Sm isotope composition and Sm/Eu ratio determination in an irradiated 153Eu sample by ion exchange chromatography-quadrupole inductively coupled plasma mass spectrometry combined with double spike isotope dilution technique

International Nuclear Information System (INIS)

Bourgeois, M.; Isnard, H.; Gourgiotis, A.; Stadelmann, G.; Gautier, C.; Mialle, S.; Nonell, A.; Chartier, F.

2011-01-01

Within the framework of the research undertaken by the French Atomic Energy Commission on transmutation of long-lived radionuclides, targets of highly enriched actinides and fission products were irradiated in the fast neutron reactor Phenix. Precise and accurate measurements of the isotopic and elemental composition of the enriched elements are therefore required. In order to obtain the uncertainties of several per mil and to reduce handling time and exposure to analyst on radioactive material, the on-line coupling of ion exchange chromatography with quadrupole inductively coupled plasma mass spectrometry has been associated with the technique of the double spike isotope dilution. We present in this paper the results obtained on an irradiated sample of Europium oxide powder (enriched at 99.13% in 153 Eu). After irradiation of around 5 mg of Eu 2 O 3 powder the theoretical calculations predict the formation of several micrograms of gadolinium and samarium isotopes. In relation to the very high activity of the sample after irradiation and the very low quantity of Sm formed, the on-line ion exchange chromatography separation of Gd, Sm and Eu before Sm isotope ratio measurements has been developed for the quantification of the 152 Sm/ 153 Eu ratio. These on-line measurements were associated with the double spike isotope dilution technique after calibration of a 147 Sm/ 151 Eu spike solution. The external reproducibility of Sm isotopic ratios was determined to be around 0.5% (2 σ) resulting in a final uncertainty on the 152 Sm/ 153 Eu ratio of around 1% (2 σ). These on-line measurements present therefore a robust and high-throughput alternative to the thermal-ionisation mass spectrometry technique used so far in combination with off-line chromatographic separation, particularly in nuclear applications where characterisation of high activity sample solutions is required. (authors)

Total cholesterol in serum determined by isotope dilution/mass spectrometry, with liquid-chromatographic separation

International Nuclear Information System (INIS)

Takatsu, Akiko; Nishi, Sueo

1988-01-01

We describe an accurate, precise method for determination of total serum cholesterol by isotope dilution/mass spectrometry (IDMS) with liquid chromatographic separation. After adding [3,4- 13 C] cholesterol to serum and hydrolyzing the cholesterol esters, we extract the total cholesterol. High-performance liquid chromatography (HPLC) is used to separate the extracted cholesterol for measurement by electron-impact mass spectrometry with use of a direct-insertion device. To evaluate the specificity and the accuracy of this method, we also studied the conventional IDMS method, which involves converting cholesterol to the trimethylsilyl ether and assay by gas chromatography-mass spectrometry with use of a capillary column. The coefficient of variation for the HPLC method was a little larger than for the conventional method, but mean values by each method agreed within 1% for all sera tested. (author)

Determination of Dibutyltin in Sediments Using Isotope Dilution Liquid Chromatography-Inductively Coupled Plasma Mass Spectrometry

International Nuclear Information System (INIS)

Yim, Yong Hyeon; Park, Ji Youn; Han, Myung Sub; Park, Mi Kyung; Kim, Byung Joo; Lim, Young Ran; Hwang, Eui Jin; So, Hun Young

2005-01-01

A method is described for the determination of dibutyltin (DBT) in sediment by isotope dilution using liquid chromatography inductively-coupled plasma/mass spectrometry (LC-ICP/MS). To achieve the highest accuracy and precision, special attentions are paid in optimization and evaluation of overall processes of the analysis including extraction of analytes, characterization of the standards used for calibration and LC-ICP/MS conditions. An approach for characterization of natural abundance DBT standard has been developed by combining inductively-coupled plasma/optical emission spectrometry (ICP/OES) and LC-ICP/MS for the total Sn assay and the analysis of Sn species present as impurities, respectively. An excellent LC condition for separation of organotin species was found, which is suitable for simultaneous DBT and tributyltin (TBT) analysis as well as impurity analysis of DBT standards. Microwave extraction condition was also optimized for high efficiency while preventing species transformation. The present method determines the amount contents of DBT in sediments with expanded uncertainty of less than 5% and its result shows high degree of equivalence with reference values of an international inter-comparison and a certified reference material (CRM) within stated uncertainties

Determination of Dibutyltin in Sediments Using Isotope Dilution Liquid Chromatography-Inductively Coupled Plasma Mass Spectrometry

Energy Technology Data Exchange (ETDEWEB)

Yim, Yong Hyeon; Park, Ji Youn; Han, Myung Sub; Park, Mi Kyung; Kim, Byung Joo; Lim, Young Ran; Hwang, Eui Jin; So, Hun Young [Korea Research Institute of Standards and Science, Daejeon (Korea, Republic of)

2005-03-15

A method is described for the determination of dibutyltin (DBT) in sediment by isotope dilution using liquid chromatography inductively-coupled plasma/mass spectrometry (LC-ICP/MS). To achieve the highest accuracy and precision, special attentions are paid in optimization and evaluation of overall processes of the analysis including extraction of analytes, characterization of the standards used for calibration and LC-ICP/MS conditions. An approach for characterization of natural abundance DBT standard has been developed by combining inductively-coupled plasma/optical emission spectrometry (ICP/OES) and LC-ICP/MS for the total Sn assay and the analysis of Sn species present as impurities, respectively. An excellent LC condition for separation of organotin species was found, which is suitable for simultaneous DBT and tributyltin (TBT) analysis as well as impurity analysis of DBT standards. Microwave extraction condition was also optimized for high efficiency while preventing species transformation. The present method determines the amount contents of DBT in sediments with expanded uncertainty of less than 5% and its result shows high degree of equivalence with reference values of an international inter-comparison and a certified reference material (CRM) within stated uncertainties.

Isotope Dilution - Thermal Ionisation Mass Spectrometric Analysis for Tin in a Fly Ash Material

International Nuclear Information System (INIS)

Hernandez, C.; Fernandez, M.; Quejido, A. L.

2006-01-01

Isotope dilution-thermal ionisation mass spectrometry (ID-TIMS) analysis has been applied to the determination of tin in a fly ash sample supplied by the EC Joint Research Centre (Ispra, Italy). The proposed procedure includes the silica gel/phosphoric acid technique for tin thermal ionisation activation and a strict heating protocol for isotope ratio measurements. Instrumental mass discrimination factor has been previously determined measuring a natural tin standard solution. Spike solutions has been prepared from 112Sn-enriched metal and quantified by reverse isotope dilution analysis. Two sample aliquots were spiked and tin was extracted with 4,5 M HCI during 25 min ultrasound esposure time. Due to the complex matrix of this fly ash material, a two-steps purification stage using ion-exchange chromatography was required prior TIMS analysis. Obtained results for the two sample-spike blends (10,10 + - 0,55 y 10,50 + - 0,64 imolg-1) are comprarable, both value and uncertainty. Also a good reproducibility is observed between measurements. The proposed ID-TIMS procedure, as a primary method and due to the lack of fly ash reference material certified for tin content, can be used to validate more routine methodologies applied to tin determination in this kind of materials. (Author) 75 refs

Gas chromatography/ion trap mass spectrometry applied for the analysis of triazine herbicides in environmental waters by an isotope dilution technique

International Nuclear Information System (INIS)

Cai Zongwei; Wang Dongli; Ma, W.T.

2004-01-01

A gas chromatography/ion trap mass spectrometry method was developed for the analysis of simazine, atrazine, cyanazine, as well as the degradation products of atrazine, such as deethylatrazine and deisopropylatrazine in environmental water samples. Isotope dilution technique was applied for the quantitative analysis of atrazine in water at low ng/l levels. One liter of water sample spiked with stable isotope internal standard atrazine-d 5 was extracted with a C 18 solid-phase extraction cartridge. The analysis was performed on an ion trap mass spectrometer operated in MS/MS method. The extraction recoveries were in the range of 83-94% for the triazine herbicides in water at the concentrations of 24, 200, and 1000 ng/l, while poor recoveries were obtained for the degradation products of atrazine. The relative standard deviation (R.S.D.) were within the range of 3.2-16.1%. The detection limits of the method were between 0.75 and 12 ng/l when 1 l of water was analyzed. The method was successfully applied to analyze environmental water samples collected from a reservoir and a river in Hong Kong for atrazine detected at concentrations between 3.4 and 26 ng/l

Isotope dilution mass spectrometry: some present limitations and possibilities to overcome these

International Nuclear Information System (INIS)

De Bievre, P.

1981-01-01

Thermionic mass spectrometry still has great potential for more precise and accurate measurements but it is going to place tremendous requirements on (1) the chemical purity of the samples we measure, (2) the temperature of both ionization and the filaments and (3) the number of molecular species being handled in ion sources which could increase to several dozen for one type of isotopic analysis. The lack of control by mass spectrometrists over the chemical preparation of the samples for isotopic analysis is an inherent limitation to further improvement of isotope dilution mass spectrometry. A limiting factor in isotope dilution is the ability to measure the ratio. At present, uranium isotopic reference materials are 0.1% and recently one was prepared at 0.05%. As these serve to calibrate isotope ratio measurements one cannot do better than these valves. There is no way in which isotope dilution can be improved until these reference values improve. For plutonium there are not even absolute isotope ratio standards. An agreement has been established between CBNM, Geel and the National Bureau of Standards, Washington, to prepare isotope ratio reference materials jointly so that they will be common to both communities. It is recommended that common batches of reference be established and stored at several places to guarantee accessibility at all times

Determination of Glyphosate, its Degradation Product Aminomethylphosphonic Acid, and Glufosinate, in Water by Isotope Dilution and Online Solid-Phase Extraction and Liquid Chromatography/Tandem Mass Spectrometry

Science.gov (United States)

Meyer, Michael T.; Loftin, Keith A.; Lee, Edward A.; Hinshaw, Gary H.; Dietze, Julie E.; Scribner, Elisabeth A.

2009-01-01

The U.S. Geological Survey method (0-2141-09) presented is approved for the determination of glyphosate, its degradation product aminomethylphosphonic acid (AMPA), and glufosinate in water. It was was validated to demonstrate the method detection levels (MDL), compare isotope dilution to standard addition, and evaluate method and compound stability. The original method USGS analytical method 0-2136-01 was developed using liquid chromatography/mass spectrometry and quantitation by standard addition. Lower method detection levels and increased specificity were achieved in the modified method, 0-2141-09, by using liquid chromatography/tandem mass spectrometry (LC/MS/MS). The use of isotope dilution for glyphosate and AMPA and pseudo isotope dilution of glufosinate in place of standard addition was evaluated. Stable-isotope labeled AMPA and glyphosate were used as the isotope dilution standards. In addition, the stability of glyphosate and AMPA was studied in raw filtered and derivatized water samples. The stable-isotope labeled glyphosate and AMPA standards were added to each water sample and the samples then derivatized with 9-fluorenylmethylchloroformate. After derivatization, samples were concentrated using automated online solid-phase extraction (SPE) followed by elution in-line with the LC mobile phase; the compounds separated and then were analyzed by LC/MS/MS using electrospray ionization in negative-ion mode with multiple-reaction monitoring. The deprotonated derivatized parent molecule and two daughter-ion transition pairs were identified and optimized for glyphosate, AMPA, glufosinate, and the glyphosate and AMPA stable-isotope labeled internal standards. Quantitative comparison between standard addition and isotope dilution was conducted using 473 samples analyzed between April 2004 and June 2006. The mean percent difference and relative standard deviation between the two quantitation methods was 7.6 plus or minus 6.30 (n = 179), AMPA 9.6 plus or minus 8

Simultaneous analysis of polychlorinated biphenyls and polychlorinated naphthalenes by isotope dilution comprehensive two-dimensional gas chromatography high-resolution time-of-flight mass spectrometry

International Nuclear Information System (INIS)

Xia, Dan; Gao, Lirong; Zheng, Minghui; Wang, Shasha; Liu, Guorui

2016-01-01

Polychlorinated biphenyls (PCBs) and polychlorinated naphthalenes (PCNs) are listed as persistent organic pollutants (POPs) under the Stockholm Convention. Because they have similar physical and chemical properties, they are coeluted and are usually analyzed separately by different gas chromatography high-resolution mass spectrometry (GC-HRMS) methods. In this study, a novel method was developed for simultaneous analysis of six indicator PCBs, 12 dioxin-like PCBs, and 16 PCNs using isotope dilution comprehensive two-dimensional gas chromatography with high-resolution time-of-flight mass spectrometry (GC × GC-HRTOF-MS). The method parameters, including the type of GC column, oven temperature program, and modulation period, were systematically optimized. Complete separation of all target analytes and the matrix was achieved with a DB-XLB column in the first dimension and a BPX-70 column in the second dimension. The isotope dilution method was used for quantification of the PCBs and PCNs by GC × GC-HRTOF-MS. The method showed good linearity from 5 to 500 pg μL"−"1 for all the target compounds. The instrumental limit of detection ranged from 0.03 to 0.3 pg μL"−"1 for the 18 PCB congeners and from 0.09 to 0.6 pg μL"−"1 for the 16 PCN congeners. Repeatability for triplicate injections was always lower than 20%. The method was successfully applied to the determination of 18 PCBs present at 0.9–2054 pg g"−"1 and 16 PCNs present at 0.2–15.7 pg g"−"1 in three species of fish. The GC × GC-HRTOF-MS results agreed with those obtained by GC-HRMS. The GC × GC-HRTOF-MS method proved to be a sensitive and accurate technique for simultaneous analysis of the selected PCBs and PCNs. With the excellent chromatographic separation offered by GC × GC and accurate mass measurements offered by HRTOF-MS, this method allowed identification of non-target contaminants in the fish samples, including organochlorine pesticides and polycyclic aromatic

Simultaneous analysis of polychlorinated biphenyls and polychlorinated naphthalenes by isotope dilution comprehensive two-dimensional gas chromatography high-resolution time-of-flight mass spectrometry

Energy Technology Data Exchange (ETDEWEB)

Xia, Dan [State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085 (China); University of Chinese Academy of Sciences, Beijing 100085 (China); Gao, Lirong, E-mail: gaolr@rcees.ac.cn [State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085 (China); Zheng, Minghui; Wang, Shasha; Liu, Guorui [State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085 (China)

2016-09-21

Polychlorinated biphenyls (PCBs) and polychlorinated naphthalenes (PCNs) are listed as persistent organic pollutants (POPs) under the Stockholm Convention. Because they have similar physical and chemical properties, they are coeluted and are usually analyzed separately by different gas chromatography high-resolution mass spectrometry (GC-HRMS) methods. In this study, a novel method was developed for simultaneous analysis of six indicator PCBs, 12 dioxin-like PCBs, and 16 PCNs using isotope dilution comprehensive two-dimensional gas chromatography with high-resolution time-of-flight mass spectrometry (GC × GC-HRTOF-MS). The method parameters, including the type of GC column, oven temperature program, and modulation period, were systematically optimized. Complete separation of all target analytes and the matrix was achieved with a DB-XLB column in the first dimension and a BPX-70 column in the second dimension. The isotope dilution method was used for quantification of the PCBs and PCNs by GC × GC-HRTOF-MS. The method showed good linearity from 5 to 500 pg μL{sup −1} for all the target compounds. The instrumental limit of detection ranged from 0.03 to 0.3 pg μL{sup −1} for the 18 PCB congeners and from 0.09 to 0.6 pg μL{sup −1} for the 16 PCN congeners. Repeatability for triplicate injections was always lower than 20%. The method was successfully applied to the determination of 18 PCBs present at 0.9–2054 pg g{sup −1} and 16 PCNs present at 0.2–15.7 pg g{sup −1} in three species of fish. The GC × GC-HRTOF-MS results agreed with those obtained by GC-HRMS. The GC × GC-HRTOF-MS method proved to be a sensitive and accurate technique for simultaneous analysis of the selected PCBs and PCNs. With the excellent chromatographic separation offered by GC × GC and accurate mass measurements offered by HRTOF-MS, this method allowed identification of non-target contaminants in the fish samples, including organochlorine pesticides and

Rapid and precise measurement of serum branched-chain and aromatic amino acids by isotope dilution liquid chromatography tandem mass spectrometry.

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Ruiyue Yang

Full Text Available BACKGROUND: Serum branched-chain and aromatic amino acids (BCAAs and AAAs have emerged as predictors for the future development of diabetes and may aid in diabetes risk assessment. However, the current methods for the analysis of such amino acids in biological samples are time consuming. METHODS: An isotope dilution liquid chromatography tandem mass spectrometry (ID-LC/MS/MS method for serum BCAAs and AAAs was developed. The serum was mixed with isotope-labeled BCAA and AAA internal standards and the amino acids were extracted with acetonitrile, followed by analysis using LC/MS/MS. The LC separation was performed on a reversed-phase C18 column, and the MS/MS detection was performed via the positive electronic spray ionization in multiple reaction monitoring mode. RESULTS: Specific analysis of the amino acids was achieved within 2 min. Intra-run and total CVs for the amino acids were less than 2% and 4%, respectively, and the analytical recoveries ranged from 99.6 to 103.6%. CONCLUSION: A rapid and precise method for the measurement of serum BCAAs and AAAs was developed and may serve as a quick tool for screening serum BCAAs and AAAs in studies assessing diabetes risk.

