labet, Alexandre; Arnal, Nadege; Adam, Christelle; Camilleri, Virginie; Amiel, Jeanine; Granier, Guy; Faure, Joel; Arnaud, Regine; Beres, Andre; Blanchard, Jean-Marc; Boyer-Deslys, Valerie; Broudic, Veronique; Marques, Caroline; Augeray, Celine; Bellefleur, Alexandre; Bienvenu, Philippe; Delteil, Nicole; Boulet, Beatrice; Bourgarit, David; Brennetot, Rene; Fichet, Pascal; Celier, Magali; Chevillotte, Rene; Klelifa, Aline; Fuchs, Gilbert; Le Coq, Gilles; Mermet, Jean-Michel

    2017-01-01

    Even though ICP-OES (Inductively Coupled Plasma - Optical Emission Spectroscopy) is now a routine analysis technique, requirements for measuring processes impose a complete control and mastering of the operating process and of the associated quality management system. The aim of this (collective) book is to guide the analyst during all the measurement validation procedure and to help him to guarantee the mastering of its different steps: administrative and physical management of samples in the laboratory, preparation and treatment of the samples before measuring, qualification and monitoring of the apparatus, instrument setting and calibration strategy, exploitation of results in terms of accuracy, reliability, data covariance (with the practical determination of the accuracy profile). The most recent terminology is used in the book, and numerous examples and illustrations are given in order to a better understanding and to help the elaboration of method validation documents

  1. Assessment of the validity of inelastic design analysis methods by comparisons of predictions with test results

    International Nuclear Information System (INIS)

    Corum, J.M.; Clinard, J.A.; Sartory, W.K.

    1976-01-01

    A description is given of some of the work under way in the United States to provide the necessary information to evaluate inelastic analysis methods and computer programs used in fast reactor component design, and typical comparisons of analysis predictions with inelastic structural test results are presented. It is emphasized throughout that rather than asking how valid, or correct, are the analytical predictions, one might more properly question whether or not the combination of the predictions and the associated high-temperature design criteria leads to an acceptable level of structural integrity. It is believed that in this context the analysis predictions are generally valid, even though exact correlations between predictions and actual behavior are not obtained and cannot be expected. Final judgment, however, must be reserved for the design analyst in each specific case

  2. Development and Validation of Spectrophotometric Methods for the Determination of Rasagiline in Pharmaceutical Preparations

    Directory of Open Access Journals (Sweden)

    Serife Evrim Kepekci Tekkeli

    2013-01-01

    Full Text Available This study presents three simple, rapid, and accurate spectrophotometric methods for the determination of Rasagiline (RSG in pharmaceutical preparations. The determination procedures depend on the reaction of RSG with chloranilic acid for method A, tetrachloro-1,4-benzoquinone for method B, and 7,7,8,8-tetracyanoquinodimethane for method C. The colored products were quantitated spectrophotometrically at 524, 535, and 843 nm for methods A, B, and C, respectively. Different variables affecting the reaction were optimized. Linearity ranges of the methods with good correlation coefficients (0.9988–0.9996 were observed as 25–300 µg mL−1, 25–350 µg mL−1, and 50–500 µg mL−1 for methods A, B, and C, respectively. The formation of products takes place through different mechanisms. The sites of interaction were confirmed by elemental analysis using IR and 1H-NMR spectroscopy. The validation of the methods was carried out in terms of specificity, linearity, accuracy, precision, robustness, limit of detection, and limit of quantitation. No interference was observed from concomitants usually present in dosage forms. The methods were applied successfully to the determination of RSG in pharmaceutical preparations.

  3. Validated stability-indicating spectrofluorimetric methods for the determination of ebastine in pharmaceutical preparations

    Science.gov (United States)

    2011-01-01

    Two sensitive, selective, economic, and validated spectrofluorimetric methods were developed for the determination of ebastine (EBS) in pharmaceutical preparations depending on reaction with its tertiary amino group. Method I involves condensation of the drug with mixed anhydrides (citric and acetic anhydrides) producing a product with intense fluorescence, which was measured at 496 nm after excitation at 388 nm. Method (IIA) describes quantitative fluorescence quenching of eosin upon addition of the studied drug where the decrease in the fluorescence intensity was directly proportional to the concentration of ebastine; the fluorescence quenching was measured at 553 nm after excitation at 457 nm. This method was extended to (Method IIB) to apply first and second derivative synchronous spectrofluorimetric method (FDSFS & SDSFS) for the simultaneous analysis of EBS in presence of its alkaline, acidic, and UV degradation products. The proposed methods were successfully applied for the determination of the studied compound in its dosage forms. The results obtained were in good agreement with those obtained by a comparison method. Both methods were utilized to investigate the kinetics of the degradation of the drug. PMID:21385439

  4. Validated Spectrophotometric Methods for Simultaneous Determination of Food Colorants and Sweeteners

    Directory of Open Access Journals (Sweden)

    Fatma Turak

    2013-01-01

    Full Text Available Two simple spectrophotometric methods have been proposed for simultaneous determination of two colorants (Indigotin and Brilliant Blue and two sweeteners (Acesulfame-K and Aspartame in synthetic mixtures and chewing gums without any prior separation or purification. The first method, derivative spectrophotometry (ZCDS, is based on recording the first derivative curves (for Indigotin, Brillant Blue, and Acesulfame-K and third-derivative curve (for Aspartame and determining each component using the zero-crossing technique. The other method, ratio derivative spectrophotometry (RDS, depends on application ratio spectra of first- and third-derivative spectrophotometry to resolve the interference due to spectral overlapping. Both colorants and sweeteners showed good linearity, with regression coefficients of 0.9992–0.9999. The LOD and LOQ values ranged from 0.05 to 0.33 μgmL−1 and from 0.06 to 0.47 μgmL−1, respectively. The intraday and interday precision tests produced good RSD% values (<0.81%; recoveries ranged from 99.78% to 100.67% for all two methods. The accuracy and precision of the methods have been determined, and the methods have been validated by analyzing synthetic mixtures containing colorants and sweeteners. Two methods were applied for the above combination, and satisfactory results were obtained. The results obtained by applying the ZCDS method were statistically compared with those obtained by the RDS method.

  5. Validated stability-indicating spectrofluorimetric methods for the determination of ebastine in pharmaceutical preparations

    Directory of Open Access Journals (Sweden)

    Eid Manal

    2011-03-01

    Full Text Available Abstract Two sensitive, selective, economic, and validated spectrofluorimetric methods were developed for the determination of ebastine (EBS in pharmaceutical preparations depending on reaction with its tertiary amino group. Method I involves condensation of the drug with mixed anhydrides (citric and acetic anhydrides producing a product with intense fluorescence, which was measured at 496 nm after excitation at 388 nm. Method (IIA describes quantitative fluorescence quenching of eosin upon addition of the studied drug where the decrease in the fluorescence intensity was directly proportional to the concentration of ebastine; the fluorescence quenching was measured at 553 nm after excitation at 457 nm. This method was extended to (Method IIB to apply first and second derivative synchronous spectrofluorimetric method (FDSFS & SDSFS for the simultaneous analysis of EBS in presence of its alkaline, acidic, and UV degradation products. The proposed methods were successfully applied for the determination of the studied compound in its dosage forms. The results obtained were in good agreement with those obtained by a comparison method. Both methods were utilized to investigate the kinetics of the degradation of the drug.

  6. Development and validation of NIR-chemometric methods for chemical and pharmaceutical characterization of meloxicam tablets.

    Science.gov (United States)

    Tomuta, Ioan; Iovanov, Rares; Bodoki, Ede; Vonica, Loredana

    2014-04-01

    Near-Infrared (NIR) spectroscopy is an important component of a Process Analytical Technology (PAT) toolbox and is a key technology for enabling the rapid analysis of pharmaceutical tablets. The aim of this research work was to develop and validate NIR-chemometric methods not only for the determination of active pharmaceutical ingredients content but also pharmaceutical properties (crushing strength, disintegration time) of meloxicam tablets. The development of the method for active content assay was performed on samples corresponding to 80%, 90%, 100%, 110% and 120% of meloxicam content and the development of the methods for pharmaceutical characterization was performed on samples prepared at seven different compression forces (ranging from 7 to 45 kN) using NIR transmission spectra of intact tablets and PLS as a regression method. The results show that the developed methods have good trueness, precision and accuracy and are appropriate for direct active content assay in tablets (ranging from 12 to 18 mg/tablet) and also for predicting crushing strength and disintegration time of intact meloxicam tablets. The comparative data show that the proposed methods are in good agreement with the reference methods currently used for the characterization of meloxicam tablets (HPLC-UV methods for the assay and European Pharmacopeia methods for determining the crushing strength and disintegration time). The results show the possibility to predict both chemical properties (active content) and physical/pharmaceutical properties (crushing strength and disintegration time) directly, without any sample preparation, from the same NIR transmission spectrum of meloxicam tablets.

  7. Validation of a food frequency questionnaire to determine vitamin D intakes using the method of triads.

    Science.gov (United States)

    Weir, R R; Carson, E L; Mulhern, M S; Laird, E; Healy, M; Pourshahidi, L K

    2016-04-01

    Dietary sources of vitamin D (both natural and fortified) are increasingly contributing to consumers' vitamin D intake and status. Therefore, the present study aimed to validate a vitamin D food frequency questionnaire (FFQ) for the assessment of habitual vitamin D intake. A total of 49 apparently healthy consenting adults (aged 18-64 years) from the local community were sampled at the end of winter. Dietary intakes were recorded using a 4-day weighed food record (4d-WFR) and a 17-item FFQ based on foods known to contribute to dietary vitamin D intake. Fasting vitamin D status was quantified by serum 25-hydroxyvitamin D [25(OH)D] using liquid chromatography tandem mass spectrometry. The method of triads was applied using these three measurements to determine the overall validity of the FFQ. Vitamin D intakes from 4d-WFR ranged between 0.42 and 31.65 μg day(-1), whereas intakes determined from the FFQ ranged from 1.03 to 36.08 μg day(-1). Serum 25(OH)D concentrations ranged between 12.89 and 279.00 nmol L(-1). The mean (SD) difference between the FFQ and 4d-WFR was +1.62 ( 3.86). There were strong correlations between the vitamin D intake estimated by the FFQ and that from the 4d-WFR (r = 0.562) and also with serum 25(OH)D concentrations (r = 0.567). Vitamin D intake estimated from the 4d-WFR was also strongly correlated with serum 25(OH)D concentrations (r = 0.411). The overall validity coefficient calculated using the method of triads was high (0.881). The vitamin D FFQ has been validated for use in future studies aiming to assess habitual vitamin D intake. © 2015 The British Dietetic Association Ltd.

  8. Raman fiber-optical method for colon cancer detection: Cross-validation and outlier identification approach.

    Science.gov (United States)

    Petersen, D; Naveed, P; Ragheb, A; Niedieker, D; El-Mashtoly, S F; Brechmann, T; Kötting, C; Schmiegel, W H; Freier, E; Pox, C; Gerwert, K

    2017-06-15

    Endoscopy plays a major role in early recognition of cancer which is not externally accessible and therewith in increasing the survival rate. Raman spectroscopic fiber-optical approaches can help to decrease the impact on the patient, increase objectivity in tissue characterization, reduce expenses and provide a significant time advantage in endoscopy. In gastroenterology an early recognition of malign and precursor lesions is relevant. Instantaneous and precise differentiation between adenomas as precursor lesions for cancer and hyperplastic polyps on the one hand and between high and low-risk alterations on the other hand is important. Raman fiber-optical measurements of colon biopsy samples taken during colonoscopy were carried out during a clinical study, and samples of adenocarcinoma (22), tubular adenomas (141), hyperplastic polyps (79) and normal tissue (101) from 151 patients were analyzed. This allows us to focus on the bioinformatic analysis and to set stage for Raman endoscopic measurements. Since spectral differences between normal and cancerous biopsy samples are small, special care has to be taken in data analysis. Using a leave-one-patient-out cross-validation scheme, three different outlier identification methods were investigated to decrease the influence of systematic errors, like a residual risk in misplacement of the sample and spectral dilution of marker bands (esp. cancerous tissue) and therewith optimize the experimental design. Furthermore other validations methods like leave-one-sample-out and leave-one-spectrum-out cross-validation schemes were compared with leave-one-patient-out cross-validation. High-risk lesions were differentiated from low-risk lesions with a sensitivity of 79%, specificity of 74% and an accuracy of 77%, cancer and normal tissue with a sensitivity of 79%, specificity of 83% and an accuracy of 81%. Additionally applied outlier identification enabled us to improve the recognition of neoplastic biopsy samples. Copyright

  9. Raman fiber-optical method for colon cancer detection: Cross-validation and outlier identification approach

    Science.gov (United States)

    Petersen, D.; Naveed, P.; Ragheb, A.; Niedieker, D.; El-Mashtoly, S. F.; Brechmann, T.; Kötting, C.; Schmiegel, W. H.; Freier, E.; Pox, C.; Gerwert, K.

    2017-06-01

    Endoscopy plays a major role in early recognition of cancer which is not externally accessible and therewith in increasing the survival rate. Raman spectroscopic fiber-optical approaches can help to decrease the impact on the patient, increase objectivity in tissue characterization, reduce expenses and provide a significant time advantage in endoscopy. In gastroenterology an early recognition of malign and precursor lesions is relevant. Instantaneous and precise differentiation between adenomas as precursor lesions for cancer and hyperplastic polyps on the one hand and between high and low-risk alterations on the other hand is important. Raman fiber-optical measurements of colon biopsy samples taken during colonoscopy were carried out during a clinical study, and samples of adenocarcinoma (22), tubular adenomas (141), hyperplastic polyps (79) and normal tissue (101) from 151 patients were analyzed. This allows us to focus on the bioinformatic analysis and to set stage for Raman endoscopic measurements. Since spectral differences between normal and cancerous biopsy samples are small, special care has to be taken in data analysis. Using a leave-one-patient-out cross-validation scheme, three different outlier identification methods were investigated to decrease the influence of systematic errors, like a residual risk in misplacement of the sample and spectral dilution of marker bands (esp. cancerous tissue) and therewith optimize the experimental design. Furthermore other validations methods like leave-one-sample-out and leave-one-spectrum-out cross-validation schemes were compared with leave-one-patient-out cross-validation. High-risk lesions were differentiated from low-risk lesions with a sensitivity of 79%, specificity of 74% and an accuracy of 77%, cancer and normal tissue with a sensitivity of 79%, specificity of 83% and an accuracy of 81%. Additionally applied outlier identification enabled us to improve the recognition of neoplastic biopsy samples.

  10. Validation of the analytical methods in the LWR code BOXER for gadolinium-loaded fuel pins

    International Nuclear Information System (INIS)

    Paratte, J.M.; Arkuszewski, J.J.; Kamboj, B.K.; Kallfelz, J.M.; Abdel-Khalik, S.I.

    1990-01-01

    Due to the very high absorption occurring in gadolinium-loaded fuel pins, calculations of lattices with such pins present are a demanding test of the analysis methods in light water reactor (LWR) cell and assembly codes. Considerable effort has, therefore, been devoted to the validation of code methods for gadolinia fuel. The goal of the work reported in this paper is to check the analysis methods in the LWR cell/assembly code BOXER and its associated cross-section processing code ETOBOX, by comparison of BOXER results with those from a very accurate Monte Carlo calculation for a gadolinium benchmark problem. Initial results of such a comparison have been previously reported. However, the Monte Carlo calculations, done with the MCNP code, were performed at Los Alamos National Laboratory using ENDF/B-V data, while the BOXER calculations were performed at the Paul Scherrer Institute using JEF-1 nuclear data. This difference in the basic nuclear data used for the two calculations, caused by the restricted nature of these evaluated data files, led to associated uncertainties in a comparison of the results for methods validation. In the joint investigations at the Georgia Institute of Technology and PSI, such uncertainty in this comparison was eliminated by using ENDF/B-V data for BOXER calculations at Georgia Tech

  11. Development and validation of a thin-layer chromatography method for stability studies of naproxen

    International Nuclear Information System (INIS)

    Rodriguez Hernandez, Yaslenis; Suarez Perez, Yania; Garcia Pulpeiro, Oscar; Rodriguez Borges, Tania

    2011-01-01

    The validation of an analytical method was carried out to be applied to the stability studies of the future formulations of naproxen suppositories for infant and adult use. The factors which mostly influenced in the naproxen stability were determined, the major degradation occurred in oxidizing acid medium and by action of light. The possible formation of esters between the free carboxyl group present in naproxen and the glyceryl monoestereate present in the base was identified as one of the degradation paths in the new formulation. The results were satisfactory. A thin-layer chromatography-based method was developed as well as the best chromatographic conditions were selected. GF 254 silica gel plates and ultraviolet developer at 254 nm were employed. Three solvent systems were evaluated of which A made up of glacial acetic: tetrahydrofurane:toluene (3:9:90 v/v/v)allowed adequate resolution between the analyte and the possible degradation products, with detection limit of 1 μg. The use of the suggested method was restricted to the identification of possible degradation products just for qualitative purposes and not as final test. The method proved to be sensitive and selective enough to be applied for the stated objective, according to the validation results

  12. A Validated HPLC-DAD Method for Simultaneous Determination of Etodolac and Pantoprazole in Rat Plasma

    Directory of Open Access Journals (Sweden)

    Ali S. Abdelhameed

    2014-01-01

    Full Text Available A simple, sensitive, and accurate HPLC-DAD method has been developed and validated for the simultaneous determination of pantoprazole and etodolac in rat plasma as a tool for therapeutic drug monitoring. Optimal chromatographic separation of the analytes was achieved on a Waters Symmetry C18 column using a mobile phase that consisted of phosphate buffer pH~4.0 as eluent A and acetonitrile as eluent B in a ratio of A : B, 55 : 45 v/v for 6 min, pumped isocratically at a flow rate of 0.8 mL min−1. The eluted analytes were monitored using photodiode array detector set to quantify samples at 254 nm. The method was linear with r2=0.9999 for PTZ and r2=0.9995 for ETD at a concentration range of 0.1–15 and 5–50 μgmL−1 for PTZ and ETD, respectively. The limits of detection were found to be 0.033 and 0.918 μgmL−1 for PTZ and ETD, respectively. The method was statistically validated for linearity, accuracy, precision, and selectivity following the International Conference for Harmonization (ICH guidelines. The reproducibility of the method was reliable with the intra- and interday precision (% RSD <7.76% for PTZ and <7.58 % for ETD.

  13. Method development and validation for dieckol in the standardization of phlorotannin preparations

    Directory of Open Access Journals (Sweden)

    Jiyoung Kim

    2016-03-01

    Full Text Available Abstract Phlorotannins are reported to have diverse biological properties. However, no analytical methods for the standardization of phlorotannin preparations have been reported. Herein, we developed and validated an analytical method for the determination of dieckol in phlorotannin extracts (PRT using high-performance liquid chromatography (HPLC. The optimum HPLC conditions consisted of a Supelco Discovery C18 column stationary phase, a mobile phase (A: 15 % HPLC grade methanol in deionized water, B: methanol, UV detection at 230 nm, and a flow rate of 0.7 mL/min. The optimized chromatographic conditions were validated and exhibited good specificity and linearity (R 2 > 0.9994–1.0000. The recoveries were in the range of 100.9–102.3 %. The method had good intermediate (%RSD 1.2 and intra-day (%RSD 0.4–1.7 assay precisions. This HPLC method had good accuracy and quality in the determination of dieckol in PRT.

  14. A validated HPLC method for separation and determination of promethazine enantiomers in pharmaceutical formulations.

    Science.gov (United States)

    Saleh, Ola A; El-Azzouny, Aida A; Aboul-Enein, Hassan Y; Badawy, Amr M

    2009-01-01

    A simple, rapid, and validated method for separation and determination of promethazine enantiomers was developed. Promethazine was separated and quantitated on a Vancomycin Chirobiotic V column (250 x 4.6 mm), using a mixture of methanol, acetic acid, and triethylamine (100:0.1:0.1%, by volume) as a mobile phase at 20 degrees C and at a flow rate of 1 mL/min. The UV-detector was set to 254 nm. Acetyl salicylic acid (Aspirin) was used as an internal standard. The applied HPLC method allowed separation and quantification of promethazine enantiomers with good linearity (r > .999) in the studied range. The relative standard deviations (RSD) were 0.29 and 0.36 for the promethazine enantiomers with accuracy of 100.06 and 100.08. The limit of detection and limit of quantification of promethazine enantiomers were found to be 0.04 and 0.07 microg/mL, respectively. The method was validated through the parameters of linearity, accuracy, precision, and robustness. The HPLC method was applied for the quantitative determination of promethazine in pharmaceutical formulations.

  15. Validation of a simple isotope method for estimating true calcium fractional absorption in adolescents.

    Science.gov (United States)

    Lee, W; McCabe, G P; Martin, B R; Weaver, C M

    2011-01-01

    We validated a single oral isotope method for estimating fractional calcium absorption determined by double isotope methods in adolescents. Developed equations with an oral isotope including a single blood draw or spot urine collection can be used to evaluate fractional calcium absorption in adolescents which allows flexibility in developing protocols. This study was designed to develop and validate a simpler, less expensive single oral isotope method for determining fractional calcium (Ca) absorption in adolescents. We used our database of 31 observations from ten white and 12 black adolescent girls aged 10-15 years who participated in metabolic and kinetic studies. Tracer data following oral ((44)Ca) and intravenous (IV, (42)Ca) administration of calcium stable isotopes and samples in serum and urine from various time points up to 4 days were used to develop methods using multiple regression analysis based on a single measurement of enriched stable isotope/tracee defined as tracer/tracee (TT) in serum (TT(serum)) or urine (TT(urine)). Reference values for fractional calcium absorption were from oral/IV stable isotope ratios in 24-h serum or urine and full kinetic modeling. The strongest equation using a single blood sample had R (2) = 0.94 (p single urine sample had R (2) = 0.95 (p single blood draw or urine collection for determining fractional calcium absorption were successfully validated in healthy, non-obese white and black adolescent girls aged 10-15 years. The equations well-predicted fractional calcium absorption in Asian adolescent boys and girls.

  16. Ecological content validation of the Information Assessment Method for parents (IAM-parent): A mixed methods study.

    Science.gov (United States)

    Bujold, M; El Sherif, R; Bush, P L; Johnson-Lafleur, J; Doray, G; Pluye, P

    2018-02-01

    This mixed methods study content validated the Information Assessment Method for parents (IAM-parent) that allows users to systematically rate and comment on online parenting information. Quantitative data and results: 22,407 IAM ratings were collected; of the initial 32 items, descriptive statistics showed that 10 had low relevance. Qualitative data and results: IAM-based comments were collected, and 20 IAM users were interviewed (maximum variation sample); the qualitative data analysis assessed the representativeness of IAM items, and identified items with problematic wording. Researchers, the program director, and Web editors integrated quantitative and qualitative results, which led to a shorter and clearer IAM-parent. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  17. Fisk-based criteria to support validation of detection methods for drinking water and air.

    Energy Technology Data Exchange (ETDEWEB)

    MacDonell, M.; Bhattacharyya, M.; Finster, M.; Williams, M.; Picel, K.; Chang, Y.-S.; Peterson, J.; Adeshina, F.; Sonich-Mullin, C.; Environmental Science Division; EPA

    2009-02-18

    This report was prepared to support the validation of analytical methods for threat contaminants under the U.S. Environmental Protection Agency (EPA) National Homeland Security Research Center (NHSRC) program. It is designed to serve as a resource for certain applications of benchmark and fate information for homeland security threat contaminants. The report identifies risk-based criteria from existing health benchmarks for drinking water and air for potential use as validation targets. The focus is on benchmarks for chronic public exposures. The priority sources are standard EPA concentration limits for drinking water and air, along with oral and inhalation toxicity values. Many contaminants identified as homeland security threats to drinking water or air would convert to other chemicals within minutes to hours of being released. For this reason, a fate analysis has been performed to identify potential transformation products and removal half-lives in air and water so appropriate forms can be targeted for detection over time. The risk-based criteria presented in this report to frame method validation are expected to be lower than actual operational targets based on realistic exposures following a release. Note that many target criteria provided in this report are taken from available benchmarks without assessing the underlying toxicological details. That is, although the relevance of the chemical form and analogues are evaluated, the toxicological interpretations and extrapolations conducted by the authoring organizations are not. It is also important to emphasize that such targets in the current analysis are not health-based advisory levels to guide homeland security responses. This integrated evaluation of chronic public benchmarks and contaminant fate has identified more than 200 risk-based criteria as method validation targets across numerous contaminants and fate products in drinking water and air combined. The gap in directly applicable values is

  18. Determination of methylmercury in marine sediment samples: Method validation and occurrence data

    International Nuclear Information System (INIS)

    Carrasco, Luis; Vassileva, Emilia

    2015-01-01

    Highlights: • A method for MeHg determination at trace level in marine sediments is completely validated. • Validation is performed according to ISO-17025 and Eurachem guidelines. • The extraction efficiency of four sample preparation procedures is evaluated. • The uncertainty budget is used as a tool for evaluation of main uncertainty contributors. • Comparison with independent methods yields good agreement within stated uncertainty. - Abstract: The determination of methylmercury (MeHg) in sediment samples is a difficult task due to the extremely low MeHg/THg (total mercury) ratio and species interconversion. Here, we present the method validation of a cost-effective fit-for-purpose analytical procedure for the measurement of MeHg in sediments, which is based on aqueous phase ethylation, followed by purge and trap and hyphenated gas chromatography–pyrolysis–atomic fluorescence spectrometry (GC–Py–AFS) separation and detection. Four different extraction techniques, namely acid and alkaline leaching followed by solvent extraction and evaporation, microwave-assisted extraction with 2-mercaptoethanol, and acid leaching, solvent extraction and back extraction into sodium thiosulfate, were examined regarding their potential to selectively extract MeHg from estuarine sediment IAEA-405 certified reference material (CRM). The procedure based on acid leaching with HNO 3 /CuSO 4 , solvent extraction and back extraction into Na 2 S 2 O 3 yielded the highest extraction recovery, i.e., 94 ± 3% and offered the possibility to perform the extraction of a large number of samples in a short time, by eliminating the evaporation step. The artifact formation of MeHg was evaluated by high performance liquid chromatography coupled to inductively coupled plasma mass spectrometry (HPLC–ICP–MS), using isotopically enriched Me 201 Hg and 202 Hg and it was found to be nonexistent. A full validation approach in line with ISO 17025 and Eurachem guidelines was followed

  19. Development and Validation of Liquid Chromatographic Method for Estimation of Naringin in Nanoformulation

    Directory of Open Access Journals (Sweden)

    Kranti P. Musmade

    2014-01-01

    Full Text Available A simple, precise, accurate, rapid, and sensitive reverse phase high performance liquid chromatography (RP-HPLC method with UV detection has been developed and validated for quantification of naringin (NAR in novel pharmaceutical formulation. NAR is a polyphenolic flavonoid present in most of the citrus plants having variety of pharmacological activities. Method optimization was carried out by considering the various parameters such as effect of pH and column. The analyte was separated by employing a C18 (250.0 × 4.6 mm, 5 μm column at ambient temperature in isocratic conditions using phosphate buffer pH 3.5: acetonitrile (75 : 25% v/v as mobile phase pumped at a flow rate of 1.0 mL/min. UV detection was carried out at 282 nm. The developed method was validated according to ICH guidelines Q2(R1. The method was found to be precise and accurate on statistical evaluation with a linearity range of 0.1 to 20.0 μg/mL for NAR. The intra- and interday precision studies showed good reproducibility with coefficients of variation (CV less than 1.0%. The mean recovery of NAR was found to be 99.33 ± 0.16%. The proposed method was found to be highly accurate, sensitive, and robust. The proposed liquid chromatographic method was successfully employed for the routine analysis of said compound in developed novel nanopharmaceuticals. The presence of excipients did not show any interference on the determination of NAR, indicating method specificity.

  20. Validity and reliability of different kinematics methods used for bike fitting.

    Science.gov (United States)

    Fonda, Borut; Sarabon, Nejc; Li, François-Xavier

    2014-01-01

    The most common bike fitting method to set the seat height is based on the knee angle when the pedal is in its lowest position, i.e. bottom dead centre (BDC). However, there is no consensus on what method should be used to measure the knee angle. Therefore, the first aim of this study was to compare three dynamic methods to each other and against a static method. The second aim was to test the intra-session reliability of the knee angle at BDC measured by dynamic methods. Eleven cyclists performed five 3-min cycling trials; three at different seat heights (25°, 30° and 35° knee angle at BDC according to static measure) and two at preferred seat height. Thirteen infrared cameras (3D), a high-speed camera (2D), and an electrogoniometer were used to measure the knee angle during pedalling, when the pedal was at the BDC. Compared to 3D kinematics, all other methods statistically significantly underestimated the knee angle (P = 0.00; η(2) = 0.73). All three dynamic methods have been found to be substantially different compared to the static measure (effect sizes between 0.4 and 0.6). All dynamic methods achieved good intra-session reliability. 2D kinematics is a valid tool for knee angle assessment during bike fitting. However, for higher precision, one should use correction factor by adding 2.2° to the measured value.

  1. Validation of the intrinsic spatial efficiency method for non cylindrical homogeneous sources using MC simulation

    Energy Technology Data Exchange (ETDEWEB)

    Ortiz-Ramírez, Pablo, E-mail: rapeitor@ug.uchile.cl; Ruiz, Andrés [Departamento de Física, Facultad de Ciencias, Universidad de Chile (Chile)

    2016-07-07

    The Monte Carlo simulation of the gamma spectroscopy systems is a common practice in these days. The most popular softwares to do this are MCNP and Geant4 codes. The intrinsic spatial efficiency method is a general and absolute method to determine the absolute efficiency of a spectroscopy system for any extended sources, but this was only demonstrated experimentally for cylindrical sources. Due to the difficulty that the preparation of sources with any shape represents, the simplest way to do this is by the simulation of the spectroscopy system and the source. In this work we present the validation of the intrinsic spatial efficiency method for sources with different geometries and for photons with an energy of 661.65 keV. In the simulation the matrix effects (the auto-attenuation effect) are not considered, therefore these results are only preliminaries. The MC simulation is carried out using the FLUKA code and the absolute efficiency of the detector is determined using two methods: the statistical count of Full Energy Peak (FEP) area (traditional method) and the intrinsic spatial efficiency method. The obtained results show total agreement between the absolute efficiencies determined by the traditional method and the intrinsic spatial efficiency method. The relative bias is lesser than 1% in all cases.

  2. Development and validation of an extraction method for the analysis of perfluoroalkyl substances in human hair.

    Science.gov (United States)

    Kim, Da-Hye; Oh, Jeong-Eun

    2017-05-01

    Human hair has many advantages as a non-invasive sample; however, analytical methods for detecting perfluoroalkyl substances (PFASs) in human hair are still in the development stage. Therefore, the aim of this study was to develop and validate a method for monitoring 11 PFASs in human hair. Solid-phase extraction (SPE), ion-pairing extraction (IPE), a combined method (SPE+IPE) and solvent extraction with ENVI-carb clean-up were compared to develop an optimal extraction method using two types of hair sample (powder and piece forms). Analysis of PFASs was performed using liquid chromatography and tandem mass spectrometry. Among the four different extraction procedures, the SPE method using powdered hair showed the best extraction efficiency and recoveries ranged from 85.8 to 102%. The method detection limits for the SPE method were 0.114-0.796 ng/g and good precision (below 10%) and accuracy (66.4-110%) were obtained. In light of these results, SPE is considered the optimal method for PFAS extraction from hair. It was also successfully used to detect PFASs in human hair samples. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. Validation of an analytical method for quality control and stability study of 10 % Phenylephrine eyedrops

    International Nuclear Information System (INIS)

    Monteagudo Licea, Raiza; Garcia Penna, Caridad Margarita; Botet Garcia, Martha

    2010-01-01

    Phenylephrine is used like mydiatric in eye examinations and other ophthalmic procedures. It is used as vasoconstrictor with local anesthetic agents. In present paper a high resolution liquid chromatography analytical method was validated to quality control and stability studies of 10 % Phenylephrine (eyedrops). Method was based in separation of active principle through a Lichrosorb RO-18 (5 μm) (250 x 4 mm) chromatography column with UV detection at 280 nm using a mobile phase composed by a non-gasified mixture of methanol distilled water (1:1) with 1.1 g of 1-sodium octane-sulphonate by liter adjusted to pH 3,0 with phosphoric acid at a flow speed of 1.0 mL/min. Analytical method was linear, accuracy, specific and exact in the interval of study concentrations

  4. Further validation of the hybrid particle-mesh method for vortex shedding flow simulations

    Directory of Open Access Journals (Sweden)

    Seung-Jae Lee

    2015-11-01

    Full Text Available This is the continuation of a numerical study on vortex shedding from a blunt trailing-edge of a hydrofoil. In our previous work (Lee et al., 2015, numerical schemes for efficient computations were successfully implemented; i.e. multiple domains, the approximation of domain boundary conditions using cubic spline functions, and particle- based domain decomposition for better load balancing. In this study, numerical results through a hybrid particle-mesh method which adopts the Vortex-In-Cell (VIC method and the Brinkman penalization model are further rigorously validated through comparison to experimental data at the Reynolds number of 2 × 106. The effects of changes in numerical parameters are also explored herein. We find that the present numerical method enables us to reasonably simulate vortex shedding phenomenon, as well as turbulent wakes of a hydrofoil.

  5. Design of passive directional acoustic devices using Topology Optimization - from method to experimental validation

    DEFF Research Database (Denmark)

    Christiansen, Rasmus Ellebæk; Fernandez Grande, Efren

    2016-01-01

    The paper presents a topology optimization based method for designing acoustic focusing devices, capable of tailoring the sound emission pattern of one or several sources, across a chosen frequency band. The method is demonstrated numerically considering devices optimized for directional sound...... emission in two dimensions and is experimentally validated using three dimensional prints of the optimized designs. The emitted fields exhibit a level difference of at least 15 dB on axis relative to the off-axis directions, over frequency bands of approximately an octave. It is demonstrated to be possible...... to design focusing devices of dimensions comparable to the acoustic wavelength, a frequency range which is typically problematic, as well as devices operating at higher frequencies. The classical parabolic reflector is used as a benchmark. The devices designed using the proposed method are shown...

  6. A New Validated RP- HPLC Method for the Determination of Nevirapine in Human Plasma

    Directory of Open Access Journals (Sweden)

    C. H. Venkata Kumar

    2010-01-01

    Full Text Available A rapid, selective and sensitive high performance liquid chromatographic method for the estimation of nevirapine in human plasma has been developed. Chromatography was carried out on a Hypersil BDS C18 column using a mixture of ammonium acetate buffer (pH 4.0 ± 0.05 and acetonitrile (85:15 v/v as the mobile phase. The eluents were monitored for the drug by UV detection at 254 nm. Oxcarbazepine was used as an internal standard for this study. The retention times for nevirapine and oxcarbazepine were found to be 7.2 and 14.7 min respectively. The method was found to be linear in the concentration range of 50 ng/mL to 5003.7 ng/mL. The method was validated as per FDA guidelines and was found to be suitable for bioequivalence and pharmacokinetic studies.

  7. Validation of analytical method for quality control of B12 Vitamin-10 000 injection

    International Nuclear Information System (INIS)

    Botet Garcia, Martha; Garcia Penna, Caridad Margarita; Troche Concepcion, Yenilen; Cannizares Arencibia, Yanara; Moreno Correoso, Barbara

    2009-01-01

    Analytical method reported by USA Pharmacopeia was validated for quality control of injectable B 1 2 Vitamin (10 000 U) by UV spectrophotometry because this is a simpler and low-cost method allowing quality control of finished product. Calibration curve was graphed at 60 to 140% interval, where it was linear with a correlation coefficient similar to 0, 9999; statistical test for interception and slope was considered non-significant. There was a recovery of 99.7 % in study concentrations interval where the Cochran (G) and Student(t) test were not significant too. Variation coefficient in repetition study was similar to 0.59 % for the 6 assayed replies, whereas in intermediate precision analysis, the Fisher and Student tests were not significant. Analytical method was linear, precise, specific and exact in study concentrations interval

  8. Analytical method validation for quality control and the study of the 50 mg Propylthiouracil stability

    International Nuclear Information System (INIS)

    Valdes Bendoyro, Maria Olga; Garcia Penna, Caridad Margarita; Fernandez, Juan Lugones; Garcia Borges, Lisandra; Martinez Espinosa, Vivian

    2010-01-01

    A high-performance liquid chromatography analytical method was developed and validated for the quality control and stability studies of 50 mg Propylthiouracil tablets. Method is based in active principle separation through a 100 RP-18 RP-18 (5 μm) (250 x 4 mm) Lichrospher chromatography with UV detection to 272 nm, using a mobile phase composed by a ungaseous mixture of a 0.025 M buffer solution-monobasic potassium phosphate to pH= 4,6 ad acetonitrile in a 80:20 ratio with a flux speed of 0,5 mL/min. Analytical method was linear, precise, specific and exact in the study concentrations interval

  9. Development and validation of a method to determine the boron isotopic composition of crop plants.

    Science.gov (United States)

    Rosner, Martin; Pritzkow, Wolfgang; Vogl, Jochen; Voerkelius, Susanne

    2011-04-01

    We present a comprehensive chemical and mass spectrometric method to determine boron isotopic compositions of plant tissue. The method including dry ashing, a three-step ion chromatographic boron-matrix separation, and (11)B/(10)B isotope ratio determinations using the Cs(2)BO(2)(+) graphite technique has been validated using certified reference and quality control materials. The developed method is capable to determine δ(11)B values in plant tissue down to boron concentrations of 1 mg/kg with an expanded uncertainty of ≤1.7‰ (k = 2). The determined δ(11)B values reveal an enormous isotopic range of boron in plant tissues covering three-quarters of the natural terrestrial occurring variation in the boron isotopic composition. As the local environment and anthropogenic activity mainly control the boron intake of plants, the boron isotopic composition of plants can be used for food provenance studies.

  10. A Validated RP-HPLC Method for theDetermination of Impurities in Montelukast Sodium

    Directory of Open Access Journals (Sweden)

    N. Rashmitha

    2010-01-01

    Full Text Available The present paper describes the development of a reverse phase chromatographic (RPLC method for montelukast sodium in the presence of its impurities and degradation products generated from forced degradation studies. The drug substance was subjected to stress conditions of hydrolysis, oxidation, photolysis and thermal degradation. The degradation of montelukast sodium was observed under acid and oxidative environment. The drug was found to be stable in other stress conditions studied. Successful separation of the drug from the process impurities and degradation products formed under stress conditions were achieved on an Atlantis dC18 (250 x 4.6 mm 5 μm column. The gradient LC method employs solution A and solution B as mobile phase. The solution A contains aqueous 0.1% OPA and solution B contains a mixture of water, acetonitrile (5:95 v/v. The HPLC method was developed and validated with respect to linearity, accuracy, precision, specificity and ruggedness.

  11. Fuzzy decision-making: a new method in model selection via various validity criteria

    International Nuclear Information System (INIS)

    Shakouri Ganjavi, H.; Nikravesh, K.

    2001-01-01

    Modeling is considered as the first step in scientific investigations. Several alternative models may be candida ted to express a phenomenon. Scientists use various criteria to select one model between the competing models. Based on the solution of a Fuzzy Decision-Making problem, this paper proposes a new method in model selection. The method enables the scientist to apply all desired validity criteria, systematically by defining a proper Possibility Distribution Function due to each criterion. Finally, minimization of a utility function composed of the Possibility Distribution Functions will determine the best selection. The method is illustrated through a modeling example for the A verage Daily Time Duration of Electrical Energy Consumption in Iran

  12. Development and validation of RP HPLC method for determination of betamethasone dipropionate in gingival crevicular fluid.

    Science.gov (United States)

    Bogdanovska, Liljana; Popovska, Mirjana; Dimitrovska, Aneta; Petkovska, Rumenka

    2013-09-01

    Abstract A simple RP HPLC method for quantification of betamethasone dipropionate (BDP) in gingival crevicular fluid (GCF) has been developed and validated. GCF represents a valuable matrix for therapeutic monitoring of drugs used in the treatment of periodontal disease. The proposed method involves single step extraction for sample preparation. The calibration curve for BDP was linear over the concentration range of 0.10-2.00 μg mL⁻¹ (R² = 0.9971). RSD values of intra- and inter-day precision ranged 2.2-4.5 and 1.6-5.7 %, while accuracy values were higher than 96.6 and 97.0 %, respectively. The described method can be successfully applied for determination of betamethasone concentrations in GCF obtained from patients with chronic periodontitis after local treatment with BDP cream 0.5 mg g⁻¹.

  13. Method validation and uncertainty evaluation of organically bound tritium analysis in environmental sample.

    Science.gov (United States)

    Huang, Yan-Jun; Zeng, Fan; Zhang, Bing; Chen, Chao-Feng; Qin, Hong-Juan; Wu, Lian-Sheng; Guo, Gui-Yin; Yang, Li-Tao; Shang-Guan, Zhi-Hong

    2014-08-01

    The analytical method for organically bound tritium (OBT) was developed in our laboratory. The optimized operating conditions and parameters were established for sample drying, special combustion, distillation, and measurement on a liquid scintillation spectrometer (LSC). Selected types of OBT samples such as rice, corn, rapeseed, fresh lettuce and pork were analyzed for method validation of recovery rate reproducibility, the minimum detection concentration, and the uncertainty for typical low level environmental sample was evaluated. The combustion water recovery rate of different dried environmental sample was kept at about 80%, the minimum detection concentration of OBT ranged from 0.61 to 0.89 Bq/kg (dry weight), depending on the hydrogen content. It showed that this method is suitable for OBT analysis of environmental sample with stable recovery rate, and the combustion water yield of a sample with weight about 40 g would provide sufficient quantity for measurement on LSC. Copyright © 2014 Elsevier Ltd. All rights reserved.

  14. Validation of a residue method to determine pesticide residues in cucumber by using nuclear techniques

    International Nuclear Information System (INIS)

    Baysoyu, D.; Tiryaki, O.; Secer, E.; Aydin, G.

    2009-01-01

    In this study, a multi-residue method using ethyl acetate for extraction and gel permeation chromatography for clean-up was validated to determine chlorpyrifos, malathion and dichlorvos in cucumber by gas chromatography. For this purpose, homogenized cucumber samples were fortified with pesticides at 0.02 0.2, 0.8 and 1 mg/kg levels. The efficiency and repeatability of the method in extraction and cleanup steps were performed using 1 4C-carbaryl by radioisotope tracer technique. 1 4C-carbaryl recoveries after the extraction and cleanup steps were between 92.63-111.73 % with a repeatability of 4.85% (CV) and 74.83-102.22 % with a repeatability of 7.19% (CV), respectively. The homogeneity of analytical samples and the stability of pesticides during homogenization were determined using radio tracer technique and chromatographic methods, respectively.

  15. Experimental methods to validate measures of emotional state and readiness for duty in critical operations

    International Nuclear Information System (INIS)

    Weston, Louise Marie

    2007-01-01

    A recent report on criticality accidents in nuclear facilities indicates that human error played a major role in a significant number of incidents with serious consequences and that some of these human errors may be related to the emotional state of the individual. A pre-shift test to detect a deleterious emotional state could reduce the occurrence of such errors in critical operations. The effectiveness of pre-shift testing is a challenge because of the need to gather predictive data in a relatively short test period and the potential occurrence of learning effects due to a requirement for frequent testing. This report reviews the different types of reliability and validity methods and testing and statistical analysis procedures to validate measures of emotional state. The ultimate value of a validation study depends upon the percentage of human errors in critical operations that are due to the emotional state of the individual. A review of the literature to identify the most promising predictors of emotional state for this application is highly recommended

  16. Development and Validation Dissolution Analytical Method of Nimesulide beta-Cyclodextrin 400 mg Tablet

    Directory of Open Access Journals (Sweden)

    Carlos Eduardo Carvalho Pereira

    2016-10-01

    Full Text Available The nimesulide (N-(4-nitro-2-phenoxyphenylmethanesulfonamide belongs to the class of non-steroidal anti-inflammatory drugs (NSAIDs and category II of the biopharmaceutical classification, The complexation of nimesulide with b-cyclodextrin is a pharmacological strategy to increase the solubility of the drug The objective of this study was to develop and validate an analytical methodology for dissolving the nimesulide beta-cyclodextrin 400 mg tablet and meets the guidelines of ANVISA for drug registration purposes. Once developed, the dissolution methodology was validated according to the RE of parameters no.  899/2003. In the development of the method it was noted that the duration of the dissolution test was 60 minutes, the volume and the most suitable dissolution medium was 900 mL of aqueous solution of sodium lauryl sulfate 1% (w/ v. It was also noted that rotation of 100 rpm and the paddle apparatus was the most appropriate to evaluate the dissolution of the drug. Spectrophotometric methodology was used to quantify the percentage of dissolved drug. The wavelength was 390 nm using the quantification. The validation of the methodology, system suitability parameters, specificity/selectivity, linearity, precision, accuracy and robustness were satisfactory and proved that the developed dissolution methodology was duly executed. DOI: http://dx.doi.org/10.17807/orbital.v8i5.827

  17. Validation of quantitative method for azoxystrobin residues in green beans and peas.

    Science.gov (United States)

    Abdelraheem, Ehab M H; Hassan, Sayed M; Arief, Mohamed M H; Mohammad, Somaia G

    2015-09-01

    This study presents a method validation for extraction and quantitative analysis of azoxystrobin residues in green beans and peas using HPLC-UV and the results confirmed by GC-MS. The employed method involved initial extraction with acetonitrile after the addition of salts (magnesium sulfate and sodium chloride), followed by a cleanup step by activated neutral carbon. Validation parameters; linearity, matrix effect, LOQ, specificity, trueness and repeatability precision were attained. The spiking levels for the trueness and the precision experiments were (0.1, 0.5, 3 mg/kg). For HPLC-UV analysis, mean recoveries ranged between 83.69% to 91.58% and 81.99% to 107.85% for green beans and peas, respectively. For GC-MS analysis, mean recoveries ranged from 76.29% to 94.56% and 80.77% to 100.91% for green beans and peas, respectively. According to these results, the method has been proven to be efficient for extraction and determination of azoxystrobin residues in green beans and peas. Copyright © 2015 Elsevier Ltd. All rights reserved.