Determination of zinc stable isotopes in biological materials using isotope dilution inductively coupled plasma mass spectrometry

International Nuclear Information System (INIS)

Patterson, K.Y.; Veillon, Claude

1992-01-01

A method is described for using isotope dilution to determine both the amount of natural zinc and enriched isotopes of zinc in biological samples. Isotope dilution inductively coupled plasma mass spectrometry offers a way to quantify not only the natural zinc found in a sample but also the enriched isotope tracers of zinc. Accurate values for the enriched isotopes and natural zinc are obtained by adjusting the mass count rate data for measurable instrumental biases. Analytical interferences from the matrix are avoided by extracting the zinc from the sample matrix using diethylammonium diethyldithiocarbamate. The extraction technique separates the zinc from elements which form interfering molecular ions at the same nominal masses as the zinc isotopes. Accuracy of the method is verified using standard reference materials. The detection limit is 0.06 μg Zn per sample. Precision of the abundance ratios range from 0.3-0.8%. R.S.D. for natural zinc concentrations is about 200-600 μg g -1 . The accuracy and precision of the measurements make it possible to follow enriched isotopic tracers of zinc in biological samples in metabolic tracer studies. (author). 19 refs.; 1 fig., 4 tabs

A double isotope dilution method for assaying of polycyclic aromatic hydrocarbons in cigarette smoke condensate

International Nuclear Information System (INIS)

Bechtold, W.E.; Chen, B.T.

1988-01-01

This report describes a double isotope dilution method for analysis of the polycyclic aromatic hydrocarbons (PAH) phenanthrene, fluor-anthene, pyrene, and benzo[a]pyrene in cigarette smoke particulates. The first isotope dilution used deuterated analogues of the first three PAH as internal standards. The second isotope dilution, for benzo[a]pyrene, used the tritiated analogue as an internal standard. The PAH were isolated from extracts of cigarette smoke particulates using a two-step procedure based on selective extraction from aqueous dimethyl sulfoxide (DMSO) followed by chromatography on silica gel extraction columns. After isolation, aliquots of the samples were analyzed for phenanthrene, pyrene, and fluoranthene by gas chromatography with mass spectrometric detection (GC/MS). Separate aliquots of the samples were analyzed for benzo[a]pyrene by high pressure liquid chromatography with fluorescence detection followed by liquid scintillation spectrometry. PAH levels from cigarette smoke condensates collected from different exposure modes were compared; no exposure-related differences were found. (author)

Development of multi-residue method for the determination of pesticides in cereal matrices by isotopic dilution associated to liquid chromatography coupled to tandem mass spectrometry after pressurized liquid extraction

International Nuclear Information System (INIS)

El Mrabet, Khadija

2008-01-01

Pesticides are nowadays considered as toxic for human health. The maximal residues levels authorized in water and foodstuff are more and more strict. Therefore, selective analytical techniques are necessary for their identification and their quantification. The aim of this thesis was to develop a multi-residue method for the determination of pesticides by isotopic dilution associated to liquid chromatography (LC) coupled with tandem mass spectrometry (MS"2) after pressurized liquid extraction. In a first step, an analysis method of phenyl-ureas and triazines in groundwater by isotopic dilution associated to LC/MS"2 after solid phase extraction has been developed. The method has been validated and evaluated by participating to an inter-laboratory study. Concerning cereals, an extraction method of pesticides associated to an analysis by LC/MS"2 has been developed for thirty-eight pesticides representative of twenty-six chemicals families and fourteen labeled compounds in wheat. The analysis has been carried out in reversed phase chromatography. Separation and detection conditions have been optimized. A global analytical protocol consisting of a pressurized liquid extraction step using acetonitrile at 100 deg. C and at 100 bars and followed by purification step of the resulting extract on a polymeric sorbent was developed. The developed method enables to extract thirty-eight pesticides and fourteen labeled compounds from wheat with recovery yield about 85% (RSD =4%, n=3). Moreover, the results show that the application of isotopic dilution can be complex. Although some improvements need to be added regarding experimentation of aged matrices or contaminated samples, the potential of the method has been demonstrated. (author) [fr

Evaluation of online carbon isotope dilution mass spectrometry for the purity assessment of synthetic peptide standards

Energy Technology Data Exchange (ETDEWEB)

Díaz, Sergio Cueto; Ruiz Encinar, Jorge, E-mail: ruizjorge@uniovi.es; García Alonso, J. Ignacio, E-mail: jiga@uniovi.es

2014-09-24

Highlights: • Purity assessment of peptide standards applicable to any water soluble peptide. • Online {sup 13}C isotope dilution mass spectrometry. • Mass flow chromatogram from measured 44/45 isotope ratios. • Validation by the analysis of NIST 8327. - Abstract: We present a novel method for the purity assessment of peptide standards which is applicable to any water soluble peptide. The method is based on the online {sup 13}C isotope dilution approach in which the peptide is separated from its related impurities by liquid chromatography (LC) and the eluent is mixed post-column with a continuous flow of {sup 13}C-enriched sodium bicarbonate. An online oxidation step using sodium persulfate in acidic media at 99 °C provides quantitative oxidation to {sup 12}CO{sub 2} and {sup 13}CO{sub 2} respectively which is extracted to a gaseous phase with the help of a gas permeable membrane. The measurement of the isotope ratio 44/45 in the mass spectrometer allows the construction of the mass flow chromatogram. As the only species that is finally measured in the mass spectrometer is CO{sub 2}, the peptide content in the standard can be quantified, on the base of its carbon content, using a generic primary standard such as potassium hydrogen phthalate. The approach was validated by the analysis of a reference material (NIST 8327), and applied to the quantification of two commercial synthetic peptide standards. In that case, the results obtained were compared with those obtained using alternative methods, such as amino acid analysis and ICP-MS. The results obtained proved the value of the method for the fast, accurate and precise mass purity assignment of synthetic peptide standards.

An improved reference measurement procedure for triglycerides and total glycerides in human serum by isotope dilution gas chromatography-mass spectrometry.

Science.gov (United States)

Chen, Yizhao; Liu, Qinde; Yong, Sharon; Teo, Hui Ling; Lee, Tong Kooi

2014-01-20

Triglycerides are widely tested in clinical laboratories using enzymatic methods for lipid profiling. As enzymatic methods can be affected by interferences from biological samples, this together with the non-specific nature of triglycerides measurement makes it necessary to verify the accuracy of the test results with a reference measurement procedure. Several such measurement procedures had been published. These procedures generally involved lengthy and laborious sample preparation steps. In this paper, an improved reference measurement procedure for triglycerides and total glycerides was reported which simplifies the sample preparation steps and greatly shortens the time taken. The procedure was based on isotope dilution gas chromatography-mass spectrometry (IDGC-MS)with tripalmitin as the calibration standard. Serum samples were first spiked with isotope-labeled tripalmitin. For the measurement of triglycerides, the serum samples were subjected to lipid extraction followed by separation of triglycerides from diglycerides and monoglycerides. Triglycerides were then hydrolyzed to glycerol, derivatized and injected into the GC–MS for quantification. For the measurement of total glycerides, the serum samples were hydrolyzed directly and derivatized before injection into the GC-MS for quantification. All measurement results showed good precision with CV triglycerides and total glycerides were well within the certified ranges of the CRM, with deviation triglycerides and total glycerides.

Determination of thyroid hormones in mouse tissues by isotope-dilution microflow liquid chromatography-mass spectrometry method.

Science.gov (United States)

De Angelis, Meri; Giesert, Florian; Finan, Brian; Clemmensen, Christoffer; Müller, Timo D; Vogt-Weisenhorn, Daniela; Tschöp, Matthias H; Schramm, Karl-Werner

2016-10-15

Thyroid hormones (THs) play a critical role in the regulation of many biological processes such as growth, metabolism and development both in humans and wildlife. In general, TH levels are measured by immunoassay (IA) methods but the specificity of the antibodies used in these assays limits selectivity. In the last decade, several analytical methods using liquid chromatography-mass spectrometry (LC-MS) and tandem mass spectrometry (LC-MS/MS) have been developed to measure THs. These new techniques proved to be more accurate than the IA analysis and they were widely used for the determination of TH level in different human and animal tissues. A large part of LC-MS/MS methods described in literature employed between 200 and 500mg of sample, however this quantity can be considered too high especially when preclinical studies are conducted using mice as test subjects. Thus an analytical method that reduces the amount of tissue is essential. In this study, we developed a procedure for the analysis of six THs; L-thyroxine (T4), 3,3',5-triiodo-l-thyronine (T3), 3,3',5'-triiodo-l-thyronine (rT3), 3,5-diiodo-l-thyronine (rT2), 3,3'-diiodo-l-thyronine (T2), 3-iodo-l-thyronine (T1) using isotope ((13)C6-T4, (13)C6-T3, (13)C6-rT3, (13)C6-T2) dilution liquid chromatography-mass spectrometry. The major difference with previously described methods lies in the utilization of a nano-UPLC (Ultra Performance Liquid Chromatography) system in micro configuration. This approach leads to a reduction compared to the published methods, of column internal diameter, flow rate, and injected volume. The result of all these improvements is a decrease in the amount of sample necessary for the analysis. The method was tested on six different mouse tissues: liver, heart, kidney, muscle, lung and brown adipose tissue (BAT). The nano-UPLC system was interfaced with a quadrupole time-of-flight mass spectrometer (Q-TOF2-MS) using the positive ion mode electrospray ionization. In our analytical method

Detection of triclocarban and two co-contaminating chlorocarbanilides in US aquatic environments using isotope dilution liquid chromatography tandem mass spectrometry

International Nuclear Information System (INIS)

Sapkota, Amir; Heidler, Jochen; Halden, Rolf U.

2007-01-01

The antimicrobial compound triclocarban (TCC; 3,4,4'-trichlorocarbanilide; CAS-bar 101-20-2) is a high-production-volume chemical, recently suggested to cause widespread contamination of US water resources. To test this hypothesis, we developed an isotope dilution liquid chromatography electrospray ionization tandem mass spectrometry method for ultratrace analysis of TCC (0.9ng/L detection limit) and analyzed low-volume water samples (200mL) along with primary sludge samples from across the United States. All river water samples (100%) collected downstream of wastewater treatment plants had detectable levels of TCC, as compared to 56% of those taken upstream. Concentrations of TCC (mean+/-standard deviation) downstream of sewage treatment plants (84+/-110ng/L) were significantly higher (P w/w each) in technical grade TCC (99%). Application of the new method for chlorocarbanilide analysis yielded TCC occurrence data for 13 US states, confirmed the role of sewage treatment plants as environmental inputs of TCC, and identified DCC and TetraCC as previously unrecognized pollutants released into the environment alongside TCC

Hot vacuum extraction-isotopic dilution mass spectrometry for determination of hydrogen isotopes in zircaloys

International Nuclear Information System (INIS)

Shi, Y.; Leeson, P.K.; Wilkin, D.; Britton, A.; Macleod, R.

2016-01-01

A hot vacuum extraction-isotope dilution mass spectrometry (HVE-IDMS) was studied for determination of hydrogen isotopes in zirconium metal and alloys as nuclear reactor materials. A theoretical assessment of the completeness of the extraction of hydrogen isotopes under the chosen condition was carried out based on the hydrogen and deuterium solubility data for zirconium. The optimal isotopic spiking condition for conventional IDMS was further explored for the special case IDMS where the isotope abundance of the samples is varied and non-natural. Applying the optimal conditions, the accurate IDMS determination was realized. The agreement between the measured values and the certified or prepared values of standard reference materials and homemade standard materials validate the method developed. (author)

Determination of bisphenol A, triclosan and their metabolites in human urine using isotope-dilution liquid chromatography-tandem mass spectrometry.

Science.gov (United States)

Provencher, Gilles; Bérubé, René; Dumas, Pierre; Bienvenu, Jean-François; Gaudreau, Eric; Bélanger, Patrick; Ayotte, Pierre

2014-06-27

Bisphenol A (BPA) and triclosan (TCS) are ubiquitous environmental phenols exhibiting endocrine disrupting activities that may be involved in various health disorders in humans. There is a need to measure separately free forms and conjugated metabolites because only the former are biologically active. We have developed sensitive methods using isotope-dilution liquid chromatography-tandem mass spectrometry for individual measurements of free BPA and TCS as well as their metabolites, BPA glucuronide (BPAG), BPA monosulfate (BPAS), BPA disulfate (BPADS), TCS glucuronide (TCSG) and TCS sulfate (TCSS) in urine. Comparative analyses of urine samples from 46 volunteers living in the Quebec City area using the new methods and a GC-MS/MS method previously used in our laboratory revealed very strong correlations for total BPA (Spearman's rs=0.862, purine samples (>94% of total urinary concentrations). Unconjugated TCS concentrations represented a small proportion of total TCS species (median=1.6%) but its concentration was likely underestimated due to losses by adsorption to the surface of polypropylene tubes used for sample storage. To our knowledge, we are the first to report levels of free, sulfated and glucuronidated TCS levels in human urine. Copyright © 2014 Elsevier B.V. All rights reserved.

Cellular Lipid Extraction for Targeted Stable Isotope Dilution Liquid Chromatography-Mass Spectrometry Analysis

Science.gov (United States)

Gelhaus, Stacy L.; Mesaros, A. Clementina; Blair, Ian A.

2011-01-01

The metabolism of fatty acids, such as arachidonic acid (AA) and linoleic acid (LA), results in the formation of oxidized bioactive lipids, including numerous stereoisomers1,2. These metabolites can be formed from free or esterified fatty acids. Many of these oxidized metabolites have biological activity and have been implicated in various diseases including cardiovascular and neurodegenerative diseases, asthma, and cancer3-7. Oxidized bioactive lipids can be formed enzymatically or by reactive oxygen species (ROS). Enzymes that metabolize fatty acids include cyclooxygenase (COX), lipoxygenase (LO), and cytochromes P450 (CYPs)1,8. Enzymatic metabolism results in enantioselective formation whereas ROS oxidation results in the racemic formation of products. While this protocol focuses primarily on the analysis of AA- and some LA-derived bioactive metabolites; it could be easily applied to metabolites of other fatty acids. Bioactive lipids are extracted from cell lysate or media using liquid-liquid (l-l) extraction. At the beginning of the l-l extraction process, stable isotope internal standards are added to account for errors during sample preparation. Stable isotope dilution (SID) also accounts for any differences, such as ion suppression, that metabolites may experience during the mass spectrometry (MS) analysis9. After the extraction, derivatization with an electron capture (EC) reagent, pentafluorylbenzyl bromide (PFB) is employed to increase detection sensitivity10,11. Multiple reaction monitoring (MRM) is used to increase the selectivity of the MS analysis. Before MS analysis, lipids are separated using chiral normal phase high performance liquid chromatography (HPLC). The HPLC conditions are optimized to separate the enantiomers and various stereoisomers of the monitored lipids12. This specific LC-MS method monitors prostaglandins (PGs), isoprostanes (isoPs), hydroxyeicosatetraenoic acids (HETEs), hydroxyoctadecadienoic acids (HODEs), oxoeicosatetraenoic

Comparison of gas chromatography/isotope ratio mass spectrometry and liquid chromatography/isotope ratio mass spectrometry for carbon stable-isotope analysis of carbohydrates.