  18. Absolute quantification method and validation of airborne snow crab allergen tropomyosin using tandem mass spectrometry.

    Science.gov (United States)

    Abdel Rahman, Anas M; Lopata, Andreas L; Randell, Edward W; Helleur, Robert J

    2010-11-29

    Measuring the levels of the major airborne allergens of snow crab in the workplace is very important in studying the prevalence of crab asthma in workers. Previously, snow crab tropomyosin (SCTM) was identified as the major aeroallergen in crab plants and a unique signature peptide was identified for this protein. The present study advances our knowledge on aeroallergens by developing a method of quantification of airborne SCTM by using isotope dilution mass spectrometry. Liquid chromatography tandem mass spectrometry was developed for separation and analysis of the signature peptides. The tryptic digestion conditions were optimized to accomplish complete digestion. The validity of the method was studied using international conference on harmonization protocol, Where 2-9% for CV (precision) and 101-110% for accuracy, at three different levels of quality control. Recovery of the spiked protein from PTFE and TopTip filters was measured to be 99% and 96%, respectively. To further demonstrate the applicability and the validity of the method for real samples, 45 kg of whole snow crab were processed in an enclosed (simulated) crab processing line and air samples were collected. The levels of SCTM ranged between 0.36-3.92 μg m(-3) and 1.70-2.31 μg m(-3) for butchering and cooking stations, respectively. Crown Copyright © 2010. Published by Elsevier B.V. All rights reserved.

  19. Validated HPTLC method for the simultaneous determination of cinnarizine and dimenhydrinate in their combined dosage form

    Directory of Open Access Journals (Sweden)

    Dina S. El-Kafrawy

    2016-02-01

    Full Text Available A simple, rapid and selective high performance thin layer chromatography (HPTLC method was developed for the simultaneous determination of cinnarizine (CNZ and dimenhydrinate (DMH in pure form and in their combined dosage form. Reviewing the literature revealed that there are no reports for the use of TLC for the assay of this mixture. Effective separation was achieved using Fluka HPTLC aluminum sheets of silica gel 60 F254 using chloroform–n-hexane–methanol (8.5:0.8:0.7, by volume as mobile phase, followed by densitometric measurement of CNZ and DMH spots at 254 and 279 nm, respectively. The reliability and analytical performance of the proposed HPTLC method were statistically validated with respect to linearity, ranges, precision, accuracy, selectivity, robustness and detection and quantification limits. Calibration curves were linear in the ranges of 50–400 and 50–500 ng/spot for CNZ and DMH, respectively with correlation coefficients >0.9998. The limits of detection were 8.1 and 8.0 ng/spot for CNZ and DMH respectively. The validated HPTLC method was applied to the simultaneous analysis of CNZ and DMH in laboratory-prepared tablets. Both analytes were successfully quantified with good recovery values, and no interference was encountered from the inactive ingredients.

  20. Identification, synthesis and characterization of process related desfluoro impurity of ezetimibe and HPLC method validations

    Directory of Open Access Journals (Sweden)

    Esen Bellur Atici

    2015-12-01

    Full Text Available Ezetimibe, which selectively inhibits cholesterol absorption across the intestinal wall and is used as an antihyperlipidemic agent, is synthesized for commercial use as a drug substance in highly pure form. During the synthetic process development studies of ezetimibe, an impurity was detected in the final product at levels ranging from 0.05% to 0.15% in reverse phase gradient high performance liquid chromatography (HPLC method and its molecular weight was determined by LC–MS analysis. The impurity was identified as (3R,4S-3-((S-3-(4-fluorophenyl-3-hydroxypropyl-4-(4-hydroxyphenyl-1-phenylazetidin-2-one which is called desfluoro ezetimibe (lactam-related impurity, synthesized and characterized, the mechanism of its formation was discussed in detail. After all standardization procedures, it was used as a reference standard during validation of HPLC method and routine analyses. In addition, content of Eze-1 desfluoro impurity in Eze-1 intermediates was specified as 0.10% to keep the formation of desfluoro ezetimibe impurity under control and the related substances HPLC method was validated accordingly.

  1. A Validated Method for the Quality Control of Andrographis paniculata Preparations.

    Science.gov (United States)

    Karioti, Anastasia; Timoteo, Patricia; Bergonzi, Maria Camilla; Bilia, Anna Rita

    2017-10-01

    Andrographis paniculata is a herbal drug of Asian traditional medicine largely employed for the treatment of several diseases. Recently, it has been introduced in Europe for the prophylactic and symptomatic treatment of common cold and as an ingredient of dietary supplements. The active principles are diterpenes with andrographolide as the main representative. In the present study, an analytical protocol was developed for the determination of the main constituents in the herb and preparations of A. paniculata . Three different extraction protocols (methanol extraction using a modified Soxhlet procedure, maceration under ultrasonication, and decoction) were tested. Ultrasonication achieved the highest content of analytes. HPLC conditions were optimized in terms of solvent mixtures, time course, and temperature. A reversed phase C18 column eluted with a gradient system consisting of acetonitrile and acidified water and including an isocratic step at 30 °C was used. The HPLC method was validated for linearity, limits of quantitation and detection, repeatability, precision, and accuracy. The overall method was validated for precision and accuracy over at least three different concentration levels. Relative standard deviation was less than 1.13%, whereas recovery was between 95.50% and 97.19%. The method also proved to be suitable for the determination of a large number of commercial samples and was proposed to the European Pharmacopoeia for the quality control of Andrographidis herba. Georg Thieme Verlag KG Stuttgart · New York.

  2. Self-validated Variance-based Methods for Sensitivity Analysis of Model Outputs

    Energy Technology Data Exchange (ETDEWEB)

    Tong, C

    2009-04-20

    Global sensitivity analysis (GSA) has the advantage over local sensitivity analysis in that GSA does not require strong model assumptions such as linearity or monotonicity. As a result, GSA methods such as those based on variance decomposition are well-suited to multi-physics models, which are often plagued by large nonlinearities. However, as with many other sampling-based methods, inadequate sample size can badly pollute the result accuracies. A natural remedy is to adaptively increase the sample size until sufficient accuracy is obtained. This paper proposes an iterative methodology comprising mechanisms for guiding sample size selection and self-assessing result accuracy. The elegant features in the the proposed methodology are the adaptive refinement strategies for stratified designs. We first apply this iterative methodology to the design of a self-validated first-order sensitivity analysis algorithm. We also extend this methodology to design a self-validated second-order sensitivity analysis algorithm based on refining replicated orthogonal array designs. Several numerical experiments are given to demonstrate the effectiveness of these methods.

  3. Validation of the EIR LWR calculation methods for criticality assessment of storage pools

    International Nuclear Information System (INIS)

    Grimm, P.; Paratte, J.M.

    1986-11-01

    The EIR code system for the calculation of light water reactors is presented and the methods used are briefly described. The application of the system to various types of critical experiments and benchmark problems proves its good accuracy, even for heterogeneous configurations containing strong neutron absorbers such as Boral. Since the multiplication factor k eff is normally somewhat overpredicted and the spread of the results is small, this code system is validated for the calculation of storage pools, taking into account a safety margins of 1.5% on k eff . (author)

  4. Validation of the LWR-EIR methods for the evaluation of compact beds

    International Nuclear Information System (INIS)

    Foskolos, K.; Grimm, P.; Maeder, C.; Paratte, J.M.

    1983-10-01

    The EIR code system for the calculation of light water reactors is presented and the methods used are briefly described. The application of the system on various types of critical experiments and benchmark problems proves its good precision, even for heterogeneous configurations with strong neutron absorbers like Boral. As the accuracy of the multiplication factor ksub(eff) is always better than 0.5% for normal LWR configurations, this code system is validated for the calculation of such configurations with a safety margin of 1.5% on ksub(eff). (Auth.)

  5. Development and Validation of New RP-HPLC Method for the Determination of Dexrazoxane

    OpenAIRE

    Basaveswara Rao, M. V.; Prasanthi, V.; Rao, G. Venkata; Raman, B. V.

    2012-01-01

    A new sensitive, precise, rapid and linear RP-HPLC method was developed and validated for the determination of dexrazoxane in formulations and human serum samples. Good chromatographic separation of dexrazoxane was achieved by using Kromasil C18 column. The system was operated at ambient temperature using a mobile phase consisting of methanol, 5% ortho phosphoric acid, 0.01M ammonium dihydrogen phosphate and tetrahydrofuran, pH 4.2 (10:40:30:20, v/v) isocratically at a flow rate of 1 ml/min. ...

  6. A simple method for validation and verification of pipettes mounted on automated liquid handlers

    OpenAIRE

    Stangegaard, Michael; Hansen, Anders Johannes; Frøslev, Tobias Guldberg; Morling, Niels

    2009-01-01

     We have implemented a simple method for validation and verification of the performance of pipettes mounted on automated liquid handlers as necessary for laboratories accredited under ISO 17025. An 8-step serial dilution of Orange G was prepared in quadruplicates in a flat bottom 96-well microtiter plate (BD Falcon) manually by means of calibrated pipettes. Each pipette of the liquid handler (1 up to 8) dispensed a selected volume (1 to 200µl) of Orange G 8 times into the wells of the microti...

  7. MR-based Water Content Estimation in Cartilage: Design and Validation of a Method

    DEFF Research Database (Denmark)

    Shiguetomi Medina, Juan Manuel; Kristiansen, Maja Sofie; Ringgaard, Steffen

    2012-01-01

    system (the closest to the body temperature) we measured, using the modified MR sequences, the T1 map intensity signal on 6 cartilage samples from living animals (pig) and on 8 gelatin samples which water content was already known. For the data analysis a T1 intensity signal map software analyzer...... was costumed and programmed. Finally, we validated the method after measuring and comparing 3 more cartilage samples in a living animal (pig). The obtained data was analyzed and the water content calculated. Then, the same samples were freeze-dried (this technique allows to take out all the water that a tissue...

  8. Simple Methods for Scanner Drift Normalization Validated for Automatic Segmentation of Knee Magnetic Resonance Imaging

    DEFF Research Database (Denmark)

    Dam, Erik Bjørnager

    2018-01-01

    Scanner drift is a well-known magnetic resonance imaging (MRI) artifact characterized by gradual signal degradation and scan intensity changes over time. In addition, hardware and software updates may imply abrupt changes in signal. The combined effects are particularly challenging for automatic...... for segmentation of knee MRI using the fully automatic KneeIQ framework. The validation included a total of 1975 scans from both high-field and low-field MRI. The results demonstrated that the pre-processing method denoted Atlas Affine Normalization significantly removed scanner drift effects and ensured...

  9. Validated spectophotometric methods for the assay of cinitapride hydrogen tartrate in pharmaceuticals

    Directory of Open Access Journals (Sweden)

    Satyanarayana K.V.V.

    2013-01-01

    Full Text Available Three simple, selective and rapid spectrophotometric methods have been established for the determination of cinitapride hydrogen tartrate (CHT in pharmaceutical tablets. The proposed methods are based on the diazotization of CHT with sodium nitrite and hydrochloric acid, followed by coupling with resorcinol, 1-benzoylacetone and 8-hydroxyquinoline in alkaline medium for methods A, B and C respectively. The formed azo dyes are measured at 442, 465 and 552 nm for methods A, B and C respectively. The parameters that affect the reaction were carefully optimized. Under optimum conditions, Beer’s law is obeyed over the ranges 2.0-32.0, 1.0-24.0 and 1.0-20.0 μg. mL-1 for methods A, B, and C, respectively. The calculated molar absorptivity values are 1.2853 x104, 1.9624 x104 and 3.92 x104 L.mol-1.cm-1 for methods A, B and C, respectively. The results of the proposed procedures were validated statistically according to ICH guidelines. The proposed methods were successfully applied to the determination of CHT in Cintapro tablets without interference from common excipients encountered.

  10. Estimating incidence from prevalence in generalised HIV epidemics: methods and validation.

    Directory of Open Access Journals (Sweden)

    Timothy B Hallett

    2008-04-01

    Full Text Available HIV surveillance of generalised epidemics in Africa primarily relies on prevalence at antenatal clinics, but estimates of incidence in the general population would be more useful. Repeated cross-sectional measures of HIV prevalence are now becoming available for general populations in many countries, and we aim to develop and validate methods that use these data to estimate HIV incidence.Two methods were developed that decompose observed changes in prevalence between two serosurveys into the contributions of new infections and mortality. Method 1 uses cohort mortality rates, and method 2 uses information on survival after infection. The performance of these two methods was assessed using simulated data from a mathematical model and actual data from three community-based cohort studies in Africa. Comparison with simulated data indicated that these methods can accurately estimates incidence rates and changes in incidence in a variety of epidemic conditions. Method 1 is simple to implement but relies on locally appropriate mortality data, whilst method 2 can make use of the same survival distribution in a wide range of scenarios. The estimates from both methods are within the 95% confidence intervals of almost all actual measurements of HIV incidence in adults and young people, and the patterns of incidence over age are correctly captured.It is possible to estimate incidence from cross-sectional prevalence data with sufficient accuracy to monitor the HIV epidemic. Although these methods will theoretically work in any context, we have able to test them only in southern and eastern Africa, where HIV epidemics are mature and generalised. The choice of method will depend on the local availability of HIV mortality data.

  11. Arab Scientific Working Group for Forensic Toxicology (ASWGFT: Guidelines for Method Validation in Forensic Toxicology

    Directory of Open Access Journals (Sweden)

    Abdulsallam A. Bakdash

    2018-01-01

    Full Text Available Reliable results and valid analytical data are an essential requirement for proper interpretation of forensic toxicology cases, especially when evaluating scientific studies and daily routine work, and when presenting any toxicological findings as a criminal evidence. In contrast, the results of unreliable analyses can be disputed in court and can also lead to unfair legal judgments against the defendant, or can result in wrong treatment in cases of rehabilitation for patients. In order to establish strong evidence and make a correct decision, the lab is asked to give high quality data that are based on reliable analytical methods. For that reason, all new analytical methods used in forensic toxicology, including the clinical diagnosis of causes of death, require careful care during the development of the analytical method and during its application. This is also an urgent need in the context of quality management and accreditation, especially as those issues have become increasingly important in the science of poisons and drug analysis in recent years. The Arab Society for forensic sciences and forensic medicine (ASFSFM will publish the first version of Guidelines for Method Validation in Forensic Toxicology issued by the Arab Scientific Working Group of Forensic Toxicology (ASWGFT. This aims to be a distinguished scientific publication written in Arabic which introducing the scientific terms of analytical methods in the field of forensic toxicology to Arab readers. The Arab Scientific Working Group of Forensic Toxicology has chosen the first issue to be a manual of guidelines for method validation in forensic toxicology, similar to the international organizations who are actively publishing in this field. The guidelines contain a systematic scientific message that can be published and circulated among Arab laboratories. It will also encourage other Arab scientific working groups in the field of forensic sciences to produce similar publications

  12. Chemometric approach for development, optimization, and validation of different chromatographic methods for separation of opium alkaloids.

    Science.gov (United States)

    Acevska, J; Stefkov, G; Petkovska, R; Kulevanova, S; Dimitrovska, A

    2012-05-01

    The excessive and continuously growing interest in the simultaneous determination of poppy alkaloids imposes the development and optimization of convenient high-throughput methods for the assessment of the qualitative and quantitative profile of alkaloids in poppy straw. Systematic optimization of two chromatographic methods (gas chromatography (GC)/flame ionization detector (FID)/mass spectrometry (MS) and reversed-phase (RP)-high-performance liquid chromatography (HPLC)/diode array detector (DAD)) for the separation of alkaloids from Papaver somniferum L. (Papaveraceae) was carried out. The effects of various conditions on the predefined chromatographic descriptors were investigated using chemometrics. A full factorial linear design of experiments for determining the relationship between chromatographic conditions and the retention behavior of the analytes was used. Central composite circumscribed design was utilized for the final method optimization. By conducting the optimization of the methods in very rational manner, a great deal of excessive and unproductive laboratory research work was avoided. The developed chromatographic methods were validated and compared in line with the resolving power, sensitivity, accuracy, speed, cost, ecological aspects, and compatibility with the poppy straw extraction procedure. The separation of the opium alkaloids using the GC/FID/MS method was achieved within 10 min, avoiding any derivatization step. This method has a stronger resolving power, shorter analysis time, better cost/effectiveness factor than the RP-HPLC/DAD method and is in line with the "green trend" of the analysis. The RP-HPLC/DAD method on the other hand displayed better sensitivity for all tested alkaloids. The proposed methods provide both fast screening and an accurate content assessment of the six alkaloids in the poppy samples obtained from the selection program of Papaver strains.

  13. Validation of capillary electrophoresis method for determination of N-methylpyrrolidine in cefepime for injection.

    Science.gov (United States)

    Prasanna, S John; Sharma, Hemant Kr; Mukkanti, K; Kumar, V Jagadeesh; Raja, G; Sivakumaran, M

    2010-11-01

    The present study relates to a new capillary electrophoresis method for the determination of N-methylpyrrolidine, an impurity considered to be toxic and also potential degradation impurity in cefepime hydrochloride drug substance. The newly developed capillary electrophoresis method for determining the content of N-methylpyrrolidine in cefepime for injection has been validated as per International Conference on Harmonization (ICH) guidelines to prove the selectivity, sensitivity, suitability, robustness, and ruggedness of the method. This simple, efficient, and rapid methodology may be used by pharmaceutical industry for routine analysis as well as during stability studies. The newly developed capillary electrophoresis method to determine the content of N-methylpyrrolidine in cefepime for injection requires 10 min for data acquisition, and uses an indirect UV photometry method to detect the analyte signal at 240 nm against the reference signal at 210 nm. The electrophoretic system is optimized to get stable base line, higher signal to noise ratio and peaks with narrow peak width. The method employs bare fused silica capillary with extended light path, effective length of capillary is 56 cm and inner diameter of capillary is 50 μm, 5 mmole of imidazole buffer adjusted to pH 5.1 with 3 molar acetic acid solution is used as background electrolyte. The sample is introduced in hydrodynamic mode employing pressure of 50 mbar for 5 s, and the desired separation is achieved with constant applied voltage of 25 kV at ambient temperature (~25°C).

  14. Rodgers' evolutionary concept analysis--a valid method for developing knowledge in nursing science.

    Science.gov (United States)

    Tofthagen, Randi; Fagerstrøm, Lisbeth M

    2010-12-01

    In nursing science, concept development is a necessary prerequisite for meaningful basic research. Rodgers' evolutionary concept analysis is a method for developing knowledge in nursing science. The purpose of this article is to present Rodgers' evolutionary concept analysis as a valid scientific method. A brief description of the evolutionary process, from data collection to data analysis, with the concepts' context, surrogate and related terms, antecedents, attributes, examples and consequences, is presented. The phases used in evolutionary concept analysis are illustrated with eight actual studies (1999-2009) from nursing research. The strength of the method is that it is systematic, with a focus on clear-cut phases during the analysis process, and that it can contribute to clarifying, describing and explaining concepts central to nursing science by analysing how a chosen concept has been used both within the discipline itself and other health sciences. While an interdisciplinary perspective which stresses the similarities and dissimilarities of how a concept is used in various disciplines can increase knowledge of a concept, it is important to clarify the specific with the discipline. Nursing research should focus on the unambiguous use of concepts, for which Rodgers' method constitutes a possible method. The importance of using quality criteria to determine the inclusion of material should, however, be emphasised in the continued development of the method. © 2010 The Authors. Scandinavian Journal of Caring Sciences © 2010 Nordic College of Caring Science.

  15. VALIDATION OF ULTRAVIOLET SPECTROPHOTOMETRY METHOD FOR DETERMINATION OF MEFENAMIC ACID LEVEL IN SUSPENSION DOSAGE FORMS

    Directory of Open Access Journals (Sweden)

    Nerdy

    2017-03-01

    Full Text Available Mefenamic Acid is one type of nonsteroidal antiinflammatory drug that works to relieve pain by blocking an enzyme that produces prostaglandins. The quality requirements that must be met by pharmaceutical preparations are levels contained must meet the level requirement as listed in the Indonesian Pharmacopoeia or other standard books. The purpose of this study was to conduct a validation test of ultraviolet spectrophotometry methods for determination of the Mefenamic Acid level in the suspension preparation. The sample consisted of three suspensions preparation under the trade name obtained from a pharmacy in the Medan city. The solvent used is sodium hydroxide (NaOH 0,1 N solution and the measurement was done at a wavelength of 286 nm. Validation parameters determined were Accuracy, Precision, Linearity, Range, Limit of Detection and Limit of Quantitation. The results of the determination of the Mefenamic Acid suspension preparation under the trade name Pondex® was 100,39±0,21%, trade name Omestan® was 99,98±0,33% and trade name Novastan® was 103,21±0,83%. All the suspension preparations were determined meet the general level requirement, that contain not less than 90,0% and not more than 110,0% of the amount stated on the label. The results meet the requirements of the validation test of analysis methods with the parameter percent recovery 100,08% for accuracy, relative standard deviation 0,04% for precision, the correlation coefficient 1,0000 for linearity, range 8 μg/mL to 12 μg/mL, limit of detection limit 0,0118 μg/mL, limit of quantitation 0,0356 μg/mL.

  16. Validation of methods performance for routine biochemistry analytes at Cobas 6000 analyzer series module c501.

    Science.gov (United States)

    Supak Smolcic, Vesna; Bilic-Zulle, Lidija; Fisic, Elizabeta

    2011-01-01

    Cobas 6000 (Roche, Germany) is biochemistry analyzer for spectrophotometric, immunoturbidimetric and ion-selective determination of biochemical analytes. Hereby we present analytical validation with emphasis on method performance judgment for routine operation. Validation was made for 30 analytes (metabolites, enzymes, trace elements, specific proteins and electrolytes). Research included determination of within-run (N = 20) and between-run imprecision (N = 30), inaccuracy (N = 30) and method comparison with routine analyzer (Beckman Coulter AU640) (N = 50). For validation of complete analytical process we calculated total error (TE). Results were judged according to quality specification criteria given by European Working Group. Within-run imprecision CVs were all below 5% except for cholesterol, triglycerides, IgA and IgM. Between-run CVs for all analytes were below 10%. Analytes that did not meet the required specifications for imprecision were: total protein, albumin, calcium, sodium, chloride, immunoglobulins and HDL cholesterol. Analytes that did not fulfill requirements for inaccuracy were: total protein, calcium, sodium and chloride. Analytes that deviated from quality specifications for total error were: total protein, albumin, calcium, sodium, chloride and IgM. Passing-Bablok regression analysis provided linear equation and 95% confidence interval for intercept and slope. Complete accordance with routine analyzer Beckman Coulter AU640 showed small number of analytes. Other analytes showed small proportional and/or small constant difference and therefore need to be adjusted for routine operation. Regarding low CV values, tested analyzer has satisfactory accuracy and precision and is extremely stable. Except for analytes that are coherent on both analyzers, some analytes require adjustments of slope and intercept for complete accordance.