Science.gov (United States)

Moerdijk-Poortvliet, Tanja C W; Schierbeek, Henk; Houtekamer, Marco; van Engeland, Tom; Derrien, Delphine; Stal, Lucas J; Boschker, Henricus T S

2015-07-15

We compared gas chromatography/isotope ratio mass spectrometry (GC/IRMS) and liquid chromatography/isotope ratio mass spectrometry (LC/IRMS) for the measurement of δ(13)C values in carbohydrates. Contrary to GC/IRMS, no derivatisation is needed for LC/IRMS analysis of carbohydrates. Hence, although LC/IRMS is expected to be more accurate and precise, no direct comparison has been reported. GC/IRMS with the aldonitrile penta-acetate (ANPA) derivatisation method was compared with LC/IRMS without derivatisation. A large number of glucose standards and a variety of natural samples were analysed for five neutral carbohydrates at natural abundance as well as at (13)C-enriched levels. Gas chromatography/chemical ionisation mass spectrometry (GC/CIMS) was applied to check for incomplete derivatisation of the carbohydrate, which would impair the accuracy of the GC/IRMS method. The LC/IRMS technique provided excellent precision (±0.08‰ and ±3.1‰ at natural abundance and enrichment levels, respectively) for the glucose standards and this technique proved to be superior to GC/IRMS (±0.62‰ and ±19.8‰ at natural abundance and enrichment levels, respectively). For GC/IRMS measurements the derivatisation correction and the conversion of carbohydrates into CO2 had a considerable effect on the measured δ(13)C values. However, we did not find any significant differences in the accuracy of the two techniques over the full range of natural δ(13)C abundances and (13)C-labelled glucose. The difference in the performance of GC/IRMS and LC/IRMS diminished when the δ(13)C values were measured in natural samples, because the chromatographic performance and background correction became critical factors, particularly for LC/IRMS. The derivatisation of carbohydrates for the GC/IRMS method was complete. Although both LC/IRMS and GC/IRMS are reliable techniques for compound-specific stable carbon isotope analysis of carbohydrates (provided that derivatisation is complete and the

Optimal sample to tracer ratio for isotope dilution mass spectrometry: the polyisotopic case

International Nuclear Information System (INIS)

Laszlo, G.; Ridder, P. de; Goldman, A.; Cappis, J.; Bievre, P. de

1991-01-01

The Isotope Dilution Mass Spectrometry (IDMS) measurement technique provides a means for determining the unknown amount of various isotopes of an element in a sample solution of known mass. The sample solution is mixed with an auxiliary solution, or tracer, containing a known amount of the same element having the same isotopes but of different relative abundances or isotopic composition and the induced change in the isotopic composition measured by isotope mass spectrometry. The technique involves the measurement of the abundance ratio of each isotope to a (same) reference isotope in the sample solution, in the tracer solution and in the blend of the sample and tracer solution. These isotope ratio measurements, the known element amount in the tracer and the known mass of sample solution are used to calculate the unknown amount of one isotope in the sample solution. Subsequently the unknown amount of element is determined. The purpose of this paper is to examine the optimization of the ratio of the estimated unknown amount of element in the sample solution to the known amount of element in the tracer solution in order to minimize the relative uncertainty in the determination of the unknown amount of element

Determination of trace quantities of uranium in rocks mass spectrometric isotope dilution technique

International Nuclear Information System (INIS)

Kakazu, Mauricio Hiromitu

1980-01-01

A detailed experimental investigation on the thermionic emission of uranium deposited on a single flat type rhenium filament has been carried out. The study was aimed at determining the influence of various forms of deposition on the emission sensitivity and thermal stability of U + , UO + and UO 2 + ions. Based on these investigations, a technique, involving an addition of a small quantity of colloidal suspension of graphite on top of the uranyl nitrate sample deposited, was chosen because of its higher, emission sensitivity for uranium metal ions. The experimental parameters of the technique were optimised and the technique was employed in the determination of trace quantities of uranium in rock samples using mass spectrometric isotope dilution method. For the mass spectrometric isotope dilution analysis National Bureau of Standards uranium isotopic standard NBS-U 970 was employed as a tracer, where as the mass discrimination effect in the uranium isotope analysis was corrected using the uranium isotopic standard NBS-U500. Uranium was determined in each of the seven granite samples from Wyoming, USA and two USGS standard rocks. The precision of the analysis was found to be ±1% . The uranium values obtained on the rock samples were compared with the analyses of other investigators. Influence of the sample splitting on the uranium analysis was discussed in the light of the analytical results obtained.(author)

Thallium determination in reference materials by isotope dilution mass spectrometry (IDMS) using thermal ionization

International Nuclear Information System (INIS)

Waidmann, E.; Hilpert, K.; Stoeppler, M.

1990-01-01

Using Isotope Dilution Mass Spectrometry (IDMS) with thermal ionization, thallium concentrations were determined in reference materials from NIST and BCR, from other sources, and reference materials from the German Environmental Specimen Bank 203 Tl spike solution is applied for the isotope dilution technique. Thallium concentrations in the investigated materials range from 2.67 μg Tl.kg -1 to 963 μg Tl.kg -1 with a relative standard deviation from 0.14 to 10%. The detection limit was 0.1 ng thallium for this work. (orig.)

Isotope-dilution mass spectrometry in the measurement of plutonium isotope half-lives

International Nuclear Information System (INIS)

Abernathey, R.M.; Marsh, S.F.

1981-01-01

Isotope-dilution mass spectrometry has been used at Los Alamos to measure the half-lives of 239 Pu, 240 Pu, and 241 Pu. The latter was determined by measuring the rate of decrease of the 241 Pu/ 242 Pu ratio in an appropriate isotopic mixture over a period of several years. The half-lives of the two lighter isotopes are too long to be determined in this manner. They were determined by measuring the rate of production of the uranium daughter relative to a known added 233 U spike. Experimental procedures were designed to control sources of error and to permit a detailed statistical treatment which included all known sources of error and accounted for all covariances. The uncertainties, at the 95% confidence level, associated with the measured half-lives were less than 0.4% for 241 Pu and less than 0.2% for 239 Pu and 240 Pu

Quantification of 16 polycyclic aromatic hydrocarbons in cigarette smoke condensate using stable isotope dilution liquid chromatography with atmospheric-pressure photoionization tandem mass spectrometry.

Science.gov (United States)

Zhang, Xiaotao; Hou, Hongwei; Chen, Huan; Liu, Yong; Wang, An; Hu, Qingyuan

2015-09-17

A stable isotope dilution liquid chromatography with tandem mass spectrometry method for the analysis of 16 polycyclic aromatic hydrocarbons in cigarette smoke condensate was developed and validated. Compared with previously reported methods, this method has lower limits of detection (0.04-1.35 ng/cig). Additionally, the proposed method saves time, reduces the number of separation steps, and reduces the quantity of solvent needed. The new method was applied to evaluate polycyclic aromatic hydrocarbon content in 213 commercially available cigarettes in China, under the International Standardization Organization smoking regime and the Health Canadian intense smoking regime. The results showed that the total polycyclic aromatic hydrocarbon content was more than two times higher in samples from the Health Canadian intense smoking regime than in samples from the International Standardization Organization smoking regime (1189.23 vs. 2859.50 ng/cig, ppolycyclic aromatic hydrocarbons (and total polycyclic aromatic hydrocarbons) increased with labeled tar content in both of the tested smoking regimes. There was a positive correlation between total polycyclic aromatic hydrocarbons under the International Standardization Organization smoking regime with that under the Health Canadian intense smoking regime. The proposed liquid chromatography with tandem mass spectrometry method is satisfactory for the rapid, sensitive, and accurately quantitative evaluation of polycyclic aromatic hydrocarbon content in cigarette smoke condensate, and it can be applied to assess potential health risks from smoking. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Isotope dilution mass spectrometry for nuclear material accountability measurements: dreams and reality

International Nuclear Information System (INIS)

Deron, S.; )

1996-01-01

Gravimetry, titration, coulometry and isotope dilution mass spectrometry are alternative techniques which can be used to obtain elemental assays of the desirable accuracy. The communication briefly describes the characteristics of the procedure and summarizes a wealth of experience accumulated during actual accountability verification activities

Error analysis of isotope dilution mass spectrometry method with internal standard

International Nuclear Information System (INIS)

Rizhinskii, M.W.; Vitinskii, M.Y.

1989-02-01

The computation algorithms of the normalized isotopic ratios and element concentration by isotope dilution mass spectrometry with internal standard are presented. A procedure based on the Monte-Carlo calculation is proposed for predicting the magnitude of the errors to be expected. The estimation of systematic and random errors is carried out in the case of the certification of uranium and plutonium reference materials as well as for the use of those reference materials in the analysis of irradiated nuclear fuels. 4 refs, 11 figs, 2 tabs

Daily cortisol production rate in man determined by stable isotope dilution/mass spectrometry

International Nuclear Information System (INIS)

Esteban, N.V.; Loughlin, T.; Yergey, A.L.; Zawadzki, J.K.; Booth, J.D.; Winterer, J.C.; Loriaux, D.L.

1991-01-01

Growth retardation as well as the development of Cushingoid features in adrenally insufficient patients treated with the currently accepted replacement dose of cortisol (33-41 mumol/day.m2; 12-15 mg/m2.day) prompted us to reevaluate the cortisol production rate (FPR) in normal subjects and patients with Cushing's syndrome, using a recently developed thermospray liquid chromatography-mass spectrometry method. The stable isotope [9,12,12-2H3]cortisol was infused continuously for 31 h at about 5% of the anticipated FPR. Blood samples were obtained at 20-min intervals for 24 h, spun, and pooled in 4-h groups. Tracer dilution in plasma was determined by liquid chromatography/mass spectrometry. The method was validated with controlled infusions in 6 patients with adrenal insufficiency. Results from 12 normal volunteers revealed a FPR of 27.3 +/- 7.5 mumol/day (9.9 +/- 2.7 mg/day) or 15.7 mumol/day.m2; 5.7 mg/m2. day. A previously unreported circadian variation in FPR was observed. Patients with Cushing's syndrome demonstrated unequivocal elevation of FPR and cortisol concentration correlated during each sample period in normal volunteers, indicating that cortisol secretion, rather than metabolism, is mainly responsible for changes in plasma cortisol. Our data suggest that the FPR in normal subjects may be lower than previously believed

Determination of urea kinetics by isotope dilution with [C-13]urea and gas chromatography isotope ratio mass spectrometry (GC-IRMS) analysis

NARCIS (Netherlands)

Kloppenburg, Wybe; Wolthers, BG; Stellaard, F; Elzinga, H; Tepper, T; deJong, PE; Huisman, RM

1. Stable urea isotopes can be used to study urea kinetics in humans, The use of stable urea isotopes far studying urea kinetic parameters in humans on a large scale is hampered by the high costs of the labelled material, We devised a urea dilution for measurement of the distribution volume,

Development and application of liquid chromatography coupled to isotope ratio mass spectrometry

Energy Technology Data Exchange (ETDEWEB)

Zhang, Lijun

2014-02-19

Stable isotope analysis has found widespread applications in various disciplines such as archaeology, geochemistry, biology, food authenticity, and forensic science. Coupling chromatography to isotope ratio mass spectrometry for compound-specific isotope analysis (CSIA) is a trend, as it provides several advantages over bulk isotope analysis, e.g., relatively simple sample preparation, the ability to measure individual compounds in a complex mixture in one run, and the reduced sample size required for precise isotope analysis. Gas chromatography coupled to isotope ratio mass spectrometry (GC/IRMS) has been well-established for compound-specific isotope analysis of volatile organic compounds within the last two decades. However, an interface combining liquid chromatography with isotope ratio mass spectrometry (LC/IRMS) was not commercially available until 2004. The current design of the interface requires using a carbon-free eluent in chromatographic separation. This requirement limits the application of the most frequently used reversed-phase liquid chromatography in CSIA, because the elution strength of water at room temperature is too low to serve as mobile phase in reversed-phase separations. In order to increase the elution strength of water, we propose using high temperature water for chromatographic elution. The polarity of water decreases with an increase of temperature, yielding increased elution strength in reversed-phase columns. Therefore, high temperature water can be used as eluent instead of organic solvent for combining reversed-phase liquid chromatography with isotope ratio mass spectrometry (RPLC/IRMS). Additionally, temperature gradients can replace organic solvent gradients to increase chromatographic resolution. This is very important for LC/IRMS analysis, as precise isotope analysis requires baseline separation of analytes. In this thesis, high-temperature reversed-phase liquid chromatography was coupled to, and for the first time carefully

Development and application of liquid chromatography coupled to isotope ratio mass spectrometry

International Nuclear Information System (INIS)

Zhang, Lijun

2014-01-01

Stable isotope analysis has found widespread applications in various disciplines such as archaeology, geochemistry, biology, food authenticity, and forensic science. Coupling chromatography to isotope ratio mass spectrometry for compound-specific isotope analysis (CSIA) is a trend, as it provides several advantages over bulk isotope analysis, e.g., relatively simple sample preparation, the ability to measure individual compounds in a complex mixture in one run, and the reduced sample size required for precise isotope analysis. Gas chromatography coupled to isotope ratio mass spectrometry (GC/IRMS) has been well-established for compound-specific isotope analysis of volatile organic compounds within the last two decades. However, an interface combining liquid chromatography with isotope ratio mass spectrometry (LC/IRMS) was not commercially available until 2004. The current design of the interface requires using a carbon-free eluent in chromatographic separation. This requirement limits the application of the most frequently used reversed-phase liquid chromatography in CSIA, because the elution strength of water at room temperature is too low to serve as mobile phase in reversed-phase separations. In order to increase the elution strength of water, we propose using high temperature water for chromatographic elution. The polarity of water decreases with an increase of temperature, yielding increased elution strength in reversed-phase columns. Therefore, high temperature water can be used as eluent instead of organic solvent for combining reversed-phase liquid chromatography with isotope ratio mass spectrometry (RPLC/IRMS). Additionally, temperature gradients can replace organic solvent gradients to increase chromatographic resolution. This is very important for LC/IRMS analysis, as precise isotope analysis requires baseline separation of analytes. In this thesis, high-temperature reversed-phase liquid chromatography was coupled to, and for the first time carefully

Simultaneous determination of water-soluble vitamins in SRM 1849 Infant/Adult Nutritional Formula powder by liquid chromatography-isotope dilution mass spectrometry.

Science.gov (United States)

Goldschmidt, Robert J; Wolf, Wayne R

2010-05-01

Assessing dietary intake of vitamins from all sources, including foods, dietary supplements, and fortified foods, would be aided considerably by having analytical methodologies that are capable of simultaneous determination of several vitamins. Vitamins naturally present in foods may occur in different chemical forms, with levels ranging over several orders of magnitude. Vitamins in dietary supplements and fortified foods, however, are typically added in a single chemical form, and matrix issues are usually not as complex. These sources should thus be relatively amenable to approaches that aim for simultaneous determination of multiple vitamins. Our recent work has focused on development of liquid chromatography (LC)-UV/fluorescence and LC-tandem mass spectrometry methods for the simultaneous determination of water-soluble vitamins (thiamine, niacin, pyridoxine, pantothenic acid, folic acid, biotin, and riboflavin) in dietary supplement tablets and fortified foods, such as formula powders and breakfast cereals. As part of the validation of our methods and collaboration in characterization of a new NIST SRM 1849 Infant/Adult Nutritional Formula powder, we report data on SRM 1849 using isotope dilution mass spectrometric methods. Use of available NIST Standard Reference Materials(R) as test matrices in our method development and validation gives a benchmark for future application of these methods. We compare three chromatographic approaches and provide data on stability of vitamin standard solutions for LC-based multiple vitamin determinations.

Detection of triclocarban and two co-contaminating chlorocarbanilides in US aquatic environments using isotope dilution liquid chromatography tandem mass spectrometry.

Science.gov (United States)

Sapkota, Amir; Heidler, Jochen; Halden, Rolf U

2007-01-01

The antimicrobial compound triclocarban (TCC; 3,4,4'-trichlorocarbanilide; CAS# 101-20-2) is a high-production-volume chemical, recently suggested to cause widespread contamination of US water resources. To test this hypothesis, we developed an isotope dilution liquid chromatography electrospray ionization tandem mass spectrometry method for ultratrace analysis of TCC (0.9 ng/L detection limit) and analyzed low-volume water samples (200 mL) along with primary sludge samples from across the United States. All river water samples (100%) collected downstream of wastewater treatment plants had detectable levels of TCC, as compared to 56% of those taken upstream. Concentrations of TCC (mean+/-standard deviation) downstream of sewage treatment plants (84+/-110 ng/L) were significantly higher (P1219-99-4). In addition to TCC and DCC, municipal sludge contained a second co-contaminant, 3,3',4,4'-tetrachlorocarbanilide (TetraCC; CAS# 4300-43-0). Both newly detected compounds were present as impurities (0.2%(w/w) each) in technical grade TCC (99%). Application of the new method for chlorocarbanilide analysis yielded TCC occurrence data for 13 US states, confirmed the role of sewage treatment plants as environmental inputs of TCC, and identified DCC and TetraCC as previously unrecognized pollutants released into the environment alongside TCC.

Automated spike preparation system for Isotope Dilution Mass Spectrometry (IDMS)

International Nuclear Information System (INIS)

Maxwell, S.L. III; Clark, J.P.

1990-01-01

Isotope Dilution Mass Spectrometry (IDMS) is a method frequently employed to measure dissolved, irradiated nuclear materials. A known quantity of a unique isotope of the element to be measured (referred to as the ''spike'') is added to the solution containing the analyte. The resulting solution is chemically purified then analyzed by mass spectrometry. By measuring the magnitude of the response for each isotope and the response for the ''unique spike'' then relating this to the known quantity of the ''spike'', the quantity of the nuclear material can be determined. An automated spike preparation system was developed at the Savannah River Site (SRS) to dispense spikes for use in IDMS analytical methods. Prior to this development, technicians weighed each individual spike manually to achieve the accuracy required. This procedure was time-consuming and subjected the master stock solution to evaporation. The new system employs a high precision SMI Model 300 Unipump dispenser interfaced with an electronic balance and a portable Epson HX-20 notebook computer to automate spike preparation

Quantitation of DNA adducts by stable isotope dilution mass spectrometry

Science.gov (United States)

Tretyakova, Natalia; Goggin, Melissa; Janis, Gregory

2012-01-01

Exposure to endogenous and exogenous chemicals can lead to the formation of structurally modified DNA bases (DNA adducts). If not repaired, these nucleobase lesions can cause polymerase errors during DNA replication, leading to heritable mutations potentially contributing to the development of cancer. Due to their critical role in cancer initiation, DNA adducts represent mechanism-based biomarkers of carcinogen exposure, and their quantitation is particularly useful for cancer risk assessment. DNA adducts are also valuable in mechanistic studies linking tumorigenic effects of environmental and industrial carcinogens to specific electrophilic species generated from their metabolism. While multiple experimental methodologies have been developed for DNA adduct analysis in biological samples – including immunoassay, HPLC, and 32P-postlabeling – isotope dilution high performance liquid chromatography-electrospray ionization-tandem mass spectrometry (HPLC-ESI-MS/MS) generally has superior selectivity, sensitivity, accuracy, and reproducibility. As typical DNA adducts concentrations in biological samples are between 0.01 – 10 adducts per 108 normal nucleotides, ultrasensitive HPLC-ESI-MS/MS methodologies are required for their analysis. Recent developments in analytical separations and biological mass spectrometry – especially nanoflow HPLC, nanospray ionization MS, chip-MS, and high resolution MS – have pushed the limits of analytical HPLC-ESI-MS/MS methodologies for DNA adducts, allowing researchers to accurately measure their concentrations in biological samples from patients treated with DNA alkylating drugs and in populations exposed to carcinogens from urban air, drinking water, cooked food, alcohol, and cigarette smoke. PMID:22827593

Mixed-mode chromatography/isotope ratio mass spectrometry.

Science.gov (United States)

McCullagh, James S O

2010-03-15

Liquid chromatography coupled to molecular mass spectrometry (LC/MS) has been a standard technique since the early 1970s but liquid chromatography coupled to high-precision isotope ratio mass spectrometry (LC/IRMS) has only been available commercially since 2004. This development has, for the first time, enabled natural abundance and low enrichment delta(13)C measurements to be applied to individual analytes in aqueous mixtures creating new opportunities for IRMS applications, particularly for the isotopic study of biological molecules. A growing number of applications have been published in a range of areas including amino acid metabolism, carbohydrates studies, quantification of cellular and plasma metabolites, dietary tracer and nucleic acid studies. There is strong potential to extend these to new compounds and complex matrices but several challenges face the development of LC/IRMS methods. To achieve accurate isotopic measurements, HPLC separations must provide baseline-resolution between analyte peaks; however, the design of current liquid interfaces places severe restrictions on compatible flow rates and in particular mobile phase compositions. These create a significant challenge on which reports associated with LC/IRMS have not previously focused. Accordingly, this paper will address aspects of chromatography in the context of LC/IRMS, in particular focusing on mixed-mode separations and their benefits in light of these restrictions. It aims to provide an overview of mixed-mode stationary phases and of ways to improve high aqueous separations through manipulation of parameters such as column length, temperature and mobile phase pH. The results of several practical experiments are given using proteogenic amino acids and nucleosides both of which are of noted importance in the LC/IRMS literature. This communication aims to demonstrate that mixed-mode stationary phases provide a flexible approach given the constraints of LC/IRMS interface design and acts as a

Plutonium determination by isotope dilution

International Nuclear Information System (INIS)

Lucas, M.

1980-01-01

The principle is to add to a known amount of the analysed solution a known amount of a spike solution consisting of plutonium 242. The isotopic composition of the resulting mixture is then determined by surface ionization mass spectrometry, and the plutonium concentration in the solution is deduced, from this measurement. For irradiated fuels neutronic studies or for fissile materials balance measurements, requiring the knowledge of the ratio U/Pu or of concentration both uranium and plutonium, it is better to use the double spike isotope dilution method, with a spike solution of known 233 U- 242 Pu ratio. Using this method, the ratio of uranium to plutonium concentration in the irradiated fuel solution can be determined without any accurate measurement of the mixed amounts of sample and spike solutions. For fissile material balance measurements, the uranium concentration is determined by using single isotope dilution, and the plutonium concentration is deduced from the ratio Pu/U and U concentration. The main advantages of isotope dilution are its selectivity, accuracy and very high sensitivity. The recent improvements made to surface ionization mass spectrometers have considerably increased the precision of the measurements; a relative precision of about 0.2% to 0.3% is obtained currently, but it could be reduced to 0.1%, in the future, with a careful control of the experimental procedures. The detection limite is around 0.1 ppb [fr

Multi-element isotope dilution analyses using ICP-MS

International Nuclear Information System (INIS)

Volpe, A.M.

1996-01-01

Presently, 37 elements ranging from light (Li,B) through transition metals, noble, rare earth and heavy elements, to actinides and transuranics (Pu, Am, Cm) are measured by isotope dilution at Lawrence Livermore National Laboratory. Projects range from geological and hydrological to biological. The research goal is to measure accurately many elements present in diverse matrices at trace (ppb) levels using isotope dilution methods. Major advantages of isotope dilution methods are accuracy, elimination of ion intensity calibration, and quantitation for samples that require chemical separation. Accuracy depends on tracer isotope calibration, tracer-sample isotopic equilibration, and appropriate background, isobaric and mass bias corrections. Propagation of isotope ratio error due to improper tracer isotope addition is a major concern with multi-element analyses when abundances vary widely. 11 refs., 3 figs

Analysis of [U-13C6]glucose in human plasma using liquid chromatography/isotope ratio mass spectrometry compared with two other mass spectrometry techniques

NARCIS (Netherlands)

Schierbeek, H.; Moerdijk-Poortvliet, T.C.W.; van den Akker, C.H.P.; te Braake, F.W.J.; Boschker, H.T.S.; van Goudoever, J.B.

2009-01-01

The use of stable isotope labelled glucose provides insight into glucose metabolism. The 13C-isotopic enrichment of glucose is usually measured by gas chromatography/mass spectrometry (GC/MS) or gas chromatography/combustion/isotope ratio mass spectrometry (GC/C/IRMS). However, in both techniques

Approach for domestic preparation of standard material (LSD spike) for isotope dilution mass spectrometry

International Nuclear Information System (INIS)

Ishikawa, Fumitaka; Sumi, Mika; Chiba, Masahiko; Suzuki, Toru; Abe, Tomoyuki; Kuno, Yusuke

2008-01-01

The accountancy analysis of the nuclear fuel material at Plutonium Fuel Development Center of JAEA is performed by isotope dilution mass spectrometry (IDMS; Isotope Dilution Mass Spectrometry). IDMS requires the standard material called LSD spike (Large Size Dried spike) which is indispensable for the accountancy in the facilities where the nuclear fuel materials are handled. Although the LSD spike and Pu source material have been supplied from foreign countries, the transportation for such materials has been getting more difficult recently. This difficulty may affect the operation of nuclear facilities in the future. Therefore, research and development of the domestic LSD spike and base material has been performed at JAEA. Certification for such standard nuclear materials including spikes produced in Japan is being studied. This report presents the current status and the future plan for the technological development. (author)

Determination of six sulfonamide antibiotics, two metabolites and trimethoprim in wastewater by isotope dilution liquid chromatography/tandem mass spectrometry.

Science.gov (United States)

Le-Minh, Nhat; Stuetz, Richard M; Khan, Stuart J

2012-01-30

A highly sensitive method for the analysis of six sulfonamide antibiotics (sulfadiazine, sulfathiazole, sulfapyridine, sulfamerazine, sulfamethazine and sulfamethoxazole), two sulfonamide metabolites (N(4)-acetyl sulfamethazine and N(4)-acetyl sulfamethoxazole) and the commonly co-applied antibiotic trimethoprim was developed for the analysis of complex wastewater samples. The method involves solid phase extraction of filtered wastewater samples followed by liquid chromatography-tandem mass spectral detection. Method detection limits were shown to be matrix-dependent but ranged between 0.2 and 0.4 ng/mL for ultrapure water, 0.4 and 0.7 ng/mL for tap water, 1.4 and 5.9 ng/mL for a laboratory-scale membrane bioreactor (MBR) mixed liquor, 0.7 and 1.7 ng/mL for biologically treated effluent and 0.5 and 1.5 ng/g dry weight for MBR activated sludge. An investigation of analytical matrix effects was undertaken, demonstrating the significant and largely unpredictable nature of signal suppression observed for variably complex matrices compared to an ultrapure water matrix. The results demonstrate the importance of accounting for such matrix effects for accurate quantitation, as done in the presented method by isotope dilution. Comprehensive validation of calibration linearity, reproducibility, extraction recovery, limits of detection and quantification are also presented. Finally, wastewater samples from a variety of treatment stages in a full-scale wastewater treatment plant were analysed to illustrate the effectiveness of the method. Copyright © 2011 Elsevier B.V. All rights reserved.

Quantitation of Poly(ADP-Ribose) by Isotope Dilution Mass Spectrometry

DEFF Research Database (Denmark)

Zubel, Tabea; Martello, Rita; Bürkle, Alexander

2017-01-01

PARP inhibitors, which represent a novel class of promising chemotherapeutics. Previously, we have developed a bioanalytical platform based on isotope dilution mass spectrometry (LC-MS/MS) to quantify cellular PAR with unequivocal chemical specificity in absolute terms with femtomol sensitivity...... research, as well as in drug development (Martello et al. ACS Chem Biol 8(7):1567-1575, 2013; Mangerich et al. Toxicol Lett 244:56-71, 2016). Here, we present an improved and adjusted version of the original protocol by Martello/Mangerich et al., which uses UPLC-MS/MS instrumentation....

Simultaneous analysis of urinary phthalate metabolites of residents in Korea using isotope dilution gas chromatography-mass spectrometry.

Science.gov (United States)

Kim, Miok; Song, Na Rae; Choi, Jong-Ho; Lee, Jeongae; Pyo, Heesoo

2014-02-01

Phthalates are used in industry products, household items, and medical tools as plasticizers. Human exposure to phthalates has raised concern about its toxicity. In the present study, optimization was conducted for the simultaneous analysis of eight kinds of phthalate metabolites using gas chromatography-mass spectrometry (GC-MS): MEP, MiBP, MnBP, MBzP, MiNP, MEHP, MEOHP, and MEHHP. In order to minimize the matrix effect and to do quantitative analysis, isotope dilution and LLE-GC-MS methods were performed. Urine samples were enzymatically hydrolyzed, extracted with a mixture of n-hexane and ethyl ether (8:2; v:v), and subsequently derivatized with trimethylsilylation. All eight kinds of analytes showed clear resolution and high reproducibility in GC-MS results. The method detection limit ranged from 0.05 ng/mL to 0.2 ng/mL. Calibration curves were found to be linear from 0.2 to 100 ng/mL with -(2)>0.992. The relative standard deviation of the intraday precision using water and urine ranged from 2.1% to 16.3%. The analysis was performed with urine samples that were collected from adults residing in the Republic of Korea. The analyzed concentration results were compared according to gender and region. As a result, DEHP metabolites showed the highest detected concentration (75.92 μg/g creatinine, 100%), and MiNP, a metabolite of DiNP, showed the lowest detected concentration (0.42 μg/g creatinine, 22.5%). On average, female urine (200.76 μg/g creatinine) had a higher detected concentration of ∑8 phthalate metabolites than male urine. Samples from rural regions (211.96 μg/g creatinine) had higher levels than samples from urban regions. © 2013.

Application of the mass spectrometry-isotope dilution technique for the determination of uranium contents in rocks

International Nuclear Information System (INIS)

Kakazu, M.H.; Iyer, S.S.

1980-01-01

Application of the spectrometric isotope dilution technique for the accurate determination of parts per million range of uranium in rock samples is described. The various aspects of the method like sample dissolution, ion exchange separation, mass spectrometric procedures are discussed. A single filament ionization source was employed for the isotope analysis. A carbon reduction method was used to reduce uranium oxide ions to uranium metal ions. The tracer solution for isotope dilution was prepared from National Bureau of Standards uranium isotopic Standard NBS U-970. Uranium contents are meassured for nine rock samples and the values obtained are compared with the uranium values measured by others workers. Errors caused in the uranium determination due to sample splitting problems as well as the incomplete acid digestion of the samples are discussed. (Author) [pt

Stable carbon isotopic composition of gasolines determined by isotope ratio monitoring gas chromatography mass spectrometry

Energy Technology Data Exchange (ETDEWEB)

Smallwood, B.J.; Philp, R.P.; Allen, J.D. [University of Oklahoma, Norman, OK (United States). School of Geology and Geophysics

2002-07-01

A large number of underground gasoline storage facilities in the United States continuously leak gasoline into the subsurface, which makes gasoline a major groundwater contaminant. Gas chromatography (GC) and gas chromatography-mass spectrometry (GC-MS) are used currently to characterize contaminated groundwater and soils. Correlations of contaminants with suspected source(s) are extremely difficult by these techniques because many gasolines have similar hydrocarbon distributions. The present study applied the technique of isotope ratio monitoring gas chromatography-mass spectrometry (irmGC-MS) to 19 gasoline samples from different areas of the USA. This allows a much better correlation of gasoline contaminants to source. Data obtained indicate a wide range of {sup {delta}}{sup 13}C values for 16 ubiquitous compounds in the gasolines. The majority of samples could be distinguished from each other on the basis of {sup {delta}}{sup 13}C hydrocarbon composition. The oxygenated additive methyl tertiary butyl ether (MTBE) was present in ten of the gasolines analyzed, and had a relatively narrow range of {sup {delta}}{sup 13}C values (-30.4 to -28.3 per mille). Preliminary investigations were also made to determine the extent of carbon isotopic fractionation after simple water washing and evaporation experiments. Results indicate that the majority of compounds did not undergo significant carbon isotopic fractionation as a result of these processes. (author)

[Uncertainty evaluation of the determination of toxic equivalent quantity of polychlorinated dibenzo-p-dioxins and dibenzofurans in soil by isotope dilution high resolution gas chromatography and high resolution mass spectrometry].

Science.gov (United States)

Du, Bing; Liu Aimin; Huang, Yeru

2014-09-01

Polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) in soil samples were analyzed by isotope dilution method with high resolution gas chromatography and high resolution mass spectrometry (ID-HRGC/HRMS), and the toxic equivalent quantity (TEQ) were calculated. The impacts of major source of measurement uncertainty are discussed, and the combined relative standard uncertainties were calculated for each 2, 3, 7, 8 substituted con- gener. Furthermore, the concentration, combined uncertainty and expanded uncertainty for TEQ of PCDD/Fs in a soil sample in I-TEF, WHO-1998-TEF and WHO-2005-TEF schemes are provided as an example. I-TEF, WHO-1998-TEF and WHO-2005-TEF are the evaluation schemes of toxic equivalent factor (TEF), and are all currently used to describe 2,3,7,8 sub- stituted relative potencies.

Direct determination of fatty acid esters of 3-chloro-1, 2-propanediol in edible vegetable oils by isotope dilution - ultra high performance liquid chromatography - triple quadrupole mass spectrometry.

Science.gov (United States)

Li, Heli; Chen, Dawei; Miao, Hong; Zhao, Yunfeng; Shen, Jianzhong; Wu, Yongning

2015-09-04

A selective and sensitive ultra-high performance liquid chromatography - triple quadrupole mass spectrometry (UHPLC-MS/MS) method coupled with matrix solid phase dispersion (MSPD) extraction was developed for the direct determination of fatty acid esters of 3-chloro-1,2-propanediol (3-MCPD esters) in edible vegetable oils. The method integrated the isotope dilution technique, MSPD extraction and UHPLC - MS/MS analysis with multi-reaction monitoring mode (MRM). Matrix-matched calibration curves showed good linearity within the range of 0.01-10mgL(-1) with the correlation coefficient not less than 0.999. Limits of detection (LODs) and limit of quantification (LOQs) of the 3-MCPD esters fell into the range of 0.0001-0.02mgkg(-1) and 0.0004-0.05mgkg(-1), respectively. The recoveries for the spiked extra virgin olive oils ranged from 94.4% to 108.3%, with the relative standard deviations (RSD) ranging from 0.6% to 10.5%. The method was applied for the oil sample (T2642) of the official Food Analysis Performance Assessment Scheme (FAPAS) in 2014 and other real samples from supermarket, and the results showed that the present method was comparative to the gas chromatography-mass spectrometry (GC-MS) method based on the improved German Society for Fat Science (DGF) standard method C-III 18 (09) except for palm oil. Copyright © 2015. Published by Elsevier B.V.