  17. Design, development and method validation of a novel multi-resonance microwave sensor for moisture measurement.

    Science.gov (United States)

    Peters, Johanna; Taute, Wolfgang; Bartscher, Kathrin; Döscher, Claas; Höft, Michael; Knöchel, Reinhard; Breitkreutz, Jörg

    2017-04-08

    Microwave sensor systems using resonance technology at a single resonance in the range of 2-3 GHz have been shown to be a rapid and reliable tool for moisture determination in solid materials including pharmaceutical granules. So far, their application is limited to lower moisture ranges or limitations above certain moisture contents had to be accepted. Aim of the present study was to develop a novel multi-resonance sensor system in order to expand the measurement range. Therefore, a novel sensor using additional resonances over a wide frequency band was designed and used to investigate inherent limitations of first generation sensor systems and material-related limits. Using granule samples with different moisture contents, an experimental protocol for calibration and validation of the method was established. Pursuant to this protocol, a multiple linear regression (MLR) prediction model built by correlating microwave moisture values to the moisture determined by Karl Fischer titration was chosen and rated using conventional criteria such as coefficient of determination (R 2 ) and root mean square error of calibration (RMSEC). Using different operators, different analysis dates and different ambient conditions the method was fully validated following the guidance of ICH Q2(R1). The study clearly showed explanations for measurement uncertainties of first generation sensor systems which confirmed the approach to overcome these by using additional resonances. The established prediction model could be validated in the range of 7.6-19.6%, demonstrating its fit for its future purpose, the moisture content determination during wet granulations. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Quantitative Tagless Copurification: A Method to Validate and Identify Protein-Protein Interactions*

    Science.gov (United States)

    Shatsky, Maxim; Dong, Ming; Liu, Haichuan; Yang, Lee Lisheng; Choi, Megan; Singer, Mary E.; Geller, Jil T.; Fisher, Susan J.; Hall, Steven C.; Hazen, Terry C.; Brenner, Steven E.; Butland, Gareth; Jin, Jian; Witkowska, H. Ewa; Chandonia, John-Marc; Biggin, Mark D.

    2016-01-01

    Identifying protein-protein interactions (PPIs) at an acceptable false discovery rate (FDR) is challenging. Previously we identified several hundred PPIs from affinity purification - mass spectrometry (AP-MS) data for the bacteria Escherichia coli and Desulfovibrio vulgaris. These two interactomes have lower FDRs than any of the nine interactomes proposed previously for bacteria and are more enriched in PPIs validated by other data than the nine earlier interactomes. To more thoroughly determine the accuracy of ours or other interactomes and to discover further PPIs de novo, here we present a quantitative tagless method that employs iTRAQ MS to measure the copurification of endogenous proteins through orthogonal chromatography steps. 5273 fractions from a four-step fractionation of a D. vulgaris protein extract were assayed, resulting in the detection of 1242 proteins. Protein partners from our D. vulgaris and E. coli AP-MS interactomes copurify as frequently as pairs belonging to three benchmark data sets of well-characterized PPIs. In contrast, the protein pairs from the nine other bacterial interactomes copurify two- to 20-fold less often. We also identify 200 high confidence D. vulgaris PPIs based on tagless copurification and colocalization in the genome. These PPIs are as strongly validated by other data as our AP-MS interactomes and overlap with our AP-MS interactome for D.vulgaris within 3% of expectation, once FDRs and false negative rates are taken into account. Finally, we reanalyzed data from two quantitative tagless screens of human cell extracts. We estimate that the novel PPIs reported in these studies have an FDR of at least 85% and find that less than 7% of the novel PPIs identified in each screen overlap. Our results establish that a quantitative tagless method can be used to validate and identify PPIs, but that such data must be analyzed carefully to minimize the FDR. PMID:27099342

  19. Amphenicols stability in medicated feed – development and validation of liquid chromatography method

    Directory of Open Access Journals (Sweden)

    Pietro Wojciech Jerzy

    2014-12-01

    Full Text Available A liquid chromatography-ultraviolet detection method for the determination of florfenicol (FF and thiamphenicol (TAP in feeds is presented. The method comprises the extraction of analytes from the matrix with a mixture of methanol and acetonitrile, drying of the extract, and its dissolution in phosphate buffer. The analysis was performed with a gradient programme of the mobile phase composed of acetonitrile and buffer (pH = 7.3 on a Zorbax Eclipse Plus C18 (150 × 4.6 mm, 5 μm analytical column with UV (λ = 220 nm detection. The analytical procedure has been successfully adopted and validated for quantitative determination of florfenicol and thiamphenicol in feed samples. Sensitivity, specificity, linearity, repeatability, and intralaboratory reproducibility were included in the validation. The mean recovery of amphenicols was 93.5% within the working range of 50-4000 mg/kg. Simultaneous determination of chloramphenicol, which is banned in the feed, was also included within the same procedure of FF and TAP stability studies. Storing the medicated feed at room temperature for up to one month decreased concentration in the investigated drugs even by 45%. These findings are relevant to successful provision of therapy to animals.

  20. The establishment of tocopherol reference intervals for Hungarian adult population using a validated HPLC method.

    Science.gov (United States)

    Veres, Gábor; Szpisjak, László; Bajtai, Attila; Siska, Andrea; Klivényi, Péter; Ilisz, István; Földesi, Imre; Vécsei, László; Zádori, Dénes

    2017-09-01

    Evidence suggests that decreased α-tocopherol (the most biologically active substance in the vitamin E group) level can cause neurological symptoms, most likely ataxia. The aim of the current study was to first provide reference intervals for serum tocopherols in the adult Hungarian population with appropriate sample size, recruiting healthy control subjects and neurological patients suffering from conditions without symptoms of ataxia, myopathy or cognitive deficiency. A validated HPLC method applying a diode array detector and rac-tocol as internal standard was utilized for that purpose. Furthermore, serum cholesterol levels were determined as well for data normalization. The calculated 2.5-97.5% reference intervals for α-, β/γ- and δ-tocopherols were 24.62-54.67, 0.81-3.69 and 0.29-1.07 μm, respectively, whereas the tocopherol/cholesterol ratios were 5.11-11.27, 0.14-0.72 and 0.06-0.22 μmol/mmol, respectively. The establishment of these reference intervals may improve the diagnostic accuracy of tocopherol measurements in certain neurological conditions with decreased tocopherol levels. Moreover, the current study draws special attention to the possible pitfalls in the complex process of the determination of reference intervals as well, including the selection of study population, the application of internal standard and method validation and the calculation of tocopherol/cholesterol ratios. Copyright © 2017 John Wiley & Sons, Ltd.

  1. Validation of high performance liquid chromatography method for determination of meloxicam loaded PEGylated nanocapsules

    Directory of Open Access Journals (Sweden)

    Francine Rodrigues Ianiski

    2015-12-01

    Full Text Available abstract A method to ensure that an analytical method will produce reliable and interpretable information about the sample must first be validated, making sure that the results can be trusted and traced. In this study, we propose to validate an analytical high performance liquid chromatography (HPLC method for the quantitation of meloxicam loaded PEGylated nanocapsules(M-PEGNC. We performed a validation study, evaluated parameters including specificity, linearity, quantification limit, detection limit, accuracy, precision and robustness. PEGylated nanocapsules were prepared by interfacial deposition of preformed polymer, and the particle size, polydispersity index, zeta potential, pH value and encapsulation efficiency were characterized. The proposed HPLC method provides selective, linear results in the range of 1.0-40.0 μg/mL; quantification and detection limits were 1.78 μg/mL and 0.59 μg/mL, respectively; relative standard deviation for repeatability was 1.35% and intermediate precision was 0.41% and 0.61% for analyst 1 and analyst 2, respectively; accuracy between 99.23 and 101.79%; robustness between 97.13 and 98.45% for the quantification of M-PEGNC. Mean particle diameters were 261 ± 13 nm and 249 ± 20 nm, polydispersity index was 0.15 ± 0.07 and 0.17 ± 0.06, pH values were 5.0 ± 0.2 and 5.2 ± 0.1, and zeta-potential values were -37.9 ± 3.2 mV e -31.8 ± 2.8 mV for M-PEGNC and placebo(B-PEGNC, respectively. In conclusion, the proposed analytical method is suitable for the quality control of M-PEGNC. Moreover, suspensions showed monomodal size distributions and low polydispersity index indicating high homogeneity of formulations with narrow size distributions, and appropriate pH and zeta potential. The extraction process was efficient for release of meloxicam from nanostructured systems.

  2. How valid and applicable are current diagnostic criteria and assessment methods for dentin hypersensitivity? An overview.

    Science.gov (United States)

    Gernhardt, Christian R

    2013-03-01

    Although dentin hypersensitivity is a common clinical condition and is generally reported by the patient after experiencing a sharp, short pain caused by one of several different external stimuli, it is often inadequately understood. The purpose of this paper is to discuss different available diagnostic approaches and assessment methods used in order to suggest a basis to diagnose, monitor, and measure these challenging painful conditions related to dentin hypersensitivity in daily practice and scientific projects properly. A PubMed literature search strategy including the following MeSH terms were used as follows: "dentin sensitivity"[MeSH Terms] OR "dentin"[All Fields] AND "sensitivity"[All Fields] OR "dentin sensitivity"[All Fields] OR "dentin"[All Fields] AND "hypersensitivity"[All Fields] OR "dentin hypersensitivity"[All Fields] AND "diagnosis"[Subheading] OR "diagnosis"[All Fields] OR "diagnosis"[MeSH Terms] AND "assessment"[All Fields] AND ("methods"[Subheading] OR "methods"[All Fields] OR "methods"[MeSH Terms]. Furthermore, alternative terms such as "validity," "reliability," "root," "cervical," "diagnostic criteria," and "hypersensitivities" were additionally evaluated. The literature search, also including the alternative terms and journals, revealed only a small number of specific papers related to valid diagnosis, diagnostic criteria, and assessment methods of dentin hypersensitivity. Outcomes from these publications showed that the response to different stimuli varies substantially from one person to another and is, due to individual factors, often difficult to assess correctly. Furthermore, the cause of the reported pain can vary, and the patient's description of the history, symptoms, and discomfort might be different from one to another, not allowing a reliable and valid diagnosis. The dental practitioner, using a variety of diagnostic and measurement techniques each day, will often have difficulties in differentiating dentin hypersensitivity from

  3. Development and validation of a stability indicating HPTLC-densitometric method for lafutidine

    Directory of Open Access Journals (Sweden)

    Dinesh Dhamecha

    2013-01-01

    Full Text Available Background: A simple, selective, precise, and stability indicating high-performance thin layer chromatographic method has been established and validated for analysis of lafutidine in bulk drug and formulations. Materials and Methods: The compounds were analyzed on aluminum backed silica gel 60 F 254 plates with chloroform:ethanol:acetic Acid (8:1:1 as mobile phase. Densitometric analysis of lafutidine was performed at 230 nm. Result : Regression analysis data for the calibration plots were indicative of good linear relationship between response and concentration over the range 100-500 ng per spot. The correlation coefficient (r 2 was 0.998±0.002. Conclusion: Lafutidine was subjected to acid, base, peroxide, and sunlight degradation. In stability tests, the drug was susceptible to acid and basic hydrolysis, oxidation, and photodegradation.

  4. A simple method for validation and verification of pipettes mounted on automated liquid handlers

    DEFF Research Database (Denmark)

    Stangegaard, Michael; Hansen, Anders Johannes; Frøslev, Tobias Guldberg

    plate (BD Falcon) manually by means of calibrated pipettes. Each pipette of the liquid handler (1 up to 8) dispensed a selected volume (1 to 200µl) of Orange G 8 times into the wells of the microtiter plate. All wells contained a total of 200µL liquid. The optical density (OD) was read at 490 nm...... We have implemented a simple method for validation and verification of the performance of pipettes mounted on automated liquid handlers as necessary for laboratories accredited under ISO 17025. An 8-step serial dilution of Orange G was prepared in quadruplicates in a flat bottom 96-well microtiter...... pipettes were either repaired or the volume deviation was compensated for by applying a calibration curve in the liquid handler software. We have implemented the method on a Sias Xantus, an MWGt TheONYX, three Tecan Freedom EVO, a Biomek NX Span-8 and four Biomek 3000 robots, and the scripts are freely...

  5. Multicenter validation of PCR-based method for detection of Salmonella in chicken and pig samples

    DEFF Research Database (Denmark)

    Malorny, B.; Cook, N.; D'Agostino, M.

    2004-01-01

    As part of a standardization project, an interlaboratory trial including 15 laboratories from 13 European countries was conducted to evaluate the performance of a noproprietary polymerase chain reaction (PCR)-based method for the detection of Salmonella on artificially contaminated chicken rinse......) and PCR assay (gel electrophoresis detection) were performed by the receiving laboratories. Aliquots of BPW enrichment cultures were sent to the participants, who analyzed them using a thermal lysis procedure followed by a validated Salmonella-specific PCR assay. The results were reported as negative...... specificity was 80.1% (with 85.7% accordance and 67.5% concordance) for chicken rinse, and 91.7% (with 100% accordance and 83.3% concordance) for pig swab. Thus, the interlaboratory variation due to personnel, reagents, thermal cyclers, etc., did not affect the performance of the method, which...

  6. Validation of the activity expansion method with ultrahigh pressure shock equations of state

    Energy Technology Data Exchange (ETDEWEB)

    Rogers, F.J.; Young, D.A. [Physics Department, Lawrence Livermore National Laboratory, P.O. Box 808, Livermore, California 94550 (United States)

    1997-11-01

    Laser shock experiments have recently been used to measure the equation of state (EOS) of matter in the ultrahigh pressure region between condensed matter and a weakly coupled plasma. Some ultrahigh pressure data from nuclear-generated shocks are also available. Matter at these conditions has proven very difficult to treat theoretically. The many-body activity expansion method (ACTEX) has been used for some time to calculate EOS and opacity data in this region, for use in modeling inertial confinement fusion and stellar interior plasmas. In the present work, we carry out a detailed comparison with the available experimental data in order to validate the method. The agreement is good, showing that ACTEX adequately describes strongly shocked matter. {copyright} {ital 1997} {ital The American Physical Society}

  7. Validation of the activity expansion method with ultrahigh pressure shock equations of state

    Science.gov (United States)

    Rogers, Forrest J.; Young, David A.

    1997-11-01

    Laser shock experiments have recently been used to measure the equation of state (EOS) of matter in the ultrahigh pressure region between condensed matter and a weakly coupled plasma. Some ultrahigh pressure data from nuclear-generated shocks are also available. Matter at these conditions has proven very difficult to treat theoretically. The many-body activity expansion method (ACTEX) has been used for some time to calculate EOS and opacity data in this region, for use in modeling inertial confinement fusion and stellar interior plasmas. In the present work, we carry out a detailed comparison with the available experimental data in order to validate the method. The agreement is good, showing that ACTEX adequately describes strongly shocked matter.

  8. Validation of MIMGO: a method to identify differentially expressed GO terms in a microarray dataset

    Directory of Open Access Journals (Sweden)

    Yamada Yoichi

    2012-12-01

    Full Text Available Abstract Background We previously proposed an algorithm for the identification of GO terms that commonly annotate genes whose expression is upregulated or downregulated in some microarray data compared with in other microarray data. We call these “differentially expressed GO terms” and have named the algorithm “matrix-assisted identification method of differentially expressed GO terms” (MIMGO. MIMGO can also identify microarray data in which genes annotated with a differentially expressed GO term are upregulated or downregulated. However, MIMGO has not yet been validated on a real microarray dataset using all available GO terms. Findings We combined Gene Set Enrichment Analysis (GSEA with MIMGO to identify differentially expressed GO terms in a yeast cell cycle microarray dataset. GSEA followed by MIMGO (GSEA + MIMGO correctly identified (p Conclusions MIMGO is a reliable method to identify differentially expressed GO terms comprehensively.

  9. Development and validation of a dissolution method for warfarin sodium and aspirin combination tablets.

    Science.gov (United States)

    McCormick, T J; Gibson, A B; Diana, F J

    1997-08-01

    A dissolution method for warfarin sodium-aspirin combination tablets was developed which utilizes USP Apparatus 1 (baskets) at 50 rpm with 900 ml of phosphate buffer (pH 6.8; 0.05 M) medium at 37 degrees C. A reversed-phase liquid chromatographic method was also developed for the simultaneous determination of warfarin sodium, aspirin and salicylic acid on an octadecylsilica column using acetonitrile-tetrahydrofuran-glacial acetic acid-water (23:5:5:67, v/v/v/v) as the mobile phase with UV detection at 282 nm. Validation data were obtained which demonstrate that the dissolution methodology is accurate, precise, linear and rugged for the combination tablets.

  10. Characterization and validation of sampling and analytical methods for mycotoxins in workplace air.

    Science.gov (United States)

    Jargot, Danièle; Melin, Sandrine

    2013-03-01

    Mycotoxins are produced by certain plant or foodstuff moulds under growing, transport or storage conditions. They are toxic for humans and animals, some are carcinogenic. Methods to monitor occupational exposure to seven of the most frequently occurring airborne mycotoxins have been characterized and validated. Experimental aerosols have been generated from naturally contaminated particles for sampler evaluation. Air samples were collected on foam pads, using the CIP 10 personal aerosol sampler with its inhalable health-related aerosol fraction selector. The samples were subsequently solvent extracted from the sampling media, cleaned using immunoaffinity (IA) columns and analyzed by liquid chromatography with fluorescence detection. Ochratoxin A (OTA) or fumonisin and aflatoxin derivatives were detected and quantified. The quantification limits were 0.015 ng m(-3) OTA, 1 ng m(-3) fumonisins or 0.5 pg m(-3) aflatoxins, with a minimum dust concentration level of 1 mg m(-3) and a 4800 L air volume sampling. The methods were successfully applied to field measurements, which confirmed that workers could be exposed when handling contaminated materials. It was observed that airborne particles may be more contaminated than the bulk material itself. The validated methods have measuring ranges fully adapted to the concentrations found in the workplace. Their performance meets the general requirements laid down for chemical agent measurement procedures, with an expanded uncertainty less than 50% for most mycotoxins. The analytical uncertainty, comprised between 14 and 24%, was quite satisfactory given the low mycotoxin amounts, when compared to the food benchmarks. The methods are now user-friendly enough to be adopted for personal workplace sampling. They will later allow for mycotoxin occupational risk assessment, as only very few quantitative data have been available till now.

  11. DEVELOPMENT AND VALIDATION OF NUMERICAL METHOD FOR STRENGTH ANALYSIS OF LATTICE COMPOSITE FUSELAGE STRUCTURES

    Directory of Open Access Journals (Sweden)

    2016-01-01

    Full Text Available Lattice composite fuselage structures are developed as an alternative to conventional composite structures based on laminated skin and stiffeners. Structure layout of lattice structures allows to realize advantages of current composite materials to a maximal extent, at the same time minimizing their main shortcomings, that allows to provide higher weight efficiency for these structures in comparison with conventional analogues.Development and creation of lattice composite structures requires development of novel methods of strength anal- ysis, as conventional methods, as a rule, are aiming to strength analysis of thin-walled elements and do not allow to get confident estimation of local strength of high-loaded unidirectional composite ribs.In the present work the method of operative strength analysis of lattice composite structure is presented, based onspecialized FE-models of unidirectional composite ribs and their intersections. In the frames of the method, every rib is modeled by a caisson structure, consisting of arbitrary number of flanges and webs, modeled by membrane finite elements. Parameters of flanges and webs are calculated automatically from the condition of stiffness characteristics equality of real rib and the model. This method allows to perform local strength analysis of high-loaded ribs of lattice structure without use of here-dimensional finite elements, that allows to shorten time of calculations and sufficiently simplify the procedure of analysis of results of calculations.For validation of the suggested method, the results of experimental investigations of full-scale prototype of shell of lattice composite fuselage section have been used. The prototype of the lattice section was manufactured in CRISM and tested in TsAGI within the frames of a number of Russian and International scientific projects. The results of validation have shown that the suggested method allows to provide high operability of strength analysis, keeping

  12. Validation of analytical methods for the quality control of Naproxen suppositories

    International Nuclear Information System (INIS)

    Rodriguez Hernandez, Yaslenis; Suarez Perez, Yania; Garcia Pulpeiro, Oscar; Hernandez Contreras, Orestes Yuniel

    2011-01-01

    The analysis methods that will be used for the quality control of the future Cuban-made Naproxen suppositories for adults and children were developed for the first time in this paper. One method based on direct ultraviolet spectrophotometry was put forward, which proved to be specific, linear, accurate and precise for the quality control of Naproxen suppositories, taking into account the presence of chromophore groups in their structure. Likewise, the direct semi-aqueous acid-base volumetry method aimed at the quality control of the Naproxen raw material was changed and adapted to the quality control of suppositories. On the basis of the validation process, there was demonstrated the adequate specificity of this method with respect to the formulation components, as well as its linearity, accuracy and precision in 1-3 mg/ml range. The final results were compared and no significant statistical differences among the replicas per each dose were found in both methods; therefore, both may be used in the quality control of Naproxen suppositories

  13. [Development and validation of event-specific quantitative PCR method for genetically modified maize LY038].

    Science.gov (United States)

    Mano, Junichi; Masubuchi, Tomoko; Hatano, Shuko; Futo, Satoshi; Koiwa, Tomohiro; Minegishi, Yasutaka; Noguchi, Akio; Kondo, Kazunari; Akiyama, Hiroshi; Teshima, Reiko; Kurashima, Takeyo; Takabatake, Reona; Kitta, Kazumi

    2013-01-01

    In this article, we report a novel real-time PCR-based analytical method for quantitation of the GM maize event LY038. We designed LY038-specific and maize endogenous reference DNA-specific PCR amplifications. After confirming the specificity and linearity of the LY038-specific PCR amplification, we determined the conversion factor required to calculate the weight-based content of GM organism (GMO) in a multilaboratory evaluation. Finally, in order to validate the developed method, an interlaboratory collaborative trial according to the internationally harmonized guidelines was performed with blind DNA samples containing LY038 at the mixing levels of 0, 0.5, 1.0, 5.0 and 10.0%. The precision of the method was evaluated as the RSD of reproducibility (RSDR), and the values obtained were all less than 25%. The limit of quantitation of the method was judged to be 0.5% based on the definition of ISO 24276 guideline. The results from the collaborative trial suggested that the developed quantitative method would be suitable for practical testing of LY038 maize.