Quantification of 13 priority polycyclic aromatic hydrocarbons in human urine by headspace solid-phase microextraction gas chromatography-isotope dilution mass spectrometry

Energy Technology Data Exchange (ETDEWEB)

Campo, Laura [Department of Occupational and Environmental Health, University of Milan and Fondazione IRCCS Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena, Milan (Italy)], E-mail: laura.campo@unimi.it; Mercadante, Rosa; Rossella, Federica; Fustinoni, Silvia [Department of Occupational and Environmental Health, University of Milan and Fondazione IRCCS Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena, Milan (Italy)

2009-01-12

Polycyclic aromatic hydrocarbons (PAHs) are common environmental pollutants in both living and working environments. The aim of this study was the development of a headspace solid-phase microextraction gas chromatography-isotope dilution mass spectrometry (HS-SPME/GC-IDMS) method for the simultaneous quantification of 13 PAHs in urine samples. Different parameters affecting PAHs extraction by HS-SPME were considered and optimized: type/thickness of fiber coatings, extraction temperature/time, desorption temperature/time, ionic strength and sample agitation. The stability of spiked PAHs solutions and of real urine samples stored up to 90 days in containers of different materials was evaluated. In the optimized method, analytes were absorbed for 60 min at 80 deg. C in the sample headspace with a 100 {mu}m polydimethylsiloxane fiber. The method is very specific, with linear range from the limit of quantification to 8.67 x 10{sup 3} ng L{sup -1}, a within-run precision of <20% and a between-run precision of <20% for 2-, 3- and 4-ring compounds and of <30% for 5-ring compounds, trueness within 20% of the spiked concentration, and limit of quantification in the 2.28-2.28 x 10{sup 1} ng L{sup -1} range. An application of the proposed method using 15 urine samples from subjects exposed to PAHs at different environmental levels is shown.

Liquid chromatography with isotope-dilution mass spectrometry for determination of water-soluble vitamins in foods.

Science.gov (United States)

Phillips, Melissa M

2015-04-01

Vitamins are essential for improving and maintaining human health, and the main source of vitamins is the diet. Measurement of the quantities of water-soluble vitamins in common food materials is important to understand the impact of vitamin intake on human health, and also to provide necessary information for regulators to determine adequate intakes. Liquid chromatography (LC) and mass spectrometry (MS) based methods for water-soluble vitamin analysis are abundant in the literature, but most focus on only fortified foods or dietary supplements or allow determination of only a single vitamin. In this work, a method based on LC/MS and LC/MS/MS has been developed to allow simultaneous quantitation of eight water-soluble vitamins, including multiple forms of vitamins B3 and B6, in a variety of fortified and unfortified food-matrix Standard Reference Materials (SRMs). Optimization of extraction of unbound vitamin forms and confirmation using data from external laboratories ensured accuracy in the assigned values, and addition of stable isotope labeled internal standards for each of the vitamins allowed for increased precision.

Determination of total uranium by mass spectrometry utilizing the isotopic dilution technique

International Nuclear Information System (INIS)

Cretella, R.F.; Noutary, C.J.; Servant, R.E.

1981-01-01

The isotopic dilution associated to mass spectrometry is a high-sensitivity technique that allows to work with microquantities of the sample, making it possible to analize the content in highly radioactive solutions with excellent accuracy and minimum risk. The proposed technique is described and its results are discussed through the analysis of: 1) A synthetic sample that simulates dissolved spent fuel elements; 2) Uranium dioxide of nuclear purity and 3) Uranium concentrate. 233 U(ORNL) was employed as a tracer and a Nuclide 12-90-SU mass spectrometer of simple magnetic focus as measurement instrument. The accuracy reached in the analyses is better than 0.5% with a reliability of 95%. The analysis of the errors shows that their main contributing source are the errors in the measurement of the isotopic ratios. (M.E.L.) [es

Collaborative trial validation study of two methods, one based on high performance liquid chromatography-tandem mass spectrometry and on gas chromatography-mass spectrometry for the determination of acrylamide in bakery and potato products.

Science.gov (United States)

Wenzl, Thomas; Karasek, Lubomir; Rosen, Johan; Hellenaes, Karl-Erik; Crews, Colin; Castle, Laurence; Anklam, Elke

2006-11-03

A European inter-laboratory study was conducted to validate two analytical procedures for the determination of acrylamide in bakery ware (crispbreads, biscuits) and potato products (chips), within a concentration range from about 20 microg/kg to about 9000 microgg/kg. The methods are based on gas chromatography-mass spectrometry (GC-MS) of the derivatised analyte and on high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) of native acrylamide. Isotope dilution with isotopically labelled acrylamide was an integral part of both methods. The study was evaluated according to internationally accepted guidelines. The performance of the HPLC-MS/MS method was found to be superior to that of the GC-MS method and to be fit-for-the-purpose.

Simultaneous stable carbon isotopic analysis of wine glycerol and ethanol by liquid chromatography coupled to isotope ratio mass spectrometry.

Science.gov (United States)

Cabañero, Ana I; Recio, Jose L; Rupérez, Mercedes

2010-01-27

A novel procedure was established for the simultaneous characterization of wine glycerol and ethanol (13)C/(12)C isotope ratio, using liquid chromatography/isotope ratio mass spectrometry (LC-IRMS). Several parameters influencing separation of glycerol and ethanol from wine matrix were optimized. Results obtained for 35 Spanish samples exposed no significant differences and very strong correlations (r = 0.99) between the glycerol (13)C/(12)C ratios obtained by an alternative method (gas chromatography/isotope ratio mass spectrometry) and the proposed new methodology, and between the ethanol (13)C/(12)C ratios obtained by the official method (elemental analyzer/isotope ratio mass spectrometry) and the proposed new methodology. The accuracy of the proposed method varied from 0.01 to 0.19 per thousand, and the analytical precision was better than 0.25 per thousand. The new developed LC-IRMS method it is the first isotopic method that allows (13)C/(12)C determination of both analytes in the same run directly from a liquid sample with no previous glycerol or ethanol isolation, overcoming technical difficulties associated with complex sample treatment and improving in terms of simplicity and speed.

Online Stable Isotope Analysis of Dissolved Organic Carbon Size Classes Using Size Exclusion Chromatography Coupled to an Isotope Ratio Mass Spectrometer

Digital Repository Service at National Institute of Oceanography (India)

Malik, A.; Scheibe, A.; LokaBharathi, P.A.; Gleixner, G.

size classes by coupling high-performance liquid chromatography (HPLC) - size exclusion chromatography (SEC) to online isotope ratio mass spectrometry (IRMS). This represents a significant methodological contribution to DOC research. The interface...

Differentiation of endogenous and exogenous steroids by gas chromatography-combustion-mass spectrometry isotope ratio

International Nuclear Information System (INIS)

Montes de Oca Porto, Rodny; Rosado Perez, Aristides; Correa Vidal, Margarita Teresa

2007-01-01

Urinary steroids profiles are used to control the misuse of endogenous steroids such as testosterone and dihydrotestosterone. The testosterone/epistestosterone ratio, measured by Gas Chromatography-Mass Spectrometry, is used to control testosterone administration. When T/E ratio is higher than 4, consumption of testosterone or its precursors is suspected. Recent researches have demonstrated the effectiveness of Carbon Isotope Ratio Mass Spectrometry to detect and confirm endogenous steroids administration. The ratio of the two stable carbon isotopes 1 3 C and 1 2 C allows the differentiation of natural and synthetic steroids because synthetic steroids have lower 1 3 C abundance. In fact, the carbon isotope ratios can be used to determine endogenous steroids administration even when testosterone/epistestosterone ratio is at its normal value. In the current work, some of the most important aspects related to differentiation of endogenous and exogenous steroids by means of Gas Chromatography-Combustion-Isotope Ratio Mass Spectrometry are discussed. Also, this article provides a review about the purification and sample preparation previous to the analysis, and diet effects on carbon isotope ratio of endogenous anabolics steroids is presented too

Review: Current applications and challenges for liquid chromatography coupled to isotope ratio mass spectrometry (LC/IRMS).

Science.gov (United States)

Godin, Jean-Philippe; McCullagh, James S O

2011-10-30

High-precision isotope analysis is recognized as an essential research tool in many fields of study. Until recently, continuous flow isotope ratio mass spectrometry (CF-IRMS) was available via an elemental analyzer or a gas chromatography inlet system for compound-specific analysis of light stable isotopes. In 2004, however, an interface that coupled liquid chromatography with IRMS (LC/IRMS) became commercially available for the first time. This brought the capability for new areas of application, in particular enabling compound-specific δ(13)C analysis of non-volatile, aqueous soluble, compounds from complex mixtures. The interface design brought with it several analytical constraints, however, in particular a lack of compatibility with certain types of chromatography as well as limited flow rates and mobile phase compositions. Routine LC/IRMS methods have, however, been established for measuring the δ(13)C isotopic ratios of underivatized individual compounds for application in archeology, nutrition and physiology, geochemistry, hydrology, soil science and food authenticity. Seven years after its introduction, we review the technical advances and constraints, methodological developments and new applications of liquid chromatography coupled to isotope ratio mass spectrometry. Copyright © 2011 John Wiley & Sons, Ltd.

Isotope dilution liquid chromatography - mass spectrometry methods for fat- and water-soluble vitamins in nutritional formulations.

Science.gov (United States)

Phinney, Karen W; Rimmer, Catherine A; Thomas, Jeanice Brown; Sander, Lane C; Sharpless, Katherine E; Wise, Stephen A

2011-01-01

Vitamins are essential to human health, and dietary supplements containing vitamins are widely used by individuals hoping to ensure they have adequate intake of these important nutrients. Measurement of vitamins in nutritional formulations is necessary to monitor regulatory compliance and in studies examining the nutrient intake of specific populations. Liquid chromatographic methods, primarily with UV absorbance detection, are well established for both fat- and water-soluble measurements, but they do have limitations for certain analytes and may suffer from a lack of specificity in complex matrices. Liquid chromatography-mass spectrometry (LC-MS) provides both sensitivity and specificity for the determination of vitamins in these matrices, and simultaneous analysis of multiple vitamins in a single analysis is often possible. In this work, LC-MS methods were developed for both fat- and water-soluble vitamins and applied to the measurement of these analytes in two NIST Standard Reference Materials. When possible, stable isotope labeled internal standards were employed for quantification.

Quantification of abscisic acid in grapevine leaf (Vitis vinifera) by isotope-dilution liquid chromatography-mass spectrometry.

Science.gov (United States)

Vilaró, Francisca; Canela-Xandri, Anna; Canela, Ramon

2006-09-01

A specific, sensitive, precise, and accurate method for the determination of abscisic acid (ABA) in grapevine leaf tissues is described. The method employs high-performance liquid chromatography and electrospray ionization-mass spectrometry (LC-ESI-MS) in selected ion monitoring mode (SIM) to analyze ABA using a stable isotope-labeled ABA as an internal standard. Absolute recoveries ranged from 72% to 79% using methanol/water pH 5.5 (50:50 v/v) as an extraction solvent. The best efficiency was obtained when the chromatographic separation was carried out by using a porous graphitic carbon (PGC) column. The statistical evaluation of the method was satisfactory in the work range. A relative standard deviation (RDS) of < 5.5% and < 6.0% was obtained for intra-batch and inter-batch comparisons, respectively. As for accuracy, the relative error (%Er) was between -2.7 and 4.3%, and the relative recovery ranged from 95% to 107%.

Field ionization mass spectrometry (FIMS) applied to tracer studies and isotope dilution analysis

International Nuclear Information System (INIS)

Anbar, M.; Heck, H.d'A.; McReynolds, J.H.; St John, G.A.

1975-01-01

The nonfragmenting nature of field ionization mass spectrometry makes it a preferred technique for the isotopic analysis of multilabeled organic compounds. The possibility of field ionization of nonvolatile thermolabile materials significantly extends the potential uses of this technique beyond those of conventional ionization methods. Multilabeled tracers may be studied in biological systems with a sensitivity comparable to that of radioactive tracers. Isotope dilution analysis may be performed reliably by this technique down to picogram levels. These techniques will be illustrated by a number of current studies using multilabeled metabolites and drugs. The scope and limitations of the methodology are discussed

Stable isotope dilution analysis by thermal ionization mass spectrometry. Pt. 2

International Nuclear Information System (INIS)

Broekman, A.; Raaphorst, J.G. van

1984-01-01

The combination of stable isotope dilution analysis (SIDA) and thermal ionization mass spectrometry (TIMS) is in use for lead and uranium determination at milligram per kilogram levels for over 20 years. However, several other elements can also be determined accurately by SIDA/TIMS. In this study the determinations of cadmium and copper are described. Details of the digestion, electrochemical and ion-exchange separations and the loading of the elements on a filament are given. The advantages of the SIDA/TIMS technique are shown and illustrated with results for several certified reference materials. (orig.) [de

Precise determination of sodium in serum by simulated isotope dilution method of inductively coupled plasma mass spectrometry

International Nuclear Information System (INIS)

Yan Ying; Zhang Chuanbao; Zhao Haijian; Chen Wenxiang; Shen Ziyu; Wang Xiaoru; Chen Dengyun

2007-01-01

A new precise and accurate method for the determination of sodium in serum by inductively coupled plasma mass spectrometry (ICP-MS) was developed. Since 23 Na is the single isotope element, 27 Al is selected as simulated isotope of Na. Al is spiked into serum samples and Na standard solution. 23 Na/ 27 Al ratio in the Na standard solution is determined to assume the natural Na isotope ratio. The serums samples are digested by purified HNO 3 /H 2 O 2 and diluted to get about 0.6 μg·g -1 Al solutions, and the 23 Na/ 27 Al ratios of the serum samples are obtained to calculate the accurate Na concentrations basing on the isotope dilution method. When the simulated isotope dilution method of ICP-MS is applied and Al is selected as the simulated isotope of Na, the precise and accurate Na concentrations in the serums are determined. The inter-day precision of CV<0.13% for one same serum sample is obtained during 3 days 4 measurements. The spike recoveries are between 99.69% and 100.60% for 4 different serum samples and 3 days multi-measurements. The results of measuring standard reference materials of serum sodium are agree with the certified value. The relative difference between 3 days is 0.22%-0.65%, and the relative difference in one bottle is 0.15%-0.44%. The ICP-MS and Al simulated isotope dilution method is proved to be not only precise and accurate, but also quick and convenient for measuring Na in serum. It is promising to be a reference method for precise determination of Na in serum. Since Al is a low cost isotope dilution reagent, the method is possible to be widely applied for serum Na determination. (authors)

Evaluation of bilirubin interference and accuracy of six creatinine assays compared with isotope dilution-liquid chromatography mass spectrometry.

Science.gov (United States)

Nah, Hyunjin; Lee, Sang-Guk; Lee, Kyeong-Seob; Won, Jae-Hee; Kim, Hyun Ok; Kim, Jeong-Ho

2016-02-01

The aim of this study was to estimate bilirubin interference and accuracy of six routine methods for measuring creatinine compared with isotope dilution-liquid chromatography mass spectrometry (ID-LC/MS). A total of 40 clinical serum samples from 31 patients with serum total bilirubin concentration >68.4μmol/L were collected. Serum creatinine was measured using two enzymatic reagents and four Jaffe reagents as well as ID-LC/MS. Correlations between bilirubin concentration and percent difference in creatinine compared with ID-LC/MS were analyzed to investigate bilirubin interference. Bias estimations between the six reagents and ID-LC/MS were performed. Recovery tests using National Institute of Standards and Technology (NIST) Standard Reference Material (SRM) 967a were also performed. Both the enzymatic methods showed no bilirubin interference. However, three of the four Jaffe methods demonstrated significant bilirubin concentration-dependent interference in samples with creatinine levels creatinine levels ranging from 53.0 to 97.2μmol/L. Comparison of these methods with ID-LC/MS using patients' samples with elevated bilirubin revealed that the tested methods failed to achieve the bias goal at especially low levels of creatinine. In addition, recovery test using NIST SRM 967a showed that bias in one Jaffe method and two enzymatic methods did not achieve the bias goal at either low or high level of creatinine, indicating they had calibration bias. One enzymatic method failed to achieve all the bias goals in both comparison experiment and recovery test. It is important to understand that both bilirubin interference and calibration traceability to ID-LC/MS should be considered to improve the accuracy of creatinine measurement. Copyright © 2015 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

An isotope dilution ultra high performance liquid chromatography-tandem mass spectrometry method for the simultaneous determination of sugars and humectants in tobacco products.

Science.gov (United States)

Wang, Liqun; Cardenas, Roberto Bravo; Watson, Clifford

2017-09-08

CDC's Division of Laboratory Sciences developed and validated a new method for the simultaneous detection and measurement of 11 sugars, alditols and humectants in tobacco products. The method uses isotope dilution ultra high performance liquid chromatography coupled with tandem mass spectrometry (UHPLC-MS/MS) and has demonstrated high sensitivity, selectivity, throughput and accuracy, with recoveries ranging from 90% to 113%, limits of detection ranging from 0.0002 to 0.0045μg/mL and coefficients of variation (CV%) ranging from 1.4 to 14%. Calibration curves for all analytes were linear with linearity R 2 values greater than 0.995. Quantification of tobacco components is necessary to characterize tobacco product components and their potential effects on consumer appeal, smoke chemistry and toxicology, and to potentially help distinguish tobacco product categories. The researchers analyzed a variety of tobacco products (e.g., cigarettes, little cigars, cigarillos) using the new method and documented differences in the abundance of selected analytes among product categories. Specifically, differences were detected in levels of selected sugars found in little cigars and cigarettes, which could help address appeal potential and have utility when product category is unknown, unclear, or miscategorized. Copyright © 2017. Published by Elsevier B.V.

Evaluation of the combined measurement uncertainty in isotope dilution by MC-ICP-MS

International Nuclear Information System (INIS)

Fortunato, G.; Wunderli, S.

2003-01-01

The combination of metrological weighing, the measurement of isotope amount ratios by a multicollector inductively coupled plasma mass spectrometer (MC-ICP-MS) and the use of high-purity reference materials are the cornerstones to achieve improved results for the amount content of lead in wine by the reversed isotope dilution technique. Isotope dilution mass spectrometry (IDMS) and reversed IDMS have the potential to be a so-called primary method, with which close comparability and well-stated combined measurement uncertainties can be obtained. This work describes the detailed uncertainty budget determination using the ISO-GUM approach. The traces of lead in wine were separated from the matrix by ion exchange chromatography after HNO 3 /H 2 O 2 microwave digestion. The thallium isotope amount ratio (n( 205 Tl)/n( 203 Tl)) was used to correct for mass discrimination using an exponential model approach. The corrected lead isotope amount ratio n( 206 Pb)/n( 208 Pb) for the isotopic standard SRM 981 measured in our laboratory was compared with ratio values considered to be the least uncertain. The result has been compared in a so-called pilot study ''lead in wine'' organised by the CCQM (Comite Consultatif pour la Quantite de Matiere, BIPM, Paris; the highest measurement authority for analytical chemical measurements). The result for the lead amount content k(Pb) and the corresponding expanded uncertainty U given by our laboratory was:k(Pb)=1.329 x 10-10mol g-1 (amount content of lead in wine)U[k(Pb)]=1.0 x 10-12mol g-1 (expanded uncertainty U=k x uc, k=2) The uncertainty of the main influence parameter of the combined measurement uncertainty was determined to be the isotope amount ratio R 206,B of the blend between the enriched spike and the sample. (orig.)

The analysis of uranium in environmental sample by mass spectrometer combined with isotopic dilution

International Nuclear Information System (INIS)

Fu Zhonghua; Jia Baoting; Han Jun

2003-01-01

Uranium in the environmental sample was analyzed by mass spectrometer combined with isotopic dilution. Before mass spectrometer analysis, samples were dissolved in a concentrated acidic solution containing HNO 3 , HF and HClO 4 and chemically processed to suit the analysis requirement. Analysis results indicated that the uranium content was 0.08 μg/g in river water, 0.1 μg/g in evergreen foliage, and 5-11 μg/g in surface soil respectively. (authors)

Isotope ratio mass spectrometry coupled to liquid and gas chromatography for wine ethanol characterization.

Science.gov (United States)

Cabañero, Ana I; Recio, Jose L; Rupérez, Mercedes

2008-10-01

Two new procedures for wine ethanol 13C/12C isotope ratio determination, using high-performance liquid chromatography and gas chromatography isotope ratio mass spectrometry (HPLC/IRMS and GC/IRMS), have been developed to improve isotopic methods dedicated to the study of wine authenticity. Parameters influencing separation of ethanol from wine matrix such as column, temperature, mobile phase, flow rates and injection mode were investigated. Twenty-three wine samples from various origins were analyzed for validation of the procedures. The analytical precision was better than 0.15 per thousand, and no significant isotopic fractionation was observed employing both separative techniques coupled to IRMS. No significant differences and a very strong correlation (r = 0.99) were observed between the 13C/12C ratios obtained by the official method (elemental analyzer/isotope ratio mass spectrometry) and the proposed new methodology. The potential advantages of the developed methods over the traditional one are speed (reducing time required from hours to minutes) and simplicity. In addition, these are the first isotopic methods that allow 13C/12C determination directly from a liquid sample with no previous ethanol isolation, overcoming technical difficulties associated with sample treatment.

Accurate determination of selected pesticides in soya beans by liquid chromatography coupled to isotope dilution mass spectrometry.

Science.gov (United States)

Huertas Pérez, J F; Sejerøe-Olsen, B; Fernández Alba, A R; Schimmel, H; Dabrio, M

2015-05-01

A sensitive, accurate and simple liquid chromatography coupled with mass spectrometry method for the determination of 10 selected pesticides in soya beans has been developed and validated. The method is intended for use during the characterization of selected pesticides in a reference material. In this process, high accuracy and appropriate uncertainty levels associated to the analytical measurements are of utmost importance. The analytical procedure is based on sample extraction by the use of a modified QuEChERS (quick, easy, cheap, effective, rugged, safe) extraction and subsequent clean-up of the extract with C18, PSA and Florisil. Analytes were separated on a C18 column using gradient elution with water-methanol/2.5 mM ammonium acetate mobile phase, and finally identified and quantified by triple quadrupole mass spectrometry in the multiple reaction monitoring mode (MRM). Reliable and accurate quantification of the analytes was achieved by means of stable isotope-labelled analogues employed as internal standards (IS) and calibration with pure substance solutions containing both, the isotopically labelled and native compounds. Exceptions were made for thiodicarb and malaoxon where the isotopically labelled congeners were not commercially available at the time of analysis. For the quantification of those compounds methomyl-(13)C2(15)N and malathion-D10 were used respectively. The method was validated according to the general principles covered by DG SANCO guidelines. However, validation criteria were set more stringently. Mean recoveries were in the range of 86-103% with RSDs lower than 8.1%. Repeatability and intermediate precision were in the range of 3.9-7.6% and 1.9-8.7% respectively. LODs were theoretically estimated and experimentally confirmed to be in the range 0.001-0.005 mg kg(-1) in the matrix, while LOQs established as the lowest spiking mass fractionation level were in the range 0.01-0.05 mg kg(-1). The method reliably identifies and quantifies the

Quantification of 2-acetyl-1-pyrroline in rice by stable isotope dilution assay through headspace solid-phase microextraction coupled to gas chromatography-tandem mass spectrometry

Energy Technology Data Exchange (ETDEWEB)

Maraval, Isabelle [UMR Qualisud, CIRAD, 73 Rue J. F. Breton, 34398 Montpellier Cedex 5 (France); UMR Qualisud, Universite Montpellier 2, place E. Bataillon, 34095 Montpellier Cedex 5 (France); Sen, Kemal [Department of Food Engineering, Faculty of Agriculture, University of Cukurova, 01330 Adana (Turkey); Agrebi, Abdelhamid; Menut, Chantal; Morere, Alain [UMR 5247, Institut des Biomolecules Max Mousseron (IBMM), CNRS, Universites Montpellier 2 et 1, Ecole Nationale Superieure de Chimie de Montpellier, 8 Rue de l' Ecole Normale, 34296 Montpellier Cedex 5 (France); Boulanger, Renaud [UMR Qualisud, CIRAD, 73 Rue J. F. Breton, 34398 Montpellier Cedex 5 (France); Gay, Frederic [CIRAD, DORAS Centre, Research and Development Building, Kasetsart University, Bangkok 10900 (Thailand); Mestres, Christian [UMR Qualisud, CIRAD, 73 Rue J. F. Breton, 34398 Montpellier Cedex 5 (France); Gunata, Ziya, E-mail: zgunata@univ-montp2.fr [UMR Qualisud, Universite Montpellier 2, place E. Bataillon, 34095 Montpellier Cedex 5 (France)

2010-08-24

A new and convenient synthesis of 2-acetyl-1-pyrroline (2AP), a potent flavor compound in rice, and its ring-deuterated analog, 2-acetyl-1-d{sub 2}-pyrroline (2AP-d{sub 2}), was reported. A stable isotope dilution assay (SIDA), involving headspace solid-phase microextraction (HS-SPME) combined with gas chromatography-positive chemical ionization-ion trap-tandem mass spectrometry (GC-PCI-IT-MS-MS), was developed for 2AP quantification. A divinylbenzene/carboxen/polydimethylsiloxane (DVB/CAR/PDMS) fiber was used for HS-SPME procedure and parameters affecting analytes recovery, such as extraction time and temperature, pH and salt, were studied. The repeatability of the method (n = 10) expressed as relative standard deviation (RSD) was 11.6%. A good linearity was observed from 5.9 to 779 ng of 2AP (r{sup 2} = 0.9989). Limits of detection (LOD) and quantification (LOQ) for 2AP were 0.1 and 0.4 ng g{sup -1} of rice, respectively. The recovery of spiked 2AP from rice matrix was almost complete. The developed method was applied to the quantification of 2AP in aerial parts and grains of scented and non-scented rice cultivars.

Odorant Screening and Quantitation of Thiols in Carmenere Red Wine by Gas Chromatography-Olfactometry and Stable Isotope Dilution Assays.

Science.gov (United States)

Pavez, Carolina; Agosin, Eduardo; Steinhaus, Martin

2016-05-04

The sensory impact of thiols in Vitis vinifera 'Carmenere' red wines was evaluated. For this purpose, aroma extract dilution analysis was applied to the thiols isolated from a Carmenere red wine by affinity chromatography with a mercurated agarose gel. Results revealed the presence of four odorants, identified as 2-furanylmethanethiol, 3-sulfanylhexyl acetate, 3-sulfanyl-1-hexanol, and 2-methyl-3-sulfanyl-1-butanol, with the latter being described here for the first time in Carmenere red wines. Quantitation of the four thiols in the Carmenere wine screened by aroma extract dilution analysis and in three additional Carmenere wines by stable isotope dilution assays resulted in concentrations above the respective orthonasal odor detection threshold values. Triangle tests applied to wine model solutions with and without the addition of the four thiols showed significant differences, thus suggesting that the compounds do have the potential to influence the overall aroma of red wine.

Characterizing uranium oxide reference particles for isotopic abundances and uranium mass by single particle isotope dilution mass spectrometry

International Nuclear Information System (INIS)

Kraiem, M.; Richter, S.; Erdmann, N.; Kühn, H.; Hedberg, M.; Aregbe, Y.

2012-01-01

Highlights: ► A method to quantify the U mass in single micron particles by ID-TIMS was developed. ► Well-characterized monodisperse U-oxide particles produced by an aerosol generator were used. ► A linear correlation between the mass of U and the volume of particle(s) was found. ► The method developed is suitable for determining the amount of U in a particulate reference material. - Abstract: Uranium and plutonium particulate test materials are becoming increasingly important as the reliability of measurement results has to be demonstrated to regulatory bodies responsible for maintaining effective nuclear safeguards. In order to address this issue, the Institute for Reference Materials and Measurements (IRMM) in collaboration with the Institute for Transuranium Elements (ITU) has initiated a study to investigate the feasibility of preparing and characterizing a uranium particle reference material for nuclear safeguards, which is finally certified for isotopic abundances and for the uranium mass per particle. Such control particles are specifically required to evaluate responses of instruments based on mass spectrometric detection (e.g. SIMS, TIMS, LA-ICPMS) and to help ensuring the reliability and comparability of measurement results worldwide. In this paper, a methodology is described which allows quantifying the uranium mass in single micron particles by isotope dilution thermal ionization mass spectrometry (ID-TIMS). This methodology is characterized by substantial improvements recently achieved at IRMM in terms of sensitivity and measurement accuracy in the field of uranium particle analysis by TIMS. The use of monodisperse uranium oxide particles prepared using an aerosol generation technique developed at ITU, which is capable of producing particles of well-characterized size and isotopic composition was exploited. The evidence of a straightforward correlation between the particle volume and the mass of uranium was demonstrated in this study

Direct quantification of creatinine in human urine by using isotope dilution extractive electrospray ionization tandem mass spectrometry

International Nuclear Information System (INIS)

Li Xue; Fang Xiaowei; Yu Zhiqiang; Sheng Guoying; Wu Minghong; Fu Jiamo; Chen Huanwen

2012-01-01

Highlights: ► High throughput analysis of urinary creatinine is achieved by using ID-EESI–MS/MS. ► Urine sample is directly analyzed and no sample pre-treatment is required. ► Accurate quantification is accomplished with isotope dilution technique. - Abstract: Urinary creatinine (CRE) is an important biomarker of renal function. Fast and accurate quantification of CRE in human urine is required by clinical research. By using isotope dilution extractive electrospray ionization tandem mass spectrometry (EESI–MS/MS) a high throughput method for direct and accurate quantification of urinary CRE was developed in this study. Under optimized conditions, the method detection limit was lower than 50 μg L −1 . Over the concentration range investigated (0.05–10 mg L −1 ), the calibration curve was obtained with satisfactory linearity (R 2 = 0.9861), and the relative standard deviation (RSD) values for CRE and isotope-labeled CRE (CRE-d3) were 7.1–11.8% (n = 6) and 4.1–11.3% (n = 6), respectively. The isotope dilution EESI–MS/MS method was validated by analyzing six human urine samples, and the results were comparable with the conventional spectrophotometric method (based on the Jaffe reaction). Recoveries for individual urine samples were 85–111% and less than 0.3 min was taken for each measurement, indicating that the present isotope dilution EESI–MS/MS method is a promising strategy for the fast and accurate quantification of urinary CRE in clinical laboratories.

Application and evaluation of the mass spectrometric isotope dilution technique in the determination of rare earths in geological materials

International Nuclear Information System (INIS)

Moraes, N.M.P. de.

1988-01-01

Establishment of the experimental procedures employed in the rare earth element determination of geological samples by mass spectrometric isotope dilution analysis is discussed in the present work. The procedures involve preparation and calibration of the isotope tracers isotope dilution, dissolution in a teflon pressure vessel, chemical separation and isotope analysis using a fully automated Micromass VG ISOTOPES model 354 thermal ionization mass spectrometer. For the initial chemical separation of total rare earths the cationic resin was employed and HC1 and HNO 3 acids as eluents. In the second step rare earths elements were separated into individual (La, Ce and Nd) and subgroups (Sm-Eu-Gd, Yb-Er-Dy) fractions using the same cationic resin and α-HIBA as eluent. Nine elements La, Ce, Nd, Sm, Eu, Gd, Dy, Er and Yb are determined by this method in the ''United States Geological Survey'' (USGS) standard samples GSP-1, AGV-1 and G-2, with an overall precision of +- 1 to 2% and an accuracy of 5%. The concentration of rare earth element determined in the standard sample PCC-1 showed that the total analytical blanks are in submicrogram levels. The concentration of rare earth elements in the same USGS standard samples were also determined by Instrumental neutron activation analysis, neutron activation analysis with chemical separation before irradiation and inductively coupled argon plasma spectroscopy. The chemical procedures employed for these methods are the same as that used for mass spectrometric isotope dilution. Based on the results obtained, each method was evaluated pointing out their merits and defects. The study clearly showed that the chemical procedure employed for all these techniques was satisfactory. (author) [pt

A versatile method for simultaneous stable carbon isotope analysis of DNA and RNA nucleotides by liquid chromatography/isotope ratio mass spectrometry

NARCIS (Netherlands)

Moerdijk-Poortvliet, T.C.W.; Brasser, J.; de Ruiter, G.; Houtekamer, M.; Bolhuis, H.; Stal, L.J.; Boschker, H.T.S.

2014-01-01

RATIONALELiquid chromatography/isotope ratio mass spectrometry (LC/IRMS) is currently the most accurate and precise technique for the measurement of compound-specific stable carbon isotope ratios (C-13/C-12) in biological metabolites, at their natural abundance. However, until now this technique

Determination of thyroid hormones in placenta using isotope-dilution liquid chromatography quadrupole time-of-flight mass spectrometry.

Science.gov (United States)

Li, Zhong-Min; Giesert, Florian; Vogt-Weisenhorn, Daniela; Main, Katharina Maria; Skakkebæk, Niels Erik; Kiviranta, Hannu; Toppari, Jorma; Feldt-Rasmussen, Ulla; Shen, Heqing; Schramm, Karl-Werner; De Angelis, Meri

2018-01-26

The transplacental passage of thyroid hormones (THs) is of great significance since the maternal THs are vitally important in ensuring the normal fetal development. In this paper, we determined the concentrations of seven THs, viz. L-thyroxine (T 4 ), 3,3',5-triiodo-l-thyronine (T 3 ), 3,3',5'-triiodo-l-thyronine (rT 3 ), 3,3'-diiodo-l-thyronine (T 2 ), 3,5-diiodo-l-thyronine (rT 2 ), 3-iodo-l-thyronine (T 1 ) and 3-iodothyronamine (T 1 AM), in placenta using isotope dilution liquid chromatography quadrupole time-of-flight mass spectrometry. We optimized the method using isotopically labeled quantification standards ( 13 C 6 -T 4 , 13 C 6 -T 3 , 13 C 6 -rT 3 and 13 C 6 -T 2 ) and recovery standard ( 13 C 12 -T 4 ) in combination with solid-liquid extraction, liquid-liquid extraction and solid phase extraction. The linearity was obtained in the range of 0.5-150 pg uL -1 with R 2 values >0.99. The method detection limits (MDLs) ranged from 0.01 ng g -1 to 0.2 ng g -1 , while the method quantification limits (MQLs) were between 0.04 ng g -1 and 0.7 ng g -1 . The spike-recoveries for THs (except for T 1 and T 1 AM) were in the range of 81.0%-112%, with a coefficient of variation (CV) of 0.5-6.2%. The intra-day CVs and inter-day CVs were 0.5%-10.3% and 1.19%-8.88%, respectively. Concentrations of the THs were 22.9-35.0 ng g -1  T 4 , 0.32-0.46 ng g -1  T 3 , 2.86-3.69 ng g -1 rT 3 , 0.16-0.26 ng g -1  T 2 , and < MDL for other THs in five human placentas, and 2.05-3.51 ng g -1  T 4 , 0.37-0.62 ng g -1  T 3 , 0.96-1.3 ng g -1 rT 3 , 0.07-0.13 ng g -1  T 2 and < MDL for other THs in five mouse placentas. The presence of T 2 was tracked in placenta for the first time. This method with improved selectivity and sensitivity allows comprehensive evaluation of TH homeostasis in research of metabolism and effects of environmental contaminant exposures. Copyright © 2017 Elsevier B.V. All rights reserved.