  14. Optimization and Validation of Quantitative Spectrophotometric Methods for the Determination of Alfuzosin in Pharmaceutical Formulations

    Directory of Open Access Journals (Sweden)

    M. Vamsi Krishna

    2007-01-01

    Full Text Available Three accurate, simple and precise spectrophotometric methods for the determination of alfuzosin hydrochloride in bulk drugs and tablets are developed. The first method is based on the reaction of alfuzosin with ninhydrin reagent in N, N'-dimethylformamide medium (DMF producing a colored product which absorbs maximally at 575 nm. Beer’s law is obeyed in the concentration range 12.5-62.5 µg/mL of alfuzosin. The second method is based on the reaction of drug with ascorbic acid in DMF medium resulting in the formation of a colored product, which absorbs maximally at 530 nm. Beer’s law is obeyed in the concentration 10-50 µg/mL of alfuzosin. The third method is based on the reaction of alfuzosin with p-benzoquinone (PBQ to form a colored product with λmax at 400 nm. The products of the reaction were stable for 2 h at room temperature. The optimum experimental parameters for the reactions have been studied. The validity of the described procedures was assessed. Statistical analysis of the results has been carried out revealing high accuracy and good precision. The proposed methods could be used for the determination of alfuzosin in pharmaceutical formulations. The procedures were rapid, simple and suitable for quality control application.

  15. A validated stability-indicating UPLC method for desloratadine and its impurities in pharmaceutical dosage forms.

    Science.gov (United States)

    Rao, Dantu Durga; Satyanarayana, N V; Malleswara Reddy, A; Sait, Shakil S; Chakole, Dinesh; Mukkanti, K

    2010-02-05

    A novel stability-indicating gradient reverse phase ultra-performance liquid chromatographic (RP-UPLC) method was developed for the determination of purity of desloratadine in presence of its impurities and forced degradation products. The method was developed using Waters Aquity BEH C18 column with mobile phase containing a gradient mixture of solvents A and B. The eluted compounds were monitored at 280nm. The run time was 8min within which desloratadine and its five impurities were well separated. Desloratadine was subjected to the stress conditions of oxidative, acid, base, hydrolytic, thermal and photolytic degradation. Desloratadine was found to degrade significantly in oxidative and thermal stress conditions and stable in acid, base, hydrolytic and photolytic degradation conditions. The degradation products were well resolved from main peak and its impurities, thus proved the stability-indicating power of the method. The developed method was validated as per ICH guidelines with respect to specificity, linearity, limit of detection, limit of quantification, accuracy, precision and robustness. This method was also suitable for the assay determination of desloratadine in pharmaceutical dosage forms.

  16. Testing and validation of methods for the diagnosis and recomendation integrated system for Signal grass

    Directory of Open Access Journals (Sweden)

    Silveira Cristiane Prezotto

    2005-01-01

    Full Text Available The Diagnosis and Recommendation Integrated System (DRIS allows the interpretation of results of leaf analysis through relationships among nutrients, instead of the absolute and isolated concentration of each one, as it is used by the criterion of sufficiency range. The objective was to evaluate three procedures of calculation of DRIS indices, and to verify the efficiency of DRIS as interpretation method for the results of Brachiaria decumbens (Signal grass. The study was developed with the results of six experiments carried out in a greenhouse at Piracicaba, SP, with nutrient solution. Concentrations of N, P, K, Ca, Mg, S, Cu, Fe, Mn, and Zn were used in the samples of recently expanded leaf laminae of the grass. The validation of the DRIS method used results from an experiment with nitrogen and sulfur rates applied to the same grass from the Mundo Novo farm, Brotas, SP. DRIS indices were calculated according to two criteria to choose the ratio order of nutrients (F value and R value and three ways to calculate the nutrient functions (methods of Beaufils, Jones, and Elwali & Gascho. Nutritional Balance Index (NBI, calculated according to the generated norms, presented negative and significant correlation coefficients with the productivity in the combinations of methods tested and DRIS methods proposed by Beaufils, Jones and Elwali & Gascho were efficient in detecting concentrations that show nutrients deficiency or excess.

  17. European validation of Real-Time PCR method for detection of Salmonella spp. in pork meat.

    Science.gov (United States)

    Delibato, Elisabetta; Rodriguez-Lazaro, David; Gianfranceschi, Monica; De Cesare, Alessandra; Comin, Damiano; Gattuso, Antonietta; Hernandez, Marta; Sonnessa, Michele; Pasquali, Frédérique; Sreter-Lancz, Zuzsanna; Saiz-Abajo, María-José; Pérez-De-Juan, Javier; Butrón, Javier; Prukner-Radovcic, Estella; Horvatek Tomic, Danijela; Johannessen, Gro S; Jakočiūnė, Džiuginta; Olsen, John E; Chemaly, Marianne; Le Gall, Francoise; González-García, Patricia; Lettini, Antonia Anna; Lukac, Maja; Quesne, Segolénè; Zampieron, Claudia; De Santis, Paola; Lovari, Sarah; Bertasi, Barbara; Pavoni, Enrico; Proroga, Yolande T R; Capuano, Federico; Manfreda, Gerardo; De Medici, Dario

    2014-08-01

    The classical microbiological method for detection of Salmonella spp. requires more than five days for final confirmation, and consequently there is a need for an alternative methodology for detection of this pathogen particularly in those food categories with a short shelf-life. This study presents an international (at European level) ISO 16140-based validation study of a non-proprietary Real-Time PCR-based method that can generate final results the day following sample analysis. It is based on an ISO compatible enrichment coupled to an easy and inexpensive DNA extraction and a consolidated Real-Time PCR assay. Thirteen laboratories from seven European Countries participated to this trial, and pork meat was selected as food model. The limit of detection observed was down to 10 CFU per 25 g of sample, showing excellent concordance and accordance values between samples and laboratories (100%). In addition, excellent values were obtained for relative accuracy, specificity and sensitivity (100%) when the results obtained for the Real-Time PCR-based methods were compared to those of the ISO 6579:2002 standard method. The results of this international trial demonstrate that the evaluated Real-Time PCR-based method represents an excellent alternative to the ISO standard. In fact, it shows an equal and solid performance as well as it reduces dramatically the extent of the analytical process, and can be easily implemented routinely by the Competent Authorities and Food Industry laboratories. Copyright © 2014 Elsevier B.V. All rights reserved.

  18. Method validation to determine total alpha beta emitters in water samples using LSC

    International Nuclear Information System (INIS)

    Al-Masri, M. S.; Nashawati, A.; Al-akel, B.; Saaid, S.

    2006-06-01

    In this work a method was validated to determine gross alpha and beta emitters in water samples using liquid scintillation counter. 200 ml of water from each sample were evaporated to 20 ml and 8 ml of them were mixed with 12 ml of the suitable cocktail to be measured by liquid scintillation counter Wallac Winspectral 1414. The lower detection limit by this method (LDL) was 0.33 DPM for total alpha emitters and 1.3 DPM for total beta emitters. and the reproducibility limit was (± 2.32 DPM) and (±1.41 DPM) for total alpha and beta emitters respectively, and the repeatability limit was (±2.19 DPM) and (±1.11 DPM) for total alpha and beta emitters respectively. The method is easy and fast because of the simple preparation steps and the large number of samples that can be measured at the same time. In addition, many real samples and standard samples were analyzed by the method and showed accurate results so it was concluded that the method can be used with various water samples. (author)

  19. Analytical Quality by Design Approach to Test Method Development and Validation in Drug Substance Manufacturing

    Directory of Open Access Journals (Sweden)

    N. V. V. S. S. Raman

    2015-01-01

    Full Text Available Pharmaceutical industry has been emerging rapidly for the last decade by focusing on product Quality, Safety, and Efficacy. Pharmaceutical firms increased the number of product development by using scientific tools such as QbD (Quality by Design and PAT (Process Analytical Technology. ICH guidelines Q8 to Q11 have discussed QbD implementation in API synthetic process and formulation development. ICH Q11 guidelines clearly discussed QbD approach for API synthesis with examples. Generic companies are implementing QbD approach in formulation development and even it is mandatory for USFDA perspective. As of now there is no specific requirements for AQbD (Analytical Quality by Design and PAT in analytical development from all regulatory agencies. In this review, authors have discussed the implementation of QbD and AQbD simultaneously for API synthetic process and analytical methods development. AQbD key tools are identification of ATP (Analytical Target Profile, CQA (Critical Quality Attributes with risk assessment, Method Optimization and Development with DoE, MODR (method operable design region, Control Strategy, AQbD Method Validation, and Continuous Method Monitoring (CMM. Simultaneous implementation of QbD activities in synthetic and analytical development will provide the highest quality product by minimizing the risks and even it is very good input for PAT approach.

  20. Validation of CT brain perfusion methods using a realistic dynamic head phantom.

    Science.gov (United States)

    Riordan, Alan J; Prokop, Mathias; Viergever, Max A; Dankbaar, Jan Willem; Smit, Ewoud J; de Jong, Hugo W A M

    2011-06-01

    Development and evaluation of a realistic hybrid head phantom for the validation of quantitative CT brain perfusion methods. A combination, or hybrid, of CT images of an anthropomorphic head phantom together with clinically acquired MRI brain images was used to construct a dynamic hybrid head phantom. Essential CT imaging parameters such as spatially dependent noise, effects of resolution, tube settings, and reconstruction parameters were intrinsically included by scanning a skull phantom using CT perfusion (CTP) protocols with varying mAs. These data were combined with processed high resolution 7T clinical MRI images to include healthy and diseased brain parenchyma, as well as the cerebral vascular system. Time attenuation curves emulating contrast bolus passage based on perfusion as observed in clinical studies were added. Using the phantom, CTP images were generated using three brain perfusion calculation methods: bcSVD, sSVD, and fit-based deconvolution, and the linearity and accuracy of the three calculation methods was assessed. Dependency of perfusion outcome on calculation method was compared to clinical data. Furthermore, the potential of the phantom to optimize brain perfusion packages was investigated. All perfusion calculation methods showed overestimation of low perfusion values and underestimation of high perfusion values. Good correlation in behavior between phantom and clinical data was found (R2 = 0.84). A dynamic hybrid head phantom constructed from CT and MRI data was demonstrated to realistically represent clinical CTP studies, which is useful for assessing CT brain perfusion acquisition, reconstruction, and analysis.

  1. Proposal for Requirement Validation Criteria and Method Based on Actor Interaction

    Science.gov (United States)

    Hattori, Noboru; Yamamoto, Shuichiro; Ajisaka, Tsuneo; Kitani, Tsuyoshi

    We propose requirement validation criteria and a method based on the interaction between actors in an information system. We focus on the cyclical transitions of one actor's situation against another and clarify observable stimuli and responses based on these transitions. Both actors' situations can be listed in a state transition table, which describes the observable stimuli or responses they send or receive. Examination of the interaction between both actors in the state transition tables enables us to detect missing or defective observable stimuli or responses. Typically, this method can be applied to the examination of the interaction between a resource managed by the information system and its user. As a case study, we analyzed 332 requirement defect reports of an actual system development project in Japan. We found that there were a certain amount of defects regarding missing or defective stimuli and responses, which can be detected using our proposed method if this method is used in the requirement definition phase. This means that we can reach a more complete requirement definition with our proposed method.

  2. Development and validation of a simplified titration method for monitoring volatile fatty acids in anaerobic digestion.

    Science.gov (United States)

    Sun, Hao; Guo, Jianbin; Wu, Shubiao; Liu, Fang; Dong, Renjie

    2017-09-01

    The volatile fatty acids (VFAs) concentration has been considered as one of the most sensitive process performance indicators in anaerobic digestion (AD) process. However, the accurate determination of VFAs concentration in AD processes normally requires advanced equipment and complex pretreatment procedures. A simplified method with fewer sample pretreatment procedures and improved accuracy is greatly needed, particularly for on-site application. This report outlines improvements to the Nordmann method, one of the most popular titrations used for VFA monitoring. The influence of ion and solid interfering subsystems in titrated samples on results accuracy was discussed. The total solid content in titrated samples was the main factor affecting accuracy in VFA monitoring. Moreover, a high linear correlation was established between the total solids contents and VFA measurement differences between the traditional Nordmann equation and gas chromatography (GC). Accordingly, a simplified titration method was developed and validated using a semi-continuous experiment of chicken manure anaerobic digestion with various organic loading rates. The good fitting of the results obtained by this method in comparison with GC results strongly supported the potential application of this method to VFA monitoring. Copyright © 2017. Published by Elsevier Ltd.

  3. Convergent validity of a novel method for quantifying rowing training loads.

    Science.gov (United States)

    Tran, Jacqueline; Rice, Anthony J; Main, Luana C; Gastin, Paul B

    2015-01-01

    Elite rowers complete rowing-specific and non-specific training, incorporating continuous and interval-like efforts spanning the intensity spectrum. However, established training load measures are unsuitable for use in some modes and intensities. Consequently, a new measure known as the T2minute method was created. The method quantifies load as the time spent in a range of training zones (time-in-zone), multiplied by intensity- and mode-specific weighting factors that scale the relative stress of different intensities and modes to the demands of on-water rowing. The purpose of this study was to examine the convergent validity of the T2minute method with Banister's training impulse (TRIMP), Lucia's TRIMP and Session-RPE when quantifying elite rowing training. Fourteen elite rowers (12 males, 2 females) were monitored during four weeks of routine training. Unadjusted T2minute loads (using coaches' estimates of time-in-zone) demonstrated moderate-to-strong correlations with Banister's TRIMP, Lucia's TRIMP and Session-RPE (rho: 0.58, 0.55 and 0.42, respectively). Adjusting T2minute loads by using actual time-in-zone data resulted in stronger correlations between the T2minute method and Banister's TRIMP and Lucia's TRIMP (rho: 0.85 and 0.81, respectively). The T2minute method is an appropriate in-field measure of elite rowing training loads, particularly when actual time-in-zone values are used to quantify load.

  4. Validation of nitrogen-nitrate analysis by the chromotropic acid method

    Energy Technology Data Exchange (ETDEWEB)

    Santos, Ana Claudia O.; Matoso, Erika, E-mail: anaclaudia.oliveira@marinha.mil.br [Centro Tecnológico da Marinha em São Paulo (CTMSP/CEA), Iperó, SP (Brazil). Centro Experimental ARAMAR

    2017-07-01

    The problems caused by contamination of water bodies demand strict control of disposal in rivers, seas and oceans. Nitrate ion is present in agricultural inputs, which are applied to the soil to boost plant growth. However, excess or indiscriminate use of these products contaminates water bodies, triggering eutrophication of the aquatic ecosystems. Furthermore, due to diseases that can be caused by the ingestion of high levels of nitrate, such as methaemoglobinaemia, nitrate levels should be controlled in drinking waters and effluents. There are several methods for the determination of nitrate, being the chromotropic acid method a simple and low-cost solution. This method consists of acid addition into the sample in the presence of H{sub 2}SO{sub 4}. The absorbance related to the produced yellow color can be measured by a UV-Vis spectrophotometer at 410 nm. In a modified form, this method can be applied to different aqueous matrices by use of other reagents that eliminate interferences. The aim of this study was to validate the nitrate determination method in waters using chromotropic acid. This method is used in Laboratório Radioecológico (LARE) to analyze effluent to comply with Wastewater Controlling Program of Centro Tecnológico da Marinha em São Paulo – Centro Experimental ARAMAR (CTMSP-CEA). The correlation coefficient for the linearity test was 0.9997. The evaluated detection limit was relatively high (LD = 0.045 mgN/L), if compared to ion chromatography, for example, but enough to determine the presence of this ion, considering the maximum limit proposed by the current legislation. The chromotropic acid method showed to be a robust, accurate and precise method, according the parameters used in this work. (author)

  5. Validation of nitrogen-nitrate analysis by the chromotropic acid method

    International Nuclear Information System (INIS)

    Santos, Ana Claudia O.; Matoso, Erika

    2017-01-01

    The problems caused by contamination of water bodies demand strict control of disposal in rivers, seas and oceans. Nitrate ion is present in agricultural inputs, which are applied to the soil to boost plant growth. However, excess or indiscriminate use of these products contaminates water bodies, triggering eutrophication of the aquatic ecosystems. Furthermore, due to diseases that can be caused by the ingestion of high levels of nitrate, such as methaemoglobinaemia, nitrate levels should be controlled in drinking waters and effluents. There are several methods for the determination of nitrate, being the chromotropic acid method a simple and low-cost solution. This method consists of acid addition into the sample in the presence of H 2 SO 4 . The absorbance related to the produced yellow color can be measured by a UV-Vis spectrophotometer at 410 nm. In a modified form, this method can be applied to different aqueous matrices by use of other reagents that eliminate interferences. The aim of this study was to validate the nitrate determination method in waters using chromotropic acid. This method is used in Laboratório Radioecológico (LARE) to analyze effluent to comply with Wastewater Controlling Program of Centro Tecnológico da Marinha em São Paulo – Centro Experimental ARAMAR (CTMSP-CEA). The correlation coefficient for the linearity test was 0.9997. The evaluated detection limit was relatively high (LD = 0.045 mgN/L), if compared to ion chromatography, for example, but enough to determine the presence of this ion, considering the maximum limit proposed by the current legislation. The chromotropic acid method showed to be a robust, accurate and precise method, according the parameters used in this work. (author)

  6. VALIDATION OF ANALYTICAL METHODS AND INSTRUMENTATION FOR BERYLLIUM MEASUREMENT: REVIEW AND SUMMARY OF AVAILABLE GUIDES, PROCEDURES, AND PROTOCOLS

    Energy Technology Data Exchange (ETDEWEB)

    Ekechukwu, A.

    2008-12-17

    This document proposes to provide a listing of available sources which can be used to validate analytical methods and/or instrumentation for beryllium determination. A literature review was conducted of available standard methods and publications used for method validation and/or quality control. A comprehensive listing of the articles, papers, and books reviewed is given in Appendix 1. Available validation documents and guides are listed in the appendix; each has a brief description of application and use. In the referenced sources, there are varying approaches to validation and varying descriptions of validation at different stages in method development. This discussion focuses on validation and verification of fully developed methods and instrumentation that have been offered up for use or approval by other laboratories or official consensus bodies such as ASTM International, the International Standards Organization (ISO) and the Association of Official Analytical Chemists (AOAC). This review was conducted as part of a collaborative effort to investigate and improve the state of validation for measuring beryllium in the workplace and the environment. Documents and publications from the United States and Europe are included. Unless otherwise specified, all documents were published in English.

  7. Validation of a photography-based goniometry method for measuring joint range of motion.

    Science.gov (United States)

    Blonna, Davide; Zarkadas, Peter C; Fitzsimmons, James S; O'Driscoll, Shawn W

    2012-01-01

    A critical component of evaluating the outcomes after surgery to restore lost elbow motion is the range of motion (ROM) of the elbow. This study examined if digital photography-based goniometry is as accurate and reliable as clinical goniometry for measuring elbow ROM. Instrument validity and reliability for photography-based goniometry were evaluated for a consecutive series of 50 elbow contractures by 4 observers with different levels of elbow experience. Goniometric ROM measurements were taken with the elbows in full extension and full flexion directly in the clinic (once) and from digital photographs (twice in a blinded random manner). Instrument validity for photography-based goniometry was extremely high (intraclass correlation coefficient: extension = 0.98, flexion = 0.96). For extension and flexion measurements by the expert surgeon, systematic error was negligible (0° and 1°, respectively). Limits of agreement were 7° (95% confidence interval [CI], 5° to 9°) and -7° (95% CI, -5° to -9°) for extension and 8° (95% CI, 6° to 10°) and -7° (95% CI, -5° to -9°) for flexion. Interobserver reliability for photography-based goniometry was better than that for clinical goniometry. The least experienced observer's photographic goniometry measurements were closer to the reference measurements than the clinical goniometry measurements. Photography-based goniometry is accurate and reliable for measuring elbow ROM. The photography-based method relied less on observer expertise than clinical goniometry. This validates an objective measure of patient outcome without requiring doctor-patient contact at a tertiary care center, where most contracture surgeries are done. Copyright © 2012 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Mosby, Inc. All rights reserved.

  8. Determination of bacterial endotoxin (pyrogen) in radiopharmaceuticals by the gel clot method. Validation

    International Nuclear Information System (INIS)

    Fukumori, Neuza Taeko Okasaki

    2008-01-01

    Before the Limulus amebocyte lysate (LAL) test, the only available means of pirogenicity testing for parenteral drugs and medical devices was the United States Pharmacopoeia (USP) rabbit pyrogen test. Especially for radiopharmaceuticals, the LAL assay is the elective way to determine bacterial endotoxin. The aim of this work was to validate the gel clot method for some radiopharmaceuticals without measurable interference. The FDA's LALTest guideline defines interference as a condition that causes a significant difference between the endpoints of a positive water control and positive product control series using a standard endotoxin. Experiments were performed in accordance to the USP bacterial endotoxins test in the 131 I- m-iodobenzylguanidine; the radioisotopes Gallium-67 and Thallium-201; the lyophilized reagents DTPA, Phytate, GHA, HSA and Colloidal Tin. The Maximum Valid Dilution (MVD) was calculated for each product based upon the clinical dose of the material and a twofold serial dilution below the MVD was performed in duplicate to detect interferences. The labeled sensitivity of the used LAL reagent was 0.125 EU mL -1 (Endotoxin Units per milliliter). For validation, a dilution series was performed, a twofold dilution of control standard endotoxin (CSE) from 0.5 to 0.03 EU mL -1 , to confirm the labeled sensitivity of the LAL reagent being tested in sterile and non pyrogenic water, in quadruplicate. The same dilution series was performed with the CSE and the product in the 1:100 dilution factor, in three consecutive batches of each radiopharmaceutical. The products 131 I-m-iodobenzylguanidine, Gallium-67, Thallium-201, DTPA, HSA and Colloidal Tin were found compatible with the LAL test at a 1:100 dilution factor. Phytate and GHA showed some interference in the gel clot test. Other techniques to determine endotoxins as the chromogenic (color development) and the turbidimetric test (turbidity development), were also assessed to get valuable quantitative and

  9. Using method triangulation to validate a new instrument (CPWQ-com) assessing cancer patients' satisfaction with communication

    DEFF Research Database (Denmark)

    Ross, Lone; Lundstrøm, Louise Hyldborg; Petersen, Morten Aagaard

    2012-01-01

    Patients' perceptions of care including the communication with health care staff is recognized as an important aspect of the quality of cancer care. Using mixed methods, we developed and validated a short instrument assessing this communication....

  10. Validation of analytical method to calculate the concentration of conjugated monoclonal antibody

    International Nuclear Information System (INIS)

    Alcarde, Lais F.; Massicano, Adriana V.F.; Oliveira, Ricardo S.; Araujo, Elaine B. de

    2013-01-01

    The objective of this study was to develop a quantitative analytical method using high performance liquid chromatography (HPLC) to determine the antibody concentration in conjunction with bifunctional chelator. Assays were performed using a high performance liquid chromatograph, and the following conditions were used: flow rate of 1 mL / min, 15 min run time, 0.2 M sodium phosphate buffer pH 7.0 as the mobile phase and column of molecular exclusion BioSep SEC S-3000 (300 x 7.8 mm, 5 μM - Phenomenex). The calibration curve was obtained with AcM diluted in 0.2 M sodium phosphate buffer pH 7.0 by serial dilution, yielding the concentrations: 400 μg/mL, 200 μg/mL, 100 μg/mL, 50 μg/mL, 25 μg/mL and 12.5 μg/mL. From the calibration curve calculated the equation of the line and with it the concentration of the immunoconjugate. To ensure the validity of the method accuracy and precision studies were conducted. The accuracy test consisted in the evaluation of 3 samples of known concentration, being this test performed with low concentrations (50 μg/mL), medium (100 μg/mL) and high (200 μg/mL). The precision test consisted of 3 consecutive measurements of one sample of known concentration, subject to the conditions set forth above for the other tests. The correlation coefficient of the standard curve was greater than 97%, the accuracy was satisfactory at low concentrations as well as accuracy. The method was validated by showing it for the accurate and precise determination of the concentration of the immunoconjugate. Furthermore, this assay was found to be extremely important, because using the correct mass of the protein, the radiochemical purity of the radioimmunoconjugate was above 95% in all studies

  11. Evaluation of bone formation in calcium phosphate scaffolds with μCT-method validation using SEM.

    Science.gov (United States)

    Lewin, S; Barba, A; Persson, C; Franch, J; Ginebra, M-P; Öhman-Mägi, C

    2017-10-05

    There is a plethora of calcium phosphate (CaP) scaffolds used as synthetic substitutes to bone grafts. The scaffold performance is often evaluated from the quantity of bone formed within or in direct contact with the scaffold. Micro-computed tomography (μCT) allows three-dimensional evaluation of bone formation inside scaffolds. However, the almost identical x-ray attenuation of CaP and bone obtrude the separation of these phases in μCT images. Commonly, segmentation of bone in μCT images is based on gray scale intensity, with manually determined global thresholds. However, image analysis methods, and methods for manual thresholding in particular, lack standardization and may consequently suffer from subjectivity. The aim of the present study was to provide a methodological framework for addressing these issues. Bone formation in two types of CaP scaffold architectures (foamed and robocast), obtained from a larger animal study (a 12 week canine animal model) was evaluated by μCT. In addition, cross-sectional scanning electron microscopy (SEM) images were acquired as references to determine thresholds and to validate the result. μCT datasets were registered to the corresponding SEM reference. Global thresholds were then determined by quantitatively correlating the different area fractions in the μCT image, towards the area fractions in the corresponding SEM image. For comparison, area fractions were also quantified using global thresholds determined manually by two different approaches. In the validation the manually determined thresholds resulted in large average errors in area fraction (up to 17%), whereas for the evaluation using SEM references, the errors were estimated to be less than 3%. Furthermore, it was found that basing the thresholds on one single SEM reference gave lower errors than determining them manually. This study provides an objective, robust and less error prone method to determine global thresholds for the evaluation of bone formation in

  12. Validated HPTLC methods for determination of some selected antihypertensive mixtures in their combined dosage forms

    Directory of Open Access Journals (Sweden)

    Rasha A. Shaalan

    2014-12-01

    Full Text Available Simple and selective HPTLC methods were developed for the simultaneous determination of the antihypertensive drugs; carvedilol and hydrochlorothiazide in their binary mixture (Mixture I and amlodipine besylate, valsartan, and hydrochlorothiazide in their combined ternary formulation (Mixture II. Effective chromatographic separation was achieved on Fluka TLC plates 20 × 20 cm aluminum cards, 0.2 mm thickness through linear ascending development. For Mixture I, the mobile phase composed of chloroform–methanol in the ratio 8:2 v/v. Detection was performed at 254 nm for both carvedilol and hydrochlorothiazide. For Mixture II, the mobile phase was chloroform–methanol–ammonia in the volume ratio 8:2:0.1. Detection was performed at 254 nm for valsartan and hydrochlorothiazide, and at 365 nm for amlodipine. Quantification was based on spectrodensitometric analysis. Analytical performance of the proposed HPTLC procedures was statistically validated with respect to linearity, ranges, precision, accuracy, specificity, robustness, detection and quantification limits. The linearity ranges were 0.05–1.0 and 0.1–2.0 μg/spot for carvedilol and hydrochlorothiazide, respectively in Mixture I, 0.1–2.0, 0.1–2.0 and 0.2–4.0 μg/spot for amlodipine, hydrochlorothiazide and valsartan, respectively in Mixture II, with correlation coefficients >0.9992. The validated HPTLC methods were applied to the analysis of the cited antihypertensive drugs in their combined pharmaceutical tablets. The proposed methods confirmed peak identity and purity.

  13. Validation of PCR methods for quantitation of genetically modified plants in food.

    Science.gov (United States)

    Hübner, P; Waiblinger, H U; Pietsch, K; Brodmann, P

    2001-01-01

    For enforcement of the recently introduced labeling threshold for genetically modified organisms (GMOs) in food ingredients, quantitative detection methods such as quantitative competitive (QC-PCR) and real-time PCR are applied by official food control laboratories. The experiences of 3 European food control laboratories in validating such methods were compared to describe realistic performance characteristics of quantitative PCR detection methods. The limit of quantitation (LOQ) of GMO-specific, real-time PCR was experimentally determined to reach 30-50 target molecules, which is close to theoretical prediction. Starting PCR with 200 ng genomic plant DNA, the LOQ depends primarily on the genome size of the target plant and ranges from 0.02% for rice to 0.7% for wheat. The precision of quantitative PCR detection methods, expressed as relative standard deviation (RSD), varied from 10 to 30%. Using Bt176 corn containing test samples and applying Bt176 specific QC-PCR, mean values deviated from true values by -7to 18%, with an average of 2+/-10%. Ruggedness of real-time PCR detection methods was assessed in an interlaboratory study analyzing commercial, homogeneous food samples. Roundup Ready soybean DNA contents were determined in the range of 0.3 to 36%, relative to soybean DNA, with RSDs of about 25%. Taking the precision of quantitative PCR detection methods into account, suitable sample plans and sample sizes for GMO analysis are suggested. Because quantitative GMO detection methods measure GMO contents of samples in relation to reference material (calibrants), high priority must be given to international agreements and standardization on certified reference materials.

  14. Validation of an HPLC method for the simultaneous determination of eletriptan and UK 120.413

    Directory of Open Access Journals (Sweden)

    LJILJANA ZIVANOVIC

    2006-11-01

    Full Text Available Arapid and sensitive RPHPLCmethod was developed for the routine control analysis of eletriptan hydrobromide and its organic impurity UK 120.413 in Relpax® tablets. The chromatography was performed at 20 °Cusing a C18 XTerraTM (5 m, 150 × 4,6 mm column at a flow rate 1.0 ml/min. The drug and its impurity were detected at 225 nm. The mobile phase consisted of TEA (1 % – methanol (67.2:32.8 v/v, the pH of which was adjusted to 6.8 with 85 % orthophosphoric acid. Quantification was accomplished by the internal standard method. The developed RP HPLC method was validated by testing: accuracy, precision, repeatibility, specificity, detection limit, quantification limit, linearity, robustness and sensitivity. High linearity of the analytical procedure was confirmed over the concentration range of 0.05 – 1.00 mg/ml for eletriptan hydrobromide and from 0.10 – 1.50 µg/ml for UK 120.413, with correlation coefficients greater than r = 0.995. The low value of the RSD expressed the good repeatability and precision of the method. Experimental design and a response surface method were used to test robustness of the analytical procedure and to evaluate the effect of variation of the method parameters, namely the mobile phase composition, pH and temperature. They showed small deviations from the method setting. The good recovery and low RSD confirm the suitability of the proposed RP HPLC method for the routine determination of eletriptan hydrobromide and its impurity UK 120.413 in Relpax® tables.

  15. Formulation and Development of a Validated UV-Spectrophotometric Analytical Method of Rutin Tablet

    Directory of Open Access Journals (Sweden)

    Murad N. Abualhasan

    2017-01-01

    Full Text Available Rutin is available in some foods, fruits, and vegetables. It has various beneficial medical effects making it useful in the treatment of various diseases. Rutin is available in different oral dosage forms such as tablets or capsules, widely available in the market. Rutin and many herbal medicines lack quality control due to unavailability of analytical methods. In this study, we formulated rutin tablet and studied its stability using a simple developed analytical method. The dissolution profile of our formulated tablet was also inspected. The results showed that our developed method was linear (R2=0.999, precise (% RSD = 0.026, and accurate (% recovery = 98.55–103.34. The formulated rutin tablet was stable under accelerated conditions as well as room temperature for 150 days (% assay > 91.69. The dissolution profile over 45 minutes of our formulated tablet showed a better dissolution (26.5% compared with the internationally marketed Rutin® tablet (18.5%. This study can serve as a guideline to companies that manufacture herbal products to improve their formulated herbs and apply validated analytical methods to check the quality of their product.

  16. New enantioselective LC method development and validation for the assay of modafinil.

    Science.gov (United States)

    Harvanová, Marianna; Gondová, Taťána

    2017-05-10

    For the first time, a new, fast and sensitive chromatographic method for the separation and determination of modafinil enantiomers was developed on chiral stationary phase with macrocyclic glycopeptide teicoplanin in the polar organic mode. The effect of the mobile phase composition and column temperature on the retention and enantioseparation were studied. The separation was performed using a Chirobiotic T column (250×4.6mm, 5μm) with methanol and triethylamine (100/0.05, v/v) as the mobile phase at a flow rate of 1.0mL/min, and UV detection at 225nm. The total analysis time is less than 6min, which is faster than the previous chiral HPLC methods (total run time of 12min). Calibration curves were linear (R 2 >0.999) over a concentration range 5-150μg/mL for each modafinil enantiomer. Limit of detection (LOD) and limit of quantification (LOQ) for (R)-modafinil were 15 and 45ng/mL and for (S)-modafinil were 20 and 60ng/mL, respectively. The recoveries were in the range of 100.5-102.3% with the relative standard deviations ranging from 0.4% to 1.0% for both enantiomers. It was demonstrated that the developed method was selective, precise and robust. The validated method was successfully applied for the separation and determination of modafinil enantiomers in the real samples. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Validation of MIMGO: a method to identify differentially expressed GO terms in a microarray dataset

    Science.gov (United States)

    2012-01-01

    Background We previously proposed an algorithm for the identification of GO terms that commonly annotate genes whose expression is upregulated or downregulated in some microarray data compared with in other microarray data. We call these “differentially expressed GO terms” and have named the algorithm “matrix-assisted identification method of differentially expressed GO terms” (MIMGO). MIMGO can also identify microarray data in which genes annotated with a differentially expressed GO term are upregulated or downregulated. However, MIMGO has not yet been validated on a real microarray dataset using all available GO terms. Findings We combined Gene Set Enrichment Analysis (GSEA) with MIMGO to identify differentially expressed GO terms in a yeast cell cycle microarray dataset. GSEA followed by MIMGO (GSEA + MIMGO) correctly identified (p microarray data in which genes annotated to differentially expressed GO terms are upregulated. We found that GSEA + MIMGO was slightly less effective than, or comparable to, GSEA (Pearson), a method that uses Pearson’s correlation as a metric, at detecting true differentially expressed GO terms. However, unlike other methods including GSEA (Pearson), GSEA + MIMGO can comprehensively identify the microarray data in which genes annotated with a differentially expressed GO term are upregulated or downregulated. Conclusions MIMGO is a reliable method to identify differentially expressed GO terms comprehensively. PMID:23232071

  18. Diagnostic Methods of Helicobacter pylori Infection for Epidemiological Studies: Critical Importance of Indirect Test Validation.

    Science.gov (United States)

    Miftahussurur, Muhammad; Yamaoka, Yoshio

    2016-01-01

    Among the methods developed to detect H. pylori infection, determining the gold standard remains debatable, especially for epidemiological studies. Due to the decreasing sensitivity of direct diagnostic tests (histopathology and/or immunohistochemistry [IHC], rapid urease test [RUT], and culture), several indirect tests, including antibody-based tests (serology and urine test), urea breath test (UBT), and stool antigen test (SAT) have been developed to diagnose H. pylori infection. Among the indirect tests, UBT and SAT became the best methods to determine active infection. While antibody-based tests, especially serology, are widely available and relatively sensitive, their specificity is low. Guidelines indicated that no single test can be considered as the gold standard for the diagnosis of H. pylori infection and that one should consider the method's advantages and disadvantages. Based on four epidemiological studies, culture and RUT present a sensitivity of 74.2-90.8% and 83.3-86.9% and a specificity of 97.7-98.8% and 95.1-97.2%, respectively, when using IHC as a gold standard. The sensitivity of serology is quite high, but that of the urine test was lower compared with that of the other methods. Thus, indirect test validation is important although some commercial kits propose universal cut-off values.

  19. Columbia River Stock Identification Study; Validation of Genetic Method, 1980-1981 Final Report.

    Energy Technology Data Exchange (ETDEWEB)

    Milner, George B.; Teel, David J.; Utter, Fred M. (Northwest and Alaska Fisheries Science Center, Coastal Zone and Estuarine Studies Division, Seattle, WA)

    1981-06-01

    The reliability of a method for obtaining maximum likelihood estimate of component stocks in mixed populations of salmonids through the frequency of genetic variants in a mixed population and in potentially contributing stocks was tested in 1980. A data base of 10 polymorphic loci from 14 hatchery stocks of spring chinook salmon of the Columbia River was used to estimate proportions of these stocks in four different blind'' mixtures whose true composition was only revealed subsequent to obtaining estimates. The accuracy and precision of these blind tests have validated the genetic method as a valuable means for identifying components of stock mixtures. Properties of the genetic method were further examined by simulation studies using the pooled data of the four blind tests as a mixed fishery. Replicated tests with samples sizes between 100 and 1,000 indicated that actual standard deviations on estimated contributions were consistently lower than calculated standard deviations; this difference diminished as sample size increased. It is recommended that future applications of the method be preceded by simulation studies that will identify appropriate levels of sampling required for acceptable levels of accuracy and precision. Variables in such studies include the stocks involved, the loci used, and the genetic differentiation among stocks. 8 refs., 6 figs., 4 tabs.

  20. Parallel Resolved Open Source CFD-DEM: Method, Validation and Application

    Directory of Open Access Journals (Sweden)

    A. Hager

    2014-03-01

    Full Text Available In the following paper the authors present a fully parallelized Open Source method for calculating the interaction of immersed bodies and surrounding fluid. A combination of computational fluid dynamics (CFD and a discrete element method (DEM accounts for the physics of both the fluid and the particles. The objects considered are relatively big compared to the cells of the fluid mesh, i.e. they cover several cells each. Thus this fictitious domain method (FDM is called resolved. The implementation is realized within the Open Source framework CFDEMcOupling (www.cfdem.com, which provides an interface between OpenFOAM® based CFD-solvers and the DEM software LIGGGHTS (www.liggghts.com. While both LIGGGHTS and OpenFOAM® were already parallelized, only a recent improvement of the algorithm permits the fully parallel computation of resolved problems. Alongside with a detailed description of the method, its implementation and recent improvements, a number of application and validation examples is presented in the scope of this paper.

  1. Optimized and Validated Spectrophotometric Methods for the Determination of Enalapril Maleate in Commercial Dosage Forms

    Directory of Open Access Journals (Sweden)

    Sk Manirul Haque

    2008-01-01

    Full Text Available Four simple, rapid and sensitive spectrophotometric methods have been proposed for the determination of enalapril maleate in pharmaceutical formulations. The first method is based on the reaction of carboxylic acid group of enalapril maleate with a mixture of potassium iodate (KIO3 and iodide (KI to form yellow colored product in aqueous medium at 25 ± 1°C .The reaction is followed spectrophotometrically by measuring the absorbance at 352 nm. The second, third and fourth methods are based on the charge transfer complexation reaction of the drug with p-chloranilic acid (pCA in 1, 4-dioxan-methanol medium, 2, 3-dichloro 5, 6-dicyano 1, 4-benzoquinone (DDQ in acetonitrile-1,4 dioxane medium and iodine in acetonitrile-dichloromethane medium. Under optimized experimental conditions, Beer’s law is obeyed in the concentration ranges of 2.5–50, 20–560, 5–75 and 10–200 μg mL−1, respectively. All the methods have been applied to the determination of enalapril maleate in pharmaceutical dosage forms. Results of analysis are validated statistically.

  2. Optimized and validated spectrophotometric methods for the determination of enalapril maleate in commercial dosage forms.

    Science.gov (United States)

    Rahman, Nafisur; Haque, Sk Manirul

    2008-03-01

    Four simple, rapid and sensitive spectrophotometric methods have been proposed for the determination of enalapril maleate in pharmaceutical formulations. The first method is based on the reaction of carboxylic acid group of enalapril maleate with a mixture of potassium iodate (KIO(3)) and iodide (KI) to form yellow colored product in aqueous medium at 25 +/- 1 degrees C. The reaction is followed spectrophotometrically by measuring the absorbance at 352 nm. The second, third and fourth methods are based on the charge transfer complexation reaction of the drug with p-chloranilic acid (pCA) in 1, 4-dioxan-methanol medium, 2, 3-dichloro 5, 6-dicyano 1, 4-benzoquinone (DDQ) in acetonitrile-1,4 dioxane medium and iodine in acetonitrile-dichloromethane medium. Under optimized experimental conditions, Beer's law is obeyed in the concentration ranges of 2.5-50, 20-560, 5-75 and 10-200 microg mL(-1), respectively. All the methods have been applied to the determination of enalapril maleate in pharmaceutical dosage forms. Results of analysis are validated statistically.

  3. Development and Validation of an HPLC Method for the Analysis of Sirolimus in Drug Products

    Directory of Open Access Journals (Sweden)

    Hadi Valizadeh

    2012-05-01

    Full Text Available Purpose: The aim of this study was to develop a simple, rapid and sensitive reverse phase high performance liquid chromatography (RP-HPLC method for quantification of sirolimus (SRL in pharmaceutical dosage forms. Methods: The chromatographic system employs isocratic elution using a Knauer- C18, 5 mm, 4.6 × 150 mm. Mobile phase consisting of acetonitril and ammonium acetate buffer set at flow rate 1.5 ml/min. The analyte was detected and quantified at 278nm using ultraviolet detector. The method was validated as per ICH guidelines. Results: The standard curve was found to have a linear relationship (r2 > 0.99 over the analytical range of 125–2000ng/ml. For all quality control (QC standards in intraday and interday assay, accuracy and precision range were -0.96 to 6.30 and 0.86 to 13.74 respectively, demonstrating the precision and accuracy over the analytical range. Samples were stable during preparation and analysis procedure. Conclusion: Therefore the rapid and sensitive developed method can be used for the routine analysis of sirolimus such as dissolution and stability assays of pre- and post-marketed dosage forms.

  4. Validated HPLC-Diode Array Detector Method for Simultaneous Evaluation of Six Quality Markers in Coffee.

    Science.gov (United States)

    Gant, Anastasia; Leyva, Vanessa E; Gonzalez, Ana E; Maruenda, Helena

    2015-01-01

    Nicotinic acid, N-methylpyridinium ion, and trigonelline are well studied nutritional biomarkers present in coffee, and they are indicators of thermal decomposition during roasting. However, no method is yet available for their simultaneous determination. This paper describes a rapid and validated HPLC-diode array detector method for the simultaneous quantitation of caffeine, trigonelline, nicotinic acid, N-methylpyridinium ion, 5-caffeoylquinic acid, and 5-hydroxymethyl furfural that is applicable to three coffee matrixes: green, roasted, and instant. Baseline separation among all compounds was achieved in 30 min using a phenyl-hexyl RP column (250×4.6 mm, 5 μm particle size), 0.3% aqueous formic buffer (pH 2.4)-methanol mobile phase at a flow rate of 1 mL/min, and a column temperature at 30°C. The method showed good linear correlation (r2>0.9985), precision (less than 3.9%), sensitivity (LOD=0.023-0.237 μg/mL; LOQ=0.069-0.711 μg/mL), and recovery (84-102%) for all compounds. This simplified method is amenable for a more complete routine evaluation of coffee in industry.

  5. Wall Shear Rate Measurement: Validation of a New Method through Multi-Physics Simulations.

    Science.gov (United States)

    Ricci, Stefano; Swillens, Abigail; Ramalli, Alessandro; Segers, Patrick; Tortoli, Piero

    2016-09-12

    Wall shear stress is known to affect the vessel endothelial function and to be related to important pathologies like the development of atherosclerosis. It is defined as the product of the blood viscosity by the blood velocity gradient at the wall position, i.e. the Wall Shear Rate (WSR). The WSR measurement is particularly challenging in important cardiovascular sites like the carotid bifurcation, because of the related complex flow configurations characterized by high spatial and temporal gradients, wall movement and clutter noise. Moreover, the accuracy of any method for WSR measurement can be effectively tested only if reliable gold standard WSR values, considering all of the aforementioned disturbing effects, are available. Unfortunately, these requirements are difficult to achieve in a physical phantom, so that the accuracy test of novel WSR measurement methods was so far limited to straight pipes and/or similar idealistic configurations. In this work, we propose a new method for WSR measurement and its validation based on a mathematical model of the carotid bifurcation, which, exploiting fluid-structure simulations, is capable of reproducing realistic flow configuration, wall movement, and clutter noise. In particular, the profile near the wall, not directly measurable because affected by clutter, is estimated through a power-law fitting and compared to the gold standard provided by the model. In this condition, the WSR measurements featured an accuracy of ±20%. A preliminary test on a volunteer confirmed the WSR method's feasibility for in-vivo application.

  6. Wall Shear Rate Measurement: Validation of a New Method Through Multiphysics Simulations.

    Science.gov (United States)

    Ricci, Stefano; Swillens, Abigail; Ramalli, Alessandro; Segers, Patrick; Tortoli, Piero

    2017-01-01

    Wall shear stress is known to affect the vessel endothelial function and to be related to important pathologies like the development of atherosclerosis. It is defined as the product of the blood viscosity by the blood velocity gradient at the wall position, i.e., the wall shear rate (WSR). The WSR measurement is particularly challenging in important cardiovascular sites, like the carotid bifurcation, because of the related complex flow configurations characterized by high spatial and temporal gradients, wall movement, and clutter noise. Moreover, accuracy of any method for WSR measurement can be effectively tested only if reliable gold standard WSR values, considering all the aforementioned disturbing effects, are available. Unfortunately, these requirements are difficult to achieve in a physical phantom, so that the accuracy test of the novel WSR measurement methods was so far limited to straight pipes and/or similar idealistic configurations. In this paper, we propose a new method for WSR measurement and its validation based on a mathematical model of the carotid bifurcation, which, exploiting fluid-structure simulations, is capable of reproducing realistic flow configuration, wall movement, and clutter noise. In particular, the profile near the wall, not directly measurable because affected by clutter, is estimated through a power-law fitting and compared with the gold standard provided by the model. In this condition, the WSR measurements featured an accuracy of ±20 %. A preliminary test on a volunteer confirmed the feasibility of the WSR method for in vivo application.