Sensitive analysis of steroid estrogens and bisphenol a in small volumes of water using isotope-dilution ultra-performance liquid chromatography-tandem mass spectrometry.

Science.gov (United States)

Chang, Hong; Shen, Xiaoyan; Shao, Bing; Wu, Fengchang

2018-04-01

An isotope-dilution ultra-performance liquid chromatography-electrospray tandem mass spectrometry method combined with dansylation was established to sensitively quantify four steroid estrogens (estrone, 17α-estradiol, 17β-estradiol and 17α-ethynylestradiol) and bisphenol A in sewage influent and effluent. A simple hexane extraction was performed from a small volume (10 mL), followed by dansyl chloride derivatization and purification with a silica cartridge. The method effectively reduced the matrix effects in sample extract and permitted the selective and sensitive determination of target compounds from complicated matrices. The detection limits of the method for steroid estrogens were 0.20-0.90 ng L -1 in influent and 0.10-0.20 ng L -1 in effluent samples. For bisphenol A, the limits detection of the method were 20 and 0.80 for influent and effluent samples, respectively. Recoveries of 85%-96% were observed in all matrices. The method was applied to analyze residual estrogens and bisphenol A in sewage influent and effluent samples from Beijing, China. The concentrations of bisphenol A (636-1200 ng L -1 ) were up to 250 times higher than those of steroid estrogens. Estrone was the dominant estrogen in influent and effluent samples, while similar concentrations of 17α-estradiol and 17β-estradiol were detected in all samples. Copyright © 2018 Elsevier Ltd. All rights reserved.

Trace analysis of U, Th and other heavy metals in high purity aluminium with isotope dilution mass spectrometry

International Nuclear Information System (INIS)

Beer, B.; Heumann, K.G.

1992-01-01

A method for the determination of very low concentrations of U, Th, Fe, Zn, Tl, Cd, Cu and Ag in high purity aluminium with isotope dilution mass spectrometry (IDMS) is developed using a compact and cost-efficient thermal ionization quadrupole mass spectrometer. The detection limits obtained are (in ng/g):U=0.018, Th=0.06, Fe=82, Zn=86, Tl=0.2, Cd=4, Cu=1, Ag=2.6. By this method it is possible to determine the α-emitters U and Th in aluminium down to the sub-ng/g level with good precision of 0.4-10% and 0.5-5%, respectively. The results should also be accurate because IDMS is a reliable analytical method. The dissolution of aluminium is carried out by aqua regia followed by the trace/matrix separation and the isolation of the trace elements by anion exchange chromatography (U, Th, Zn, Tl, Cd), electrodeposition (Cu, Ag) and extraction (Fe). Different aluminium samples are analysed by IDMS and the results are compared with those of other methods. (orig.)

Direct quantification of creatinine in human urine by using isotope dilution extractive electrospray ionization tandem mass spectrometry

Energy Technology Data Exchange (ETDEWEB)

Li Xue [Institute of Environmental Pollution and Health, School of Environmental and Chemical Engineering, Shanghai University, Shanghai 200444 (China); Jiangxi Key Laboratory for Mass Spectrometry and Instrumentation, Applied Chemistry Department, East China Institute of Technology, Nanchang 330013 (China); Fang Xiaowei [Jiangxi Key Laboratory for Mass Spectrometry and Instrumentation, Applied Chemistry Department, East China Institute of Technology, Nanchang 330013 (China); Yu Zhiqiang; Sheng Guoying [Guangdong Key Laboratory of Environmental Protection and Resource Utilization, State Key Laboratory of Organic Geochemistry, Guangzhou Institute of Geochemistry, Chinese Academy of Sciences, Guangzhou 510640 (China); Wu Minghong [Shanghai Applied Radiation Institute, School of Environmental and Chemical Engineering, Shanghai University, Shanghai 200444 (China); Fu Jiamo [Institute of Environmental Pollution and Health, School of Environmental and Chemical Engineering, Shanghai University, Shanghai 200444 (China); Guangdong Key Laboratory of Environmental Protection and Resource Utilization, State Key Laboratory of Organic Geochemistry, Guangzhou Institute of Geochemistry, Chinese Academy of Sciences, Guangzhou 510640 (China); Chen Huanwen, E-mail: chw8868@gmail.com [Jiangxi Key Laboratory for Mass Spectrometry and Instrumentation, Applied Chemistry Department, East China Institute of Technology, Nanchang 330013 (China)

2012-10-20

Highlights: Black-Right-Pointing-Pointer High throughput analysis of urinary creatinine is achieved by using ID-EESI-MS/MS. Black-Right-Pointing-Pointer Urine sample is directly analyzed and no sample pre-treatment is required. Black-Right-Pointing-Pointer Accurate quantification is accomplished with isotope dilution technique. - Abstract: Urinary creatinine (CRE) is an important biomarker of renal function. Fast and accurate quantification of CRE in human urine is required by clinical research. By using isotope dilution extractive electrospray ionization tandem mass spectrometry (EESI-MS/MS) a high throughput method for direct and accurate quantification of urinary CRE was developed in this study. Under optimized conditions, the method detection limit was lower than 50 {mu}g L{sup -1}. Over the concentration range investigated (0.05-10 mg L{sup -1}), the calibration curve was obtained with satisfactory linearity (R{sup 2} = 0.9861), and the relative standard deviation (RSD) values for CRE and isotope-labeled CRE (CRE-d3) were 7.1-11.8% (n = 6) and 4.1-11.3% (n = 6), respectively. The isotope dilution EESI-MS/MS method was validated by analyzing six human urine samples, and the results were comparable with the conventional spectrophotometric method (based on the Jaffe reaction). Recoveries for individual urine samples were 85-111% and less than 0.3 min was taken for each measurement, indicating that the present isotope dilution EESI-MS/MS method is a promising strategy for the fast and accurate quantification of urinary CRE in clinical laboratories.

Improvement of accuracy for the quantitation of selenoproteins in post-column isotope dilution technique with HPLC ICP/MS

International Nuclear Information System (INIS)

Kim, Soo Jin; Pak, Yong Nam

2016-01-01

Post-column isotope dilution (PCID) or species-unspecific isotope dilution (ID) is a very useful quantitative technique in chromatography hyphenated with inductively coupled plasma–mass spectrometer (ICP/MS). In quantitative analysis, the calibration curve method is the most common one. However, it is not an absolute technique for the determination of concentration for the samples. ID method is the absolute one for the quantitative measurement technique, which means the quantity could be determined by the fundamental unit such as weight. To use the technique, it needs some requirements and there are several restrictions especially in the application for high-performance liquid chromatography (HPLC). The impurities in eluting solvent were in question. Thus, different purity of AA was examined and the result is shown in Figure 3. Figure 3(a) is the one for low (98%) and Figure 3(b) is high (99.999%) purity AA. The dotted area is for the eluting solvent. When low purity of 98% AA was introduced, the background was increasing while it remained the same for high-purity AA

Improvement of accuracy for the quantitation of selenoproteins in post-column isotope dilution technique with HPLC ICP/MS

Energy Technology Data Exchange (ETDEWEB)

Kim, Soo Jin; Pak, Yong Nam [Dept. of Chemistry Education, Korea National University of Education, Cheongju (Korea, Republic of)

2016-11-15

Post-column isotope dilution (PCID) or species-unspecific isotope dilution (ID) is a very useful quantitative technique in chromatography hyphenated with inductively coupled plasma–mass spectrometer (ICP/MS). In quantitative analysis, the calibration curve method is the most common one. However, it is not an absolute technique for the determination of concentration for the samples. ID method is the absolute one for the quantitative measurement technique, which means the quantity could be determined by the fundamental unit such as weight. To use the technique, it needs some requirements and there are several restrictions especially in the application for high-performance liquid chromatography (HPLC). The impurities in eluting solvent were in question. Thus, different purity of AA was examined and the result is shown in Figure 3. Figure 3(a) is the one for low (98%) and Figure 3(b) is high (99.999%) purity AA. The dotted area is for the eluting solvent. When low purity of 98% AA was introduced, the background was increasing while it remained the same for high-purity AA.

Liquid and gas chromatography coupled to isotope ratio mass spectrometry for the determination of 13C-valine isotopic ratios in complex biological samples

NARCIS (Netherlands)

Godin, Jean-Philippe; Breuillé, Denis; Obled, Christiane; Papet, Isabelle; Schierbeek, Henk; Hopfgartner, Gérard; Fay, Laurent-Bernard

2008-01-01

On-line gas chromatography-combustion-isotope ratio mass spectrometry (GC-C-IRMS) is commonly used to measure isotopic ratios at natural abundance as well as for tracer studies in nutritional and medical research. However, high-precision (13)C isotopic enrichment can also be measured by liquid

Determination of Trace Iron in Red Wine by Isotope Dilution Mass Spectrometry Using Multiple-Collector Inductively Coupled Plasma Mass Spectrometry

International Nuclear Information System (INIS)

Zhou Tao; Wang Jun; Lu Hai; Zhou Yuanjing; Li Haifeng

2009-01-01

This paper introduces determination of trace iron in red wine certified reference material by isotope dilution mass spectrometry (IDMS) method using a multiplecollector inductively coupled plasma mass spectrometry, equipped with a hexapole collision cell. The measurement procedure of iron isotopic abundance ratios was deeply researched. Reduced polyatomic ion interferences to iron isotopes ion by collision reaction using Ar and H 2 gas, high precise isotopic abundance ratios were achieved. Two relative measurement methods (ICP-MS and ICP-OES) were used to analyze trace iron in red wine. The results are compared with IDMS results, which indicate that they are accordant. The uncertainty analyses include each uncertainty factor in whole experiment and the uncertainty of used certified reference material and it shows that the procedure blank is not neglectable to detect limit and precision of the method. The establishment of IDMS method for analysis of trace iron in red wine supports the certification of certified reference materials. (authors)

Stable isotope dilution ultra-high performance liquid chromatography-tandem mass spectrometry quantitative profiling of tryptophan-related neuroactive substances in human serum and cerebrospinal fluid.

Science.gov (United States)

Hényková, Eva; Vránová, Hana Přikrylová; Amakorová, Petra; Pospíšil, Tomáš; Žukauskaitė, Asta; Vlčková, Magdaléna; Urbánek, Lubor; Novák, Ondřej; Mareš, Jan; Kaňovský, Petr; Strnad, Miroslav

2016-03-11

Many compounds related to L-tryptophan (L-TRP) have interesting biological or pharmacological activity, and their abnormal neurotransmission seems to be linked to a wide range of neurodegenerative and psychiatric diseases. A high-throughput method based on ultra-high performance liquid chromatography connected to electrospray tandem mass spectrometry (UHPLC-ESI-MS/MS) was developed for the quantitative analysis of L-TRP and 16 of its metabolites in human serum and cerebrospinal fluid (CSF), representing both major and minor routes of L-TRP catabolism. The combination of a fast LC gradient with selective tandem mass spectrometry enabled accurate analysis of almost 100 samples in 24h. The standard isotope dilution method was used for quantitative determination. The method's lower limits of quantification for serum and cerebrospinal fluid ranged from 0.05 to 15nmol/L and 0.3 to 45nmol/L, respectively. Analytical recoveries ranged from 10.4 to 218.1% for serum and 22.1 to 370.0% for CSF. The method's accuracy ranged from 82.4 to 128.5% for serum matrix and 90.7 to 127.7% for CSF matrix. All intra- and inter-day coefficients of variation were below 15%. These results demonstrate that the new method is capable of quantifying endogenous serum and CSF levels of a heterogeneous group of compounds spanning a wide range of concentrations. The method was used to determine the physiological levels of target analytes in serum and CSF samples from 18 individuals, demonstrating its reliability and potential usefulness in large-scale epidemiological studies. Copyright © 2016 Elsevier B.V. All rights reserved.

Isotope dilution analysis

Energy Technology Data Exchange (ETDEWEB)

Fudge, A.

1978-12-15

The following aspects of isotope dilution analysis are covered in this report: fundamental aspects of the technique; elements of interest in the nuclear field, choice and standardization of spike nuclide; pre-treatment to achieve isotopic exchange and chemical separation; sensitivity; selectivity; and accuracy.

Quantification of four major metabolites of embryotoxic N-methyl- and N-ethyl-2-pyrrolidone in human urine by cooled-injection gas chromatography and isotope dilution mass spectrometry.

Science.gov (United States)

Schindler, Birgit K; Koslitz, Stephan; Meier, Swetlana; Belov, Vladimir N; Koch, Holger M; Weiss, Tobias; Brüning, Thomas; Käfferlein, Heiko U

2012-04-17

N-Methyl- and N-ethyl-2-pyrollidone (NMP and NEP) are frequently used industrial solvents and were shown to be embryotoxic in animal experiments. We developed a sensitive, specific, and robust analytical method based on cooled-injection (CIS) gas chromatography and isotope dilution mass spectrometry to analyze 5-hydroxy-N-ethyl-2-pyrrolidone (5-HNEP) and 2-hydroxy-N-ethylsuccinimide (2-HESI), two newly identified presumed metabolites of NEP, and their corresponding methyl counterparts (5-HNMP, 2-HMSI) in human urine. The urine was spiked with deuterium-labeled analogues of these metabolites. The analytes were separated from urinary matrix by solid-phase extraction and silylated prior to quantification. Validation of this method was carried out by using both, spiked pooled urine samples and urine samples from 56 individuals of the general population with no known occupational exposure to NMP and NEP. Interday and intraday imprecision was better than 8% for all metabolites, while the limits of detection were between 5 and 20 μg/L depending on the analyte. The high sensitivity of the method enables us to quantify NMP and NEP metabolites at current environmental exposures by human biomonitoring.

Further development of IDGS: Isotope dilution gamma-ray spectrometry

International Nuclear Information System (INIS)

Li, T.K.; Parker, J.L.; Kuno, Y.; Sato, S.; Kamata, M.; Akiyama, T.

1991-01-01

The isotope dilution gamma-ray spectrometry (IDGS) technique for determining the plutonium concentration and isotopic composition of highly radioactive spent-fuel dissolver solutions has been further developed. Both the sample preparation and the analysis have been improved. The plutonium isotopic analysis is based on high-resolution, low-energy gamma-ray spectrometry. The plutonium concentration in the dissolver solutions then is calculated from the measured isotopic differences among the spike, the dissolver solution, and the spiked dissolver solution. Plutonium concentrations and isotopic compositions of dissolver solutions analyzed from this study agree well with those obtained by traditional isotope dilution mass spectrometry (IDMS) and are consistent with the first IDGS experimental result. With the current detector efficiency, sample size, and a 100-min count time, the estimated precision is ∼0.5% for 239 Pu and 240 Pu isotopic analyses and ∼1% for the plutonium concentration analysis. 5 refs., 2 figs., 7 tabs

Protein quantitation using Ru-NHS ester tagging and isotope dilution high-pressure liquid chromatography-inductively coupled plasma mass spectrometry determination.