  7. Development and validation of a new method for measuring friction between skin and nonwoven materials.

    Science.gov (United States)

    Cottenden, A M; Wong, W K; Cottenden, D J; Farbrot, A

    2008-07-01

    A new method for measuring the coefficient of friction between nonwoven materials and the curved surface of the volar forearm has been developed and validated. The method was used to measure the coefficient of static friction for three different nonwoven materials on the normal (dry) and over-hydrated volar forearms of five female volunteers (ages 18-44). The method proved simple to run and had good repeatability: the coefficient of variation (standard deviation expressed as a percentage of the mean) for triplets of repeat measurements was usually (80 per cent of the time) less than 10 per cent. Measurements involving the geometrically simpler configuration of pulling a weighted fabric sample horizontally across a quasi-planar area of volar forearm skin proved experimentally more difficult and had poorer repeatability. However, correlations between values of coefficient of static friction derived using the two methods were good (R = 0.81 for normal (dry) skin, and 0.91 for over-hydrated skin). Measurements of the coefficient of static friction for the three nonwovens for normal (dry) and for over-hydrated skin varied in the ranges of about 0.3-0.5 and 0.9-1.3, respectively. In agreement with Amontons' law, coefficients of friction were invariant with normal pressure over the entire experimental range (0.1-8.2 kPa).

  8. The Numerical Welding Simulation - Developments and Validation of Simplified and Bead Lumping Methods

    International Nuclear Information System (INIS)

    Baup, Olivier

    2001-01-01

    The aim of this work was to study the TIG multipass welding process on stainless steel, by means of numerical methods and then to work out simplified and bead lumping methods in order to reduce adjusting and realisation times of these calculations. A simulation was used as reference for the validation of these methods; after the presentation of the test series having led to the option choices of this calculation (2D generalised plane strains, elastoplastic model with an isotropic hardening, hardening restoration due to high temperatures), various simplifications were tried on a plate geometry. These simplifications related various modelling points with a correct plastic flow representation in the plate. The use of a reduced number of thermal fields characterising the bead deposit and a low number of tensile curves allow to obtain interesting results, decreasing significantly the Computing times. In addition various lumping bead methods have been studied and concerning both the shape and the thermic of the macro-deposits. The macro-deposit shapes studied are in 'L', or in layer or they represent two beads one on top of the other. Among these three methods, only those using a few number of lumping beads gave bad results since thermo-mechanical history was deeply modified near and inside the weld. Thereafter, simplified methods have been applied to a tubular geometry. On this new geometry, experimental measurements were made during welding, which allow a validation of the reference calculation. Simplified and reference calculations gave approximately the same stress fields as found on plate geometry. Finally, in the last part of this document a procedure for automatic data setting permitting to reduce significantly the calculation phase preparation is presented. It has been applied to the calculation of thick pipe welding in 90 beads; the results are compared with a simplified simulation realised by Framatome and with experimental measurements. A bead by

  9. Voltammetric determination of copper in selected pharmaceutical preparations--validation of the method.

    Science.gov (United States)

    Lutka, Anna; Maruszewska, Małgorzata

    2011-01-01

    It were established and validated the conditions of voltammetric determination of copper in pharmaceutical preparations. The three selected preparations: Zincuprim (A), Wapń, cynk, miedź z wit. C (B), Vigor complete (V) contained different salts and different quantity of copper (II) and increasing number of accompanied ingredients. For the purpose to transfer copper into solution, the samples of powdered tablets of the first and second preparation were undergone extraction and of the third the mineralization procedures. The concentration of copper in solution was determined by differential pulse voltammetry (DP) using comparison with standard technique. In the validation process, the selectivity, accuracy, precision and linearity of DP determination of copper in three preparations were estimated. Copper was determined within the concentration range of 1-9 ppm (1-9 microg/mL): the mean recoveries approached 102% (A), 100% (B), 102% (V); the relative standard deviations of determinations (RSD) were 0.79-1.59% (A), 0.62-0.85% (B) and 1.68-2.28% (V), respectively. The mean recoveries and the RSDs of determination satisfied the requirements for the analyte concentration at the level 1-10 ppm. The statistical verification confirmed that the tested voltammetric method is suitable for determination of copper in pharmaceutical preparation.

  10. Verification and Validation of a Coordinate Transformation Method in Axisymmetric Transient Magnetics.

    Energy Technology Data Exchange (ETDEWEB)

    Ashcraft, C. Chace [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Niederhaus, John Henry [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Robinson, Allen C. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

    2016-01-29

    We present a verification and validation analysis of a coordinate-transformation-based numerical solution method for the two-dimensional axisymmetric magnetic diffusion equation, implemented in the finite-element simulation code ALEGRA. The transformation, suggested by Melissen and Simkin, yields an equation set perfectly suited for linear finite elements and for problems with large jumps in material conductivity near the axis. The verification analysis examines transient magnetic diffusion in a rod or wire in a very low conductivity background by first deriving an approximate analytic solution using perturbation theory. This approach for generating a reference solution is shown to be not fully satisfactory. A specialized approach for manufacturing an exact solution is then used to demonstrate second-order convergence under spatial refinement and tem- poral refinement. For this new implementation, a significant improvement relative to previously available formulations is observed. Benefits in accuracy for computed current density and Joule heating are also demonstrated. The validation analysis examines the circuit-driven explosion of a copper wire using resistive magnetohydrodynamics modeling, in comparison to experimental tests. The new implementation matches the accuracy of the existing formulation, with both formulations capturing the experimental burst time and action to within approximately 2%.

  11. Verification and Validation of a Chemical Reaction Solver Coupled to the Piecewise Parabolic Method

    Science.gov (United States)

    Attal, Nitesh; Ramaprabhu, Praveen; Hossain, Jahed; Karkhanis, Varad; Roy, Sukesh; Gord, James; Uddin, Mesbah

    2012-11-01

    We present a detailed chemical kinetics reaction solver coupled to the Piecewise Parabolic Method (PPM) embedded in the widely used astrophysical FLASH code. The FLASH code solves the compressible Euler equations with a directionally split, PPM with Adaptive Mesh Refinement (AMR). The reaction network is solved using a library of coupled ODE solvers, specialized for handling stiff systems of equations. Finally, the diffusion of heat, mass, and momentum is handled either through an update of the fluxes of each quantity, or by directly solving a diffusion equation for each. The resulting product is capable of handling a variety of physics such as gas-phase chemical kinetics, diffusive transport of mass, momentum, and heat, shocks, sharp interfaces, multi-species mixtures, and thermal radiation. We will present results from verification and validation of the above capabilities through comparison with analytical solutions, and published numerical and experimental data. Our validation cases include advection of reacting fronts in 1-D and 2D, laminar premixed flames in a Bunsen burner configuration, and shock-driven combustion. We acknowledge funding from Spectral Energies LLC.

  12. Optimization and Validation of an ETAAS Method for the Determination of Nickel in Postmortem Material.

    Science.gov (United States)

    Dudek-Adamska, Danuta; Lech, Teresa; Kościelniak, Paweł

    2015-01-01

    In this article, optimization and validation of a procedure for the determination of total nickel in wet digested samples of human body tissues (internal organs) for forensic toxicological purposes are presented. Four experimental setups of the electrothermal atomic absorption spectrometry (ETAAS) using a Solaar MQZe (Thermo Electron Co.) were compared, using the following (i) no modifier, (ii) magnesium nitrate, (iii) palladium nitrate and (iv) magnesium nitrate and ammonium dihydrogen phosphate mixture as chemical modifiers. It was ascertained that the ETAAS without any modifier with 1,300/2,400°C as the pyrolysis and atomization temperatures, respectively, can be used to determine total nickel at reference levels in biological materials as well as its levels found in chronic or acute poisonings. The method developed was validated, obtaining a linear range of calibration from 0.76 to 15.0 μg/L, limit of detection at 0.23 µg/L, limit of quantification at 0.76 µg/L, precision (as relative standard deviation) up to 10% and accuracy of 97.1% for the analysis of certified material (SRM 1577c Bovine Liver) and within a range from 99.2 to 109.9% for the recovery of fortified liver samples. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  13. Multiple bioanalytical method to reveal developmental biological responses in zebrafish embryos exposed to triclocarban.

    Science.gov (United States)

    Dong, Xing; Xu, Hai; Wu, Xiangyang; Yang, Liuqing

    2018-02-01

    Triclocarban (TCC) is a well-known antibacterial agent that is frequently detected in environmental, wildlife and human samples. The potential toxicological effects and action mechanism of TCC on vertebrate development has remained unclear. In the present study, we analyzed phenotypic alterations, thyroid hormone levels, thyroid hormone responsive genes, and proteomic profiles of zebrafish embryos after exposure to a series of concentrations of TCC from 6 h post-fertilization (hpf) to 120 hpf. The most nonlethal concentration (MNLC), lethal concentration 10% (LC 10 ) and lethal concentration 50% (LC 50 ) of TCC for exposures of 96 h were 133.3 μg/L, 147.5 μg/L and 215.8 μg/L, respectively. Our results showed that exposure to TCC decreased heart rate, delayed yolk absorption and swim bladder development at MNLC and LC 10 . Exposure to MNLC of TCC inhibited thyroid hormone and altered expression of thyroid hormone responsive genes. Furthermore, exposure to 1/20 MNLC of TCC altered expression of proteins related to binding and metabolism, skeletal muscle development and function, as well as proteins involved in nervous system development and immune response, indicating TCC has potential health risks in wildlife and humans at low concentration level. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. A bioanalytical method to determine the cell wall composition of Mycobacterium tuberculosis grown in vivo.

    Science.gov (United States)

    Bhamidi, Suresh; Shi, Libin; Chatterjee, Delphi; Belisle, John T; Crick, Dean C; McNeil, Michael R

    2012-02-01

    Mycobacterium tuberculosis bacilli exhibit cell wall alterations during in vivo growth. Development of ultrasensitive analytical techniques with high specificities is required to analyze the cell wall of M. tuberculosis isolated from experimental animals because of the low amounts of bacteria available and contamination by host tissue. Here we present a novel methodology to analyze all three major components (mycolic acids, arabinogalactan, and peptidoglycan) of the mycobacterial cell wall from mycobacteria isolated from animal tissue. In this procedure, the cell wall carbohydrates are analyzed by gas chromatography tandem mass spectrometry (GC/MS/MS) of alditol acetates, the peptidoglycan by GC/MS (mass spectrometry) analysis of the unique amino acid diaminopimelic acid (after derivatization with isopropyl chloroformate), and the mycolic acids by liquid chromatography (LC)/MS (negative ion) without derivatization. The procedure was designed so that all three analyses could be performed starting with a single sample given the difficulty of preparing multiple aliquots in known ratios. Linkage analysis, including an enantiomeric specific procedure, of the arabinogalactan polymer is also presented. These procedures will enable the determination of the cell wall alterations known to occur in the important nongrowing "dormant" M. tuberculosis present during disease. With some adaptations, the methodology is also applicable to the analysis of small amounts of in vivo grown bacteria of other species. Copyright © 2011 Elsevier Inc. All rights reserved.

  15. The use of Geographic Information System (GIS) and non-GIS methods to assess the external validity of samples postcollection.

    Science.gov (United States)

    Richardson, Esther; Good, Margaret; McGrath, Guy; More, Simon J

    2009-09-01

    External validity is fundamental to veterinary diagnostic investigation, reflecting the accuracy with which sample results can be extrapolated to a broader population of interest. Probability sampling methods are routinely used during the collection of samples from populations, specifically to maximize external validity. Nonprobability sampling (e.g., of blood samples collected as part of routine surveillance programs or laboratory submissions) may provide useful data for further posthoc epidemiological analysis, adding value to the collection and submission of samples. As the sample has already been submitted, the analyst or investigator does not have any control over the sampling methodology, and hence external validity as routine probability sampling methods may not have been employed. The current study describes several Geographic Information System (GIS) and non-GIS methods, applied posthoc, to assess the external validity of samples collected using both probability and nonprobability sampling methods. These methods could equally be employed for inspecting other datasets. Mapping was conducted using ArcView 9.1. Based on this posthoc assessment, results from the random field sample could provide an externally valid, albeit relatively imprecise, estimate of national disease prevalence, of disease prevalence in 3 of the 4 provinces (all but Ulster, in the north and northwest, where sample size was small), and in beef and dairy herds. This study provides practical methods for examining the external validity of samples postcollection.

  16. Experimental validation of a method for removing the capacitive leakage artifact from electrical bioimpedance spectroscopy measurements

    International Nuclear Information System (INIS)

    Buendia, R; Seoane, F; Gil-Pita, R

    2010-01-01

    Often when performing electrical bioimpedance (EBI) spectroscopy measurements, the obtained EBI data present a hook-like deviation, which is most noticeable at high frequencies in the impedance plane. The deviation is due to a capacitive leakage effect caused by the presence of stray capacitances. In addition to the data deviation being remarkably noticeable at high frequencies in the phase and the reactance spectra, the measured EBI is also altered in the resistance and the modulus. If this EBI data deviation is not properly removed, it interferes with subsequent data analysis processes, especially with Cole model-based analyses. In other words, to perform any accurate analysis of the EBI spectroscopy data, the hook deviation must be properly removed. Td compensation is a method used to compensate the hook deviation present in EBI data; it consists of multiplying the obtained spectrum, Z meas (ω), by a complex exponential in the form of exp(–jωTd). Although the method is well known and accepted, Td compensation cannot entirely correct the hook-like deviation; moreover, it lacks solid scientific grounds. In this work, the Td compensation method is revisited, and it is shown that it should not be used to correct the effect of a capacitive leakage; furthermore, a more developed approach for correcting the hook deviation caused by the capacitive leakage is proposed. The method includes a novel correcting expression and a process for selecting the proper values of expressions that are complex and frequency dependent. The correctness of the novel method is validated with the experimental data obtained from measurements from three different EBI applications. The obtained results confirm the sufficiency and feasibility of the correcting method

  17. An assessment to evaluate the validity of different methods for the description of some corrosion inhibitors.

    Science.gov (United States)

    Aboelnga, M M; Awad, M K; Gauld, J W; Mustafa, M R

    2014-09-01

    New research and development efforts using computational chemistry in studying an assessment of the validity of different quantum chemical methods to describe the molecular and electronic structures of some corrosion inhibitors were introduced. The standard and the highly accurate CCSD method with 6-311++G(d,p), ab initio calculations using the HF/6-31G++(d,p) and MP2 with 6-311G(d,p), 6-31++G(d,p), and 6-311++G(2df,p) methods as well as DFT method at the B3LYP, BP86, B3LYP*, M06L, and M062x/6-31G++(d,p) basis set level were performed on some triazole derivatives and sulfur containing compounds used as corrosion inhibitors. Quantum chemical parameters, such as the energy of the highest occupied molecular orbital energy (E(HOMO)), the energy of the lowest unoccupied molecular orbital energy (E(LUMO)), energy gap (ΔE), dipole moment (μ), sum of total negative charges (TNC), chemical potential (Pi), electronegativity (χ), hardness (η), softness (σ), local softness (s), Fukui functions (f (+),f (-)), electrophilicity (ω), the total energy change (∆E(T)) and the solvation energy (S.E), were calculated. Furthermore, the accuracy and the applicability of these methods were estimated relative to the highest accuracy and standard CCSD with 6-311++G(d,p) method. Good correlations between the quantum chemical parameters and the corresponding inhibition efficiency (IE%) were found.

  18. Validation of an HPLC method for quantification of total quercetin in Calendula officinalis extracts

    International Nuclear Information System (INIS)

    Muñoz Muñoz, John Alexander; Morgan Machado, Jorge Enrique; Trujillo González, Mary

    2015-01-01

    Introduction: calendula officinalis extracts are used as natural raw material in a wide range of pharmaceutical and cosmetic preparations; however, there are no official methods for quality control of these extracts. Objective: to validate an HPLC-based analytical method for quantification total quercetin in glycolic and hydroalcoholic extracts of Calendula officinalis. Methods: to quantify total quercetin content in the matrices, it was necessary to hydrolyze flavonoid glycosides under optimal conditions. The chromatographic separation was performed on a C-18 SiliaChrom 4.6x150 mm 5 µm column, adapted to a SiliaChrom 5 um C-18 4.6x10 mm precolumn, with UV detection at 370 nm. The gradient elution was performed with a mobile phase consisting of methanol (MeOH) and phosphoric acid (H 3 PO 4 ) (0.08 % w/v). The quantification was performed through the external standard method and comparison with quercetin reference standard. Results: the studied method selectivity against extract components and degradation products under acid/basic hydrolysis, oxidation and light exposure conditions showed no signals that interfere with the quercetin quantification. It was statistically proved that the method is linear from 1.0 to 5.0 mg/mL. Intermediate precision expressed as a variation coefficient was 1.8 and 1.74 % and the recovery percentage was 102.15 and 101.32 %, for glycolic and hydroalcoholic extracts, respectively. Conclusions: the suggested methodology meets the quality parameters required for quantifying total quercetin, which makes it a useful tool for quality control of C. officinalis extracts. (author)

  19. Validation of the Gatortail method for accurate sizing of pulmonary vessels from 3D medical images.

    Science.gov (United States)

    O'Dell, Walter G; Gormaley, Anne K; Prida, David A

    2017-12-01

    Detailed characterization of changes in vessel size is crucial for the diagnosis and management of a variety of vascular diseases. Because clinical measurement of vessel size is typically dependent on the radiologist's subjective interpretation of the vessel borders, it is often prone to high inter- and intra-user variability. Automatic methods of vessel sizing have been developed for two-dimensional images but a fully three-dimensional (3D) method suitable for vessel sizing from volumetric X-ray computed tomography (CT) or magnetic resonance imaging has heretofore not been demonstrated and validated robustly. In this paper, we refined and objectively validated Gatortail, a method that creates a mathematical geometric 3D model of each branch in a vascular tree, simulates the appearance of the virtual vascular tree in a 3D CT image, and uses the similarity of the simulated image to a patient's CT scan to drive the optimization of the model parameters, including vessel size, to match that of the patient. The method was validated with a 2-dimensional virtual tree structure under deformation, and with a realistic 3D-printed vascular phantom in which the diameter of 64 branches were manually measured 3 times each. The phantom was then scanned on a conventional clinical CT imaging system and the images processed with the in-house software to automatically segment and mathematically model the vascular tree, label each branch, and perform the Gatortail optimization of branch size and trajectory. Previously proposed methods of vessel sizing using matched Gaussian filters and tubularity metrics were also tested. The Gatortail method was then demonstrated on the pulmonary arterial tree segmented from a human volunteer's CT scan. The standard deviation of the difference between the manually measured and Gatortail-based radii in the 3D physical phantom was 0.074 mm (0.087 in-plane pixel units for image voxels of dimension 0.85 × 0.85 × 1.0 mm) over the 64 branches

  20. Pharmacokinetics and brain uptake study of novel AMPA receptor antagonist perampanel in SD rats using a validated UHPLC-QTOF-MS method.

    Science.gov (United States)

    Paul, David; Allakonda, Lingesh; Sahu, Amit; Surendran, Shruti; Satheeshkumar, Nanjappan

    2018-02-05

    Perampanel (PER) is a novel AMPA receptor antagonist for antiepileptic therapy and is prospective for the treatment of other neurological disorders. A highly sensitive and rapid UHPLC-QTOF-MS method was developed for the quantification of PER in plasma/brain homogenate of SD rat with alogliptin as an internal standard (IS). Chromatographic separation was carried out on an Acquity UPLC HSS Cyano column (100mm×2.1mm, 1.8μm) using gradient mobile phase consisting of 0.1% formic acid and acetonitrile at a flow rate of 0. 4mL/min. Sample preparation was carried out by a simple protein precipitation method. The mass spectrometric analysis of target ions at [M+H] + m/z 350.1288 for PER and m/z 340.1779 for IS was monitored with extracted ion chromatography. The developed analytical method meets the US-FDA and EMA bioanalytical guidelines and was found to be precise, accurate, selective and rugged. It exhibited good sensitivity (0.4ng/mL) and linearity over a range of 0.4-400ng/mL in both the bio-matrices. The method was successfully applied to pharmacokinetics and brain uptake study of PER after oral administration to SD rats. The study results showed PER has penetrated the blood-brain barrier, brain to plasma ratio (Kp) was found to be 0.62±0.05 and its rapidly eliminated from the brain. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. A validated HPTLC method for determination of terbutaline sulfate in biological samples: Application to pharmacokinetic study

    OpenAIRE

    Faiyazuddin, Md.; Rauf, Abdul; Ahmad, Niyaz; Ahmad, Sayeed; Iqbal, Zeenat; Talegaonkar, Sushma; Bhatnagar, Aseem; Khar, Roop K.; Ahmad, Farhan J.

    2011-01-01

    Terbutaline sulfate (TBS) was assayed in biological samples by validated HPTLC method. Densitometric analysis of TBS was carried out at 366 nm on precoated TLC aluminum plates with silica gel 60F254 as a stationary phase and chloroform–methanol (9.0:1.0, v/v) as a mobile phase. TBS was well resolved at RF 0.34 ± 0.02. In all matrices, the calibration curve appeared linear (r2 ⩾ 0.9943) in the tested range of 100–1000 ng spot−1 with a limit of quantification of 18.35 ng spot−1. Drug recovery f...

  2. A Method of Retrospective Computerized System Validation for Drug Manufacturing Software Considering Modifications

    Science.gov (United States)

    Takahashi, Masakazu; Fukue, Yoshinori

    This paper proposes a Retrospective Computerized System Validation (RCSV) method for Drug Manufacturing Software (DMSW) that relates to drug production considering software modification. Because DMSW that is used for quality management and facility control affects big impact to quality of drugs, regulatory agency required proofs of adequacy for DMSW's functions and performance based on developed documents and test results. Especially, the work that explains adequacy for previously developed DMSW based on existing documents and operational records is called RCSV. When modifying RCSV conducted DMSW, it was difficult to secure consistency between developed documents and test results for modified DMSW parts and existing documents and operational records for non-modified DMSW parts. This made conducting RCSV difficult. In this paper, we proposed (a) definition of documents architecture, (b) definition of descriptive items and levels in the documents, (c) management of design information using database, (d) exhaustive testing, and (e) integrated RCSV procedure. As a result, we could conduct adequate RCSV securing consistency.

  3. Validation of qPCR Methods for the Detection of Mycobacterium in New World Animal Reservoirs

    Science.gov (United States)

    Housman, Genevieve; Malukiewicz, Joanna; Boere, Vanner; Grativol, Adriana D.; Pereira, Luiz Cezar M.; Silva, Ita de Oliveira e; Ruiz-Miranda, Carlos R.; Truman, Richard; Stone, Anne C.

    2015-01-01

    Zoonotic pathogens that cause leprosy (Mycobacterium leprae) and tuberculosis (Mycobacterium tuberculosis complex, MTBC) continue to impact modern human populations. Therefore, methods able to survey mycobacterial infection in potential animal hosts are necessary for proper evaluation of human exposure threats. Here we tested for mycobacterial-specific single- and multi-copy loci using qPCR. In a trial study in which armadillos were artificially infected with M. leprae, these techniques were specific and sensitive to pathogen detection, while more traditional ELISAs were only specific. These assays were then employed in a case study to detect M. leprae as well as MTBC in wild marmosets. All marmosets were negative for M. leprae DNA, but 14 were positive for the mycobacterial rpoB gene assay. Targeted capture and sequencing of rpoB and other MTBC genes validated the presence of mycobacterial DNA in these samples and revealed that qPCR is useful for identifying mycobacterial-infected animal hosts. PMID:26571269

  4. Validation of qPCR Methods for the Detection of Mycobacterium in New World Animal Reservoirs.

    Science.gov (United States)

    Housman, Genevieve; Malukiewicz, Joanna; Boere, Vanner; Grativol, Adriana D; Pereira, Luiz Cezar M; Silva, Ita de Oliveira; Ruiz-Miranda, Carlos R; Truman, Richard; Stone, Anne C

    2015-11-01

    Zoonotic pathogens that cause leprosy (Mycobacterium leprae) and tuberculosis (Mycobacterium tuberculosis complex, MTBC) continue to impact modern human populations. Therefore, methods able to survey mycobacterial infection in potential animal hosts are necessary for proper evaluation of human exposure threats. Here we tested for mycobacterial-specific single- and multi-copy loci using qPCR. In a trial study in which armadillos were artificially infected with M. leprae, these techniques were specific and sensitive to pathogen detection, while more traditional ELISAs were only specific. These assays were then employed in a case study to detect M. leprae as well as MTBC in wild marmosets. All marmosets were negative for M. leprae DNA, but 14 were positive for the mycobacterial rpoB gene assay. Targeted capture and sequencing of rpoB and other MTBC genes validated the presence of mycobacterial DNA in these samples and revealed that qPCR is useful for identifying mycobacterial-infected animal hosts.

  5. Results of a survey on accident and safety analysis codes, benchmarks, verification and validation methods

    International Nuclear Information System (INIS)

    Lee, A.G.; Wilkin, G.B.

    1996-03-01

    During the 'Workshop on R and D needs' at the 3rd Meeting of the International Group on Research Reactors (IGORR-III), the participants agreed that it would be useful to compile a survey of the computer codes and nuclear data libraries used in accident and safety analyses for research reactors and the methods various organizations use to verify and validate their codes and libraries. Five organizations, Atomic Energy of Canada Limited (AECL, Canada), China Institute of Atomic Energy (CIAE, People's Republic of China), Japan Atomic Energy Research Institute (JAERI, Japan), Oak Ridge National Laboratories (ORNL, USA), and Siemens (Germany) responded to the survey. The results of the survey are compiled in this report. (author) 36 refs., 3 tabs

  6. Dynamic fracture tests for flawed nuclear piping and validation of LBB evaluation method

    International Nuclear Information System (INIS)

    Kashima, K.

    1998-01-01

    The international research program, 'IPIRG program', was proposed and managed by U.S. Nuclear Regulatory Commission from 1987 to 1996 to develop a fracture database and validate fracture mechanics technology for assessing the integrity of flawed nuclear piping. Seventeen Japanese organizations, including utilities companies, vendors and CRIEPI (the representative) jointly participated in the program. Many full-scale fracture tests, using US and Japanese pipes, were conducted under dynamic and cyclic loadings, simulating seismic conditions. The results from tests on Japanese pipes showed that the current LBB (Leak-Before-Break) evaluation method for Japanese pipes, originally developed and demonstrated for relatively small-diameter pipes subjected to quasi-static loading, could also be applied to large-diameter pipes and dynamic loading. (author)

  7. A systematic review of validated methods for identifying Bell's palsy using administrative or claims data.

    Science.gov (United States)

    Lee, Christopher D; Carnahan, Ryan M; McPheeters, Melissa L

    2013-12-30

    To identify and assess billing, procedural, or diagnosis code, or pharmacy claims-based algorithms used to identify Bell's palsy in administrative and claims databases. We searched the MEDLINE database via PubMed from 1991 to September 2012 using controlled vocabulary and key terms related to Bell's palsy. We also searched the reference lists of included studies. Two investigators independently assessed the full text of studies against pre-determined inclusion criteria. Two reviewers independently extracted data regarding participant and algorithm characteristics and assessed a study's methodologic rigor. One study identified Bell's palsy using an algorithm that included ICD-9 code 351.x and H-ICDA code 350.x, and two other studies analyzed a dataset for ICD-9 code 351.0. The positive predictive values of these studies were 0.81 and 0.88, based on case adjudication of ICD-9 matches. Two further studies calculated incidence rates without validation of their methods, also including ICD-9 code 351.0. No study reported the sensitivity of algorithms to identify Bell's palsy. Few publications used rigorous methods to identify a validated algorithm that could identify cases of Bell's palsy from an administrative database. The best evidence from two different datasets in the literature addressed in this review used ICD-9 code 351.0 or a collection of ICD-9 codes 351.x for facial nerve disorders including Bell's palsy, along with other ICD-9 and H-ICDA codes for facial weakness. Each study had acceptable PPV, suggesting that ICD-9 based-algorithms have some utility in detecting Bell's palsy cases. Copyright © 2013 Elsevier Ltd. All rights reserved.

  8. DEVELOPMENT AND VALIDATION OF 2P2S INSTRUMENT BY MIX METHODS

    Directory of Open Access Journals (Sweden)

    Nancy Ng Yut Kuan

    2017-12-01

    Full Text Available Lack of pedagogical content knowledge in questioning skills and how they were observed, lack of co-operation and not diversified teaching methods that can stimulate the cognitive, psychomotor and affective domains in students, making all of these gaps in the research literature. Thus, the researchers makes the development and validation of instruments for identifying Mathematics teachers perception about knowledge, simulation models, clinical observation and synergy (2P2S in Professional Learning Community: Lesson Study. The population is consist of primary and secondary schools in three districts as known Beluran, Telupid and Sandakan, in the such eastern part of Sabah. The samples were the 30 primary Mathematics teachers who were non randomly and purposive selected who have been teaching at least more than 1 year. In mix methods, researchers can analyzed and used the model IDCV which contains 10 detailed and interactive phases to develop quantitative instrument optimally. The revised 2P2S instrument validation phase of quantitative analysis involves Rasch measurement model. This instrument has good person reliability at 0.90 and an excellent item realibility at 0.92. This instrument has a Standard Error of Measurement (SE which is low, ± 0.19 logit. Both Infit MNSQ and the z-std are close to ideal value of 1 and 0 [(Infit MNSQ Person = 0.97; z-std = -0.1, (Infit MNSQ Item = 0.98; z-std = 0.0] which is you can imagine the suitability of instruments to measure what should be measured based on the underlying theorems.

  9. Rapid validated HPTLC method for estimation of betulinic acid in Nelumbo nucifera (Nymphaeaceae) rhizome extract.

    Science.gov (United States)

    Mukherjee, Debajyoti; Kumar, N Satheesh; Khatua, Taraknath; Mukherjee, Pulok K

    2010-01-01

    Betulinic acid (pentacyclic triterpenoid) is an important marker component present in Nelumbo nucifera Gaertn. rhizome. N. nucifera rhizome has several medicinal uses including hypoglycaemic, antidiarrhoeal, antimicrobial, diuretic, antipyretic, psychopharmacological activities. To establish a simple, sensitive, reliable, rapid and validated high-performance thin-layer chromatography method for estimation of betulinic acid in hydro-alcoholic extract of N. nucifera Gaertn. rhizome. The separation was carried out on a thin-layer chromatography aluminium plate pre-coated with silica gel 60F(254) , eluted with chloroform, methanol and formic acid (49 : 1 : 1 v/v). Post chromatographic derivatisation was done with anisaldehyde-sulphuric acid reagent and densitometric scanning was performed using a Camag TLC scanner III, at 420 nm. The system was found to produce a compact spot for betulinic acid (R(f) = 0.30). A good linear precision relationship between the concentrations (2-10 µg) and peak areas were obtained with the correlation coefficient (r) of 0.99698. The limit of detection and limit of quantification of betulinic acid were detected to be 0.4 and 2.30 µg per spot. The percentage of recovery was found to be 98.36%. The percentage relative standard deviations of intra-day and inter-day precisions were 0.82-0.394 and 0.85-0.341, respectively. This validated HPTLC method provides a new and powerful approach to estimate betulinic acid as phytomarker in the extract. Copyright © 2010 John Wiley & Sons, Ltd.

  10. Validation of a spectrophotometric method to determine ciprofibrate content in tablets

    Directory of Open Access Journals (Sweden)

    Guilherme Nobre Lima do Nascimento

    2011-03-01

    Full Text Available Ciprofibrate is a drug indicated in cases of hypertriglyceridemia and mixed hyperlipidemia, but no monographs are available in official compendia for the analysis of this substance in tablets. The objective of this work was to develop and validate a spectrophotometric method for routine analysis of ciprofibrate in tablets. In this study, commercial and standard ciprofibrate were used, as well as placebo in absolute ethanol, analyzed by UV spectrophotometer. All tests followed the rules of Resolution RE-899, 2003. The results showed that the developed and validated method offers low cost, easy implementation, precision and accuracy, and may be included in the routine of quality control laboratories.O ciprofibrato é um fármaco indicado em casos de hipertrigliceridemia e hiperlipidemia mista, mas não há monografias em compêndios oficiais para a análise desta substância em comprimidos. O objetivo deste trabalho é desenvolver e validar um método espectrofotométrico para análise de rotina de ciprofibrato em comprimidos. Neste estudo foram empregados ciprofibrato comercial, padrão e placebo em etanol absoluto, analisadas por espectrofotometria UV. Todos os testes seguiram as regras da Resolução RE- 899, 2003. Os resultados mostraram que o método desenvolvido e validado apresenta baixo custo, fácil implementação, precisão e exatidão e pode ser incluído em rotina de laboratórios de controle de qualidade.

  11. VALIDATION OF ANALYTICAL METHODS AND INSTRUMENTATION FOR BERYLLIUM MEASUREMENT: REVIEW AND SUMMARY OF AVAILABLE GUIDES, PROCEDURES, AND PROTOCOLS

    Energy Technology Data Exchange (ETDEWEB)

    Ekechukwu, A

    2009-05-27

    Method validation is the process of evaluating whether an analytical method is acceptable for its intended purpose. For pharmaceutical methods, guidelines from the United States Pharmacopeia (USP), International Conference on Harmonisation (ICH), and the United States Food and Drug Administration (USFDA) provide a framework for performing such valications. In general, methods for regulatory compliance must include studies on specificity, linearity, accuracy, precision, range, detection limit, quantitation limit, and robustness. Elements of these guidelines are readily adapted to the issue of validation for beryllium sampling and analysis. This document provides a listing of available sources which can be used to validate analytical methods and/or instrumentation for beryllium determination. A literature review was conducted of available standard methods and publications used for method validation and/or quality control. A comprehensive listing of the articles, papers and books reviewed is given in the Appendix. Available validation documents and guides are listed therein; each has a brief description of application and use. In the referenced sources, there are varying approches to validation and varying descriptions of the valication process at different stages in method development. This discussion focuses on valication and verification of fully developed methods and instrumentation that have been offered up for use or approval by other laboratories or official consensus bodies such as ASTM International, the International Standards Organization (ISO) and the Association of Official Analytical Chemists (AOAC). This review was conducted as part of a collaborative effort to investigate and improve the state of validation for measuring beryllium in the workplace and the environment. Documents and publications from the United States and Europe are included. Unless otherwise specified, all referenced documents were published in English.

  12. Suspended sediment assessment by combining sound attenuation and backscatter measurements - analytical method and experimental validation

    Science.gov (United States)

    Guerrero, Massimo; Di Federico, Vittorio

    2018-03-01

    The use of acoustic techniques has become common for estimating suspended sediment in water environments. An emitted beam propagates into water producing backscatter and attenuation, which depend on scattering particles concentration and size distribution. Unfortunately, the actual particles size distribution (PSD) may largely affect the accuracy of concentration quantification through the unknown coefficients of backscattering strength, ks2, and normalized attenuation, ζs. This issue was partially solved by applying the multi-frequency approach. Despite this possibility, a relevant scientific and practical question remains regarding the possibility of using acoustic methods to investigate poorly sorted sediment in the spectrum ranging from clay to fine sand. The aim of this study is to investigate the possibility of combining the measurement of sound attenuation and backscatter to determine ζs for the suspended particles and the corresponding concentration. The proposed method is moderately dependent from actual PSD, thus relaxing the need of frequent calibrations to account for changes in ks2 and ζs coefficients. Laboratory tests were conducted under controlled conditions to validate this measurement technique. With respect to existing approaches, the developed method more accurately estimates the concentration of suspended particles ranging from clay to fine sand and, at the same time, gives an indication on their actual PSD.

  13. Validation of the abbreviated Radon Progeny Integrating Sampling Unit (RPISU) method for Mesa County, Colorado

    International Nuclear Information System (INIS)

    Langner, G.H. Jr.

    1987-06-01

    The US Department of Energy (DOE) Office of Remedial Action and Waste Technology established the Technical Measurements Center at the DOE Grand Junction, Colorado, Projects Office to standardize, calibrate, and compare measurements made in support of DOE remedial action programs. Indoor radon-daughter concentration measurements are made to determine whether a structure is in need of remedial action. The Technical Measurements Center conducted this study to validate an abbreviated Radon Progeny Integrated Sampling Unit (RPISU) method of making indoor radon-daughter measurements to determine whether a structure has a radon-daughter concentration (RDC) below the levels specified in various program standards. The Technical Measurements Center established a criterion against which RDC measurements made using the RPISU sampling method are evaluated to determine if sampling can be terminated or whether further measurements are required. This abbreviated RPISU criterion was tested against 317 actual sets of RPISU data from measurements made over an eight-year period in Mesa County, Colorado. The data from each location were tested against a standard that was assumed to be the same as the actual annual average RDC from that location. At only two locations was the criterion found to fail. Using the abbreviated RPISU method, only 0.6% of locations sampled can be expected to be falsely indicated as having annual average RDC levels below a given standard

  14. An overview of experimental designs in HPLC method development and validation.

    Science.gov (United States)

    Sahu, Prafulla Kumar; Ramisetti, Nageswara Rao; Cecchi, Teresa; Swain, Suryakanta; Patro, Chandra Sekhar; Panda, Jagadeesh

    2018-01-05

    Chemometric approaches have been increasingly viewed as precious complements to high performance liquid chromatographic practices, since a large number of variables can be simultaneously controlled to achieve the desired separations. Moreover, their applications may efficiently identify and optimize the significant factors to accomplish competent results through limited experimental trials. The present manuscript discusses usefulness of various chemometric approaches in high and ultra performance liquid chromatography for (i) methods development from dissolution studies and sample preparation to detection, considering the progressive substitution of traditional detectors with tandem mass spectrometry instruments and the importance of stability indicating assays (ii) method validation through screening and optimization designs. Choice of appropriate types of experimental designs so as to either screen the most influential factors or optimize the selected factors' combination and the mathematical models in chemometry have been briefly recalled and the advantages of chemometric approaches have been emphasized. The evolution of the design of experiments to the Quality by Design paradigm for method development has been reviewed and the Six Sigma practice as a quality indicator in chromatography has been explained. Chemometric applications and various strategies in chromatographic separations have been described. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Development and validation of a new fallout transport method using variable spectral winds

    International Nuclear Information System (INIS)

    Hopkins, A.T.

    1984-01-01

    A new method was developed to incorporate variable winds into fallout transport calculations. The method uses spectral coefficients derived by the National Meteorological Center. Wind vector components are computed with the coefficients along the trajectories of falling particles. Spectral winds are used in the two-step method to compute dose rate on the ground, downwind of a nuclear cloud. First, the hotline is located by computing trajectories of particles from an initial, stabilized cloud, through spectral winds to the ground. The connection of particle landing points is the hotline. Second, dose rate on and around the hotline is computed by analytically smearing the falling cloud's activity along the ground. The feasibility of using spectral winds for fallout particle transport was validated by computing Mount St. Helens ashfall locations and comparing calculations to fallout data. In addition, an ashfall equation was derived for computing volcanic ash mass/area on the ground. Ashfall data and the ashfall equation were used to back-calculate an aggregated particle size distribution for the Mount St. Helens eruption cloud

  16. Comparison and validation of statistical methods for predicting power outage durations in the event of hurricanes.

    Science.gov (United States)

    Nateghi, Roshanak; Guikema, Seth D; Quiring, Steven M

    2011-12-01

    This article compares statistical methods for modeling power outage durations during hurricanes and examines the predictive accuracy of these methods. Being able to make accurate predictions of power outage durations is valuable because the information can be used by utility companies to plan their restoration efforts more efficiently. This information can also help inform customers and public agencies of the expected outage times, enabling better collective response planning, and coordination of restoration efforts for other critical infrastructures that depend on electricity. In the long run, outage duration estimates for future storm scenarios may help utilities and public agencies better allocate risk management resources to balance the disruption from hurricanes with the cost of hardening power systems. We compare the out-of-sample predictive accuracy of five distinct statistical models for estimating power outage duration times caused by Hurricane Ivan in 2004. The methods compared include both regression models (accelerated failure time (AFT) and Cox proportional hazard models (Cox PH)) and data mining techniques (regression trees, Bayesian additive regression trees (BART), and multivariate additive regression splines). We then validate our models against two other hurricanes. Our results indicate that BART yields the best prediction accuracy and that it is possible to predict outage durations with reasonable accuracy. © 2011 Society for Risk Analysis.

  17. Validation of the cleaning and sanitization method for radiopharmaceutical production facilities

    International Nuclear Information System (INIS)

    Robles, Anita; Morote, Mario; Moore, Mariel; Castro, Delcy; Paragulla, Wilson; Novoa, Carlos; Otero, Manuel; Miranda, Jesus; Herrera, Jorge; Gonzales, Luis

    2014-01-01

    A protocol for the cleaning and sanitization method for radiopharmaceutical production facilities has been designed and developed for the inner surface of the hot cells for the production of Sodium Pertechnetate Tc-99m and Sm-153 EDTMP, considering an extreme situation for each hot cell. Cleaning is performed with double-distilled water and sanitation with two disinfectant solutions, 70 % isopropyl alcohol and 3 % hydrogen peroxide in alternate weeks. Microbiological analysis of sanitized surfaces were made after 20 minutes and 48 hours for the hot cell of Tc-99m and 72 hours for the hot cell of EDTMP Sm-153 in 3 consecutive tests by the method of direct contact with plates containing culture medium, made for each sampling point (6 in the first and five in the second). The results showed that the microbial load on surfaces sanitized was below acceptable limits and that the lifetime of cleaning and sanitization is 48 hours for the hot cell of Tc-99m and 72 hours for the one of EDTMP-Sm-153. As a conclusion, the method of cleaning and sanitization is effective to reduce or eliminate microbial contamination therefore, the process is validated. (authors).

  18. RP-HPLC method development and validation for estimation of rivaroxaban in pharmaceutical dosage forms

    Directory of Open Access Journals (Sweden)

    Mustafa Çelebier

    2013-06-01

    Full Text Available Rivaroxaban, an anti-clotting medication, acts at a crucial point in the blood-clotting process and stops the formation of blood clots. In this study, RP-HPLC method was developed for the determination of rivaroxaban in tablets (Xarelto® (10 mg. Phenomenex Luna 5 µm C18 100 Å LC Column (250 x 4.6 mm was used at 40 ºC. Isocratic elution was performed with ACN:Water (55:45 v/v mixture. The flow rate was 1.2 mL min-1 and UV detection was at 249 nm. Internal standard (Caffeine and rivaroxaban were eluted within 2.21 and 3.37 minutes, respectively. The developed method was validated according to the ICH guidelines and found to be linear within the range 0.005 - 40.0 µg mL-1. The method was accurate, precise, robust and rapid. Thus, it was applied successfully for the quality control assay of rivaroxaban in tablet dosage form.

  19. Development and validation of a Q-PCR based TCID50 method for human herpesvirus 6

    Directory of Open Access Journals (Sweden)

    Gustafsson Rasmus K L

    2012-12-01

    Full Text Available Abstract Background For titer assessment of human herpesvirus 6 (HHV-6, IFA targeting viral proteins or a TCID50 method with ocular inspection for CPE can be used. These methods rely on the subjective decision of the assessor, obstructing the ability to obtain unanimous results. Findings We have developed and validated an alternative TCID50 read-out approach where infection in the titration culture plate is assessed by viral DNA load change by quantitative PCR. A ten time increase in viral DNA load was determined as cut point for infection since that yielded a maximum correlation with viral protein expression (93%. The average intra-assay CV was 9% for quantitative PCR read-out of TCID50 compared to 45% for ocular inspection read-out of TCID50, 14% for IFA read-out of TCID50, and 43% for an infectious units approach using IFA. The average inter-assay CV for quantitative PCR read-out of TCID50 was 73%, compared to 66%, 25% and 77% for the ocular inspection read-out for TCID50, IFA read-out of TCID50 and infectious unit approaches respectively. Conclusions The quantitative PCR based read-out of TCID50 proved to be more robust and easier to interpret than traditional TCID50 assessment approaches for HHV-6, and therefore it might be considered as an alternative method.

  20. Validation of a liquid chromatographic method for the pharmaceutical quality control of products containing elacridar

    Directory of Open Access Journals (Sweden)

    Emilia Sawicki

    2016-08-01

    Full Text Available Many anticancer drugs have an impaired bioavailability and poor brain penetration because they are substrates to drug efflux pumps such as P-glycoprotein and Breast Cancer Resistance Protein. Elacridar is a strong inhibitor of these two drug efflux pumps and therefore has great potential to improve oral absorption and brain penetration of many anticancer drugs. Currently, a clinical formulation of elacridar is unavailable and therefore the pharmaceutical development of a drug product is highly warranted. This also necessitates the availability of an analytical method for its quality control. A reverse-phase high-performance liquid chromatographic method with ultraviolet detection was developed for the pharmaceutical quality control of products containing elacridar as the active pharmaceutical ingredient. The analytical method was validated for linearity, accuracy, precision, selectivity, carry-over, stability of stock and reference solutions, stability of the final extract, stability-indicating capability and impurity testing. We found that elacridar is unstable in aqueous solutions that are exposed to light because a hydroxylation product of elacridar is formed. Therefore, sample solutions with elacridar must be protected from light.