Science.gov (United States)

Liu, Rui; Lv, Yi; Hou, Xiandeng; Yang, Lu; Mester, Zoltan

2012-03-20

An accurate, simple, and sensitive method for the direct determination of proteins by nonspecies specific isotope dilution and external calibration high-performance liquid chromatography-inductively coupled plasma mass spectrometry (HPLC-ICPMS) is described. The labeling of myoglobin (17 kDa), transferrin (77 kDa), and thyroglobulin (670 kDa) proteins was accomplished in a single-step reaction with a commercially available bis(2,2'-bipyridine)-4'-methyl-4-carboxybipyridine-ruthenium N-succinimidyl ester-bis(hexafluorophosphate) (Ru-NHS ester). Using excess amounts of Ru-NHS ester compared to the protein concentration at optimized labeling conditions, constant ratios for Ru to proteins were obtained. Bioconjugate solutions containing both labeled and unlabeled proteins as well as excess Ru-NHS ester reagent were injected onto a size exclusion HPLC column for separation and ICPMS detection without any further treatment. A (99)Ru enriched spike was used for nonspecies specific ID calibration. The accuracy of the method was confirmed at various concentration levels. An average recovery of 100% ± 3% (1 standard deviation (SD), n = 9) was obtained with a typical precision of better than 5% RSD at 100 μg mL(-1) for nonspecies specific ID. Detection limits (3SD) of 1.6, 3.2, and 7.0 fmol estimated from three procedure blanks were obtained for myoglobin, transferrin, and thyroglobulin, respectively. These detection limits are suitable for the direct determination of intact proteins at trace levels. For simplicity, external calibration was also tested. Good linear correlation coefficients, 0.9901, 0.9921, and 0.9980 for myoglobin, transferrin, and thyroglobulin, respectively, were obtained. The measured concentrations of proteins in a solution were in good agreement with their volumetrically prepared values. To the best of our knowledge, this is the first application of nonspecies specific ID for the accurate and direct determination of proteins using a Ru-NHS ester

Certification of mercury in acrylonitrile butadiene styrene by using isotope dilution mass spectrometry

International Nuclear Information System (INIS)

Hu Hai; Ma Liandi; Wei Chao; Zhou Tao; Wang Jun; Zhao Motian; Li Jinying

2008-01-01

Under the framework of a co-certification system for the development of Certified Reference Materials (CRMs) among China, Japan and Korea, the 1st co-certification campaign of mercury in acrylonitrile butadiene styrene (ABS) for Japanese CRMs was taken. In this campaign isotope dilution mass spectrometry (IDMS) was used. First, all abundances of Hg in spike 202 Hg, CRM and ABS were analyzed by MC-ICP-MS before the certification. Then the concentrations of 202 Hg and Hg in ABS were determined with IDMS by Q-ICP-MS. A new procedure to reduce memory effect was used. first, dilute with 5 μg/g Au solution for 1 min; then, 5 μg/g EDTA solution for 2 min. The results accord to each other very well and this implies that the co-certification system can run swimmingly. (authors)

Isotope dilution surface ionization mass spectrometry of silver in environmental materials

Energy Technology Data Exchange (ETDEWEB)

Murozumi, M; Nakamura, S; Suga, K [Muroran Inst. of Tech., Hokkaido (Japan)

1981-03-01

Surface ionization mass spectrometry has been developed to measure isotopic abundances and concentrations of silver in commercial high-purity metals, environmental materials such as rocks and plants, and /sup 109/Ag and /sup 107/Ag spikes. A minute amount of silver is extracted into a dithizone chloroform solution from a nitric acid solution of above samples. After the silver is back-extracted into 6.0 ml of a 7 mol/l HNO/sub 3/ solution, the solution is evaporated to dryness under the nitrogen atmosphere. Silver nitrate thus formed is dissolved in a mixture of 60 ..mu..l of an 0.003% silica gel suspended water and 5 ..mu..l of a 2% phosphoric acid. An aliquot of this solution is applied to the mass spectrometry using a rhenium single filament as an ion emitter. The proposed method can detect the presence of 10/sup -14/ g of silver on the ion emitter, and measure the /sup 109/Ag//sup 107/Ag isotopic ratio in environmental materials with the accuracy of 0.1 -- 0.2% in the coefficient of variation. Isotope dilution mass spectrometry using a /sup 107/Ag spike has revealed the silver concentration in the environmental standard materials, which were prepared by the National Bureau of Standards, U.S.A. and National Institute of Environmental Studies of Japan, as follows; 27.9 +- 0.2 ppb for the Orchard Leaves and 34.3 +- 0.3 ppb in the Pepper Bush. The determined values of silver in the Granodiorite, JG-1, and Basalt, JB-1 powders made by the Geological Survey of Japan are 25.4 +- 0.4 ppb and 41.3 +- 0.1 ppb respectively. Silver concentration in a coastal sea water sample is found to be at the level of 2.5 +- 0.4 ppt.

Precise determination of dissolved silica in seawater by ion-exclusion chromatography isotope dilution inductively coupled plasma mass spectrometry.

Science.gov (United States)

Nonose, Naoko; Cheong, Chikako; Ishizawa, Yukari; Miura, Tsutomu; Hioki, Akiharu

2014-08-20

Ion exclusion chromatograph (IEC) isotope dilution (ID) inductively coupled plasma mass spectrometry (ICP-MS) (IEC-ID-ICP-MS) was developed for measurement of dissolved silica in seawater, which was applied to production of certified reference materials (CRMs) of three concentration levels of nutrients (high, medium and low levels). IEC-ICP-MS has been employed to separate dissolved silica from seawater matrix. In the present study, in order to solve substantial problems due to spectral interference in ICP-MS and to improve the accuracy of IEC-ICP-MS beyond standard addition or conventional calibration methods, ID method was coupled with ICP-sector field mass spectrometry (operated under medium resolution,i.e., m/Δm=4000). In addition, effects of various operating parameters in ICP-MS on a silicon background level were also investigated to obtain lower background equivalent concentration (BEC). As a result, 3 ng g(-1) of the BEC and 0.5 % of relative standard uncertainties were achieved in the analyses of dissolved silica in seawater samples at concentration levels from 4.0 mg kg (-1) to 0.8 mg kg(-1) as silicon. The developed method was successfully validated by analyses of an artificial seawater containing a known amount of silicate and the seawater certified reference material MOOS-2 produced by the National Research Council Canada. Copyright © 2014 Elsevier B.V. All rights reserved.

Determination of steroid hormones in a human-serum reference material by isotope dilution--mass spectrometry: A candidate definitive method for cortisol

International Nuclear Information System (INIS)

Patterson, D.G.; Patterson, M.B.; Culbreth, P.H.; Fast, D.M.; Holler, J.S.; Sampson, E.J.; Bayse, D.D.

1984-01-01

We report a method, based on isotope dilution--mass spectrometry, for determining cortisol in a pooled specimen of human serum. Isotopically labeled cortisol is added to 5.0 mL of serum so that the molar concentrations of labeled cortisol and unlabeled cortisol are approximately equal. The specimen and two calibration standards are extracted with dichloromethane, and the extracted cortisol is converted to the methoxime-trimethylsilyl ether derivative. Samples and standards are analyzed by gas chromatography--mass spectrometry by monitoring the peak areas for m/z 605 and 608. The cortisol concentration is calculated by linear interpolation between the two bracketing standards. Variances of data collected during six weeks showed that the overall coefficient of variation (CV) was 0.69% (n . 32); the within-vial CV, 0.63%; the among-vial CV, 0.22%; and the among-day CV, 0.15% (means . 3.973 nmol/vial). Method specificity was demonstrated by liquid chromatographic as well as C 8 mini-column cleanup of samples before derivation, by alternative ion monitoring at m/z 636 and 639, and by negative-ion chemical ionization at m/z 459 and 462. Derivatives of all observed degradation products of cortisol under basic, neutral, and acidic conditions did not interfere

Isotope dilution/mass spectrometry of serum cholesterol with [3,4-13C]cholesterol: proposed definitive method

International Nuclear Information System (INIS)

Pelletier, O.; Wright, L.A.; Breckenridge, W.C.

1987-01-01

We describe a new gas-chromatographic/mass-spectrometric (GC/MS) isotope-dilution method for determination of serum cholesterol. The method has been fully optimized and documented to provide the high accuracy and precision expected for a Definitive Method. In the presence of [3,4- 13 C]cholesterol, cholesteryl esters in serum are hydrolyzed under optimum conditions and the entire cholesterol pool is extracted and derivatized to silyl ethers. The cholesterol derivatives are resolved from other sterols by gas-liquid chromatography on a fused silica column, and selected ions characteristic of cholesterol and the [3,4- 13 C]cholesterol are monitored with a GC/MS quandrupole system. We estimated the cholesterol content of samples by bracketing each sample with standards of comparable cholesterol concentration that also contained the [3,4- 13 C]cholesterol. The procedure was highly reproducible (CV less than 0.5%), better accuracy and precision being obtained with [3,4- 13 C]cholesterol than with heptadeuterated cholesterol. Mean values per gram of dry serum for one serum pool assayed by this method and that of the National Bureau of Standards differed by 0.5%. We conclude that the method satisfies the criteria for a Definitive Method

Uranium determination in sea water using the isotopic dilution technique and HR-ICPMS

International Nuclear Information System (INIS)

Pereira, Marcio Henrique da Costa; Sarkis, Jorge Eduardo de Souza; Hortellani, Marcos Antonio; Nascimento, Marcos R.L.

2009-01-01

In this work, the uranium total and the isotopic composition in seawater were calculated using the isotopic dilution applied to the mass spectrometry. The used tracer was a 233 U solution . Near 99 % of the present salts in the matrix were separated by evaporation up to the saturation point. The uranium present in aqueous phase was separated from the matrix through the ion exchange chromatography using the strong Dowex 1 x 8 200-400 mesh anionic resin in chloridric medium 12 M. The analyses were performed in a high resolution mass spectrometer with plasma inductively coupled source. The method validation was done using the seawater standard CASS-4 (Near shore Seawater Reference Material for Trace metals) produced by the NRC C. The procedure allowed to obtain the fractions exempt of salts, having as consequence a greater stability in the analytical signal, and a rise in the instrumental revenue for a great number of samples. The uranium found in the samples was present in levels considered naturals and were obtained with a precision near 2 %

Isotope Dilution - Thermal Ionisation Mass Spectrometric Analysis for Tin in a Fly Ash Material; Analisis de Estano en una Ceniza de Combustion mediante Espectrometria de Masas de Ionizacion Termica con Dilucion Isotopica

Energy Technology Data Exchange (ETDEWEB)

Hernandez, C; Fernandez, M; Quejido, A L

2006-07-01

Isotope dilution-thermal ionisation mass spectrometry (ID-TIMS) analysis has been applied to the determination of tin in a fly ash sample supplied by the EC Joint Research Centre (Ispra, Italy). The proposed procedure includes the silica gel/phosphoric acid technique for tin thermal ionisation activation and a strict heating protocol for isotope ratio measurements. Instrumental mass discrimination factor has been previously determined measuring a natural tin standard solution. Spike solutions has been prepared from 112Sn-enriched metal and quantified by reverse isotope dilution analysis. Two sample aliquots were spiked and tin was extracted with 4,5 M HCI during 25 min ultrasound exposure time. Due to the complex matrix of this fly ash material, a two-step purification stage using ion-exchange chromatography was required prior TIMS analysis. Obtained results for the two sample-spike blends (10,10 + - 0,55 y 10,50 + - 0,64 imolg-1) are comprarable, both value and uncertainty. Also a good reproducibility is observed between measurements. The proposed ID-TIMS procedure, as a primary method and due to the lack of fly ash reference material certified for tin content, can be used to validate more routine methodologies applied to tin determination in this kind of materials. (Author) 75 refs.

Quantification of acetylcholine, choline, betaine, and dimethylglycine in human plasma and urine using stable-isotope dilution ultra performance liquid chromatography-tandem mass spectrometry.

Science.gov (United States)

Kirsch, Susanne H; Herrmann, Wolfgang; Rabagny, Yannick; Obeid, Rima

2010-12-15

Disorders in choline metabolism are related to disease conditions. We developed a stable-isotope dilution ultra performance liquid chromatography-mass spectrometry (UPLC-MS/MS) method for the simultaneous quantification of acetylcholine (ACh), betaine, choline, and dimethylglycine (DMG). We used this method to measure concentrations of the analytes in plasma and urine in addition to other biological fluids after a protein precipitation by acetonitrile. The detection limits were between 0.35 nmol/L (for ACh in urine) and 0.34 μmol/L (for betaine in urine). ACh concentrations were not detectable in plasma. Intraassay and interassay coefficient of variation (CVs) were all DMG in cerebrospinal fluid (CV=12.44%). Mean recoveries in urine pool samples were between 99.2% and 103.9%. The urinary excretion of betaine, choline, and DMG was low, with approximately 50.0% higher excretion of choline in females compared to males. Median urinary excretion of ACh were 3.44 and 3.92 μmol/mol creatinine in males and females, respectively (p=0.689). Plasma betaine concentrations correlated significantly with urinary excretions of betaine (r=0.495, p=0.027) and choline (r=0.502, p=0.024) in females. Plasma choline concentrations correlated significantly with urinary excretion of ACh in males (r=0.419, p=0.041) and females (r=0.621, p=0.003). The new method for the simultaneous determination of ACh, betaine, choline, and DMG is sensitive, precise, and fast enough to be used in clinical investigations related to the methylation pathway. Copyright © 2010 Elsevier B.V. All rights reserved.

Isotope-dilution gas chromatography-mass spectrometry coupled with injection-port butylation for the determination of 4-t-octylphenol, 4-nonylphenols and bisphenol A in human urine.

Science.gov (United States)

Chung, Shuang-Hung; Ding, Wang-Hsien

2018-02-05

An analytical method that utilizes isotope-dilution gas chromatography-mass spectrometry (ID-GC-MS) coupled with injection-port butylation was developed. The method was validated, and confirmed to be able to determine the presence of three commonly detected endocrine-disrupting chemicals (EDCs: 4-tert-octylphenol (4-t-OP), 4-nonylphenols (4-NPs) and bisphenol A (BPA)) in human urine with high precision and accuracy. After sample preparation by solid-phase extraction, the extract was introduced into GC-MS via injection-port butylation. The butylated target analytes were identified and quantified by using ion-trap mass spectrometry operating in the selected-ion-storage mode, and employing the measurement of peak area ratios of the butylated target analytes and labeled-analogues in the samples and calibration standards. The labeled-analogues were also used to correct the variations associated with the analysis and matrix effect. The limits of quantitation (LOQs) ranged from 0.1 to 0.3ng/mL. High precisions for both intra- and inter-day analysis ranged from 1 to 6%, and excellent accuracy (mean recovery) ranged from 92 to 105% on two concentration levels. In human urine, the total concentrations of three selected EDCs varied from 1.28 to 7.14ng/mL. 4-NPs were detected within all collected samples. The developed method allows accurate analysis of trace-level of EDCs in urine, and these target EDCs could act as useful biomarkers to assess exposure in biomonitoring studies and programs. Copyright © 2017 Elsevier B.V. All rights reserved.

Isotope-dilution gas chromatography-mass spectrometry method for the analysis of hydroxyurea.

Science.gov (United States)

Garg, Uttam; Scott, David; Frazee, Clint; Kearns, Gregory; Neville, Kathleen

2015-06-01

Hydroxyurea is used in the treatment of various malignancies and sickle cell disease. There are limited studies on the pharmacokinetics of hydroxyurea, particularly in pediatric patients. An accurate, precise, and sensitive method is needed to support such studies and to monitor therapeutic adherence. We describe a novel gas chromatography-mass spectrometry (GC-MS) method for the determination of hydroxyurea concentration in plasma using stable labeled hydroxyurea C N2 as an internal standard. The method involved an organic extraction followed by the preparation of trimethylsilyl (TMS) derivatives of hydroxyurea for GC-MS selected ion-monitoring analysis. The following mass-to-charge (m/z) ratio ions for silated hydroxyurea and hydroxyurea C N2 were monitored: hydroxyurea-quantitative ion 277, qualifier ions 292 and 249; hydroxyurea C N2-quantitative ion 280, qualifier ion 295. This method was evaluated for reportable range, accuracy, within-run and between-run imprecisions, and limits of quantification. The reportable range for the method was 0.1-100 mcg/mL. All results were accurate within an allowable error of 15%. Within-run and between-run imprecisions were hydroxyurea described here is accurate, sensitive, precise, and robust. Its characteristics make the method suitable for supporting pharmacokinetic studies and/or clinical therapeutic monitoring.

Accurate determination and certification of bromine in plastic by isotope dilution inductively coupled plasma mass spectrometry

International Nuclear Information System (INIS)

Ohata, Masaki; Miura, Tsutomu

2014-01-01

Highlights: • Accurate analytical method of Br in plastic was studied by isotope dilution ICPMS. • A microwave acid digestion using quartz vessel was suitable for Br analysis. • Sample dilution by NH 3 solution could remove memory effect for ICPMS measurement. • The analytical result of the ID-ICPMS showed consistency with that of INAA. • The ID-ICPMS developed could apply to certification of Br in candidate plastic CRM. - Abstract: The accurate analytical method of bromine (Br) in plastic was developed by an isotope dilution inductively coupled plasma mass spectrometry (ID-ICPMS). The figures of merit of microwave acid digestion procedures using polytetrafluoroethylene (PTFE) or quartz vessels were studied and the latter one was suitable for Br analysis since its material was free from Br contamination. The sample dilution procedures using Milli-Q water or ammonium (NH 3 ) solution were also studied to remove memory effect for ICPMS measurement. Although severe memory effect was observed on Milli-Q water dilution, NH 3 solution could remove it successfully. The accuracy of the ID-ICPMS was validated by a certified reference material (CRM) as well as the comparison with the analytical result obtained by an instrumental neutron activation analysis (INAA) as different analytical method. From these results, the ID-ICPMS developed in the present study could be evaluated as accurate analytical method of Br in plastic materials and it could apply to certification of Br in candidate plastic CRM with respect to such regulations related to RoHS (restriction of the use of hazardous substances in electrical and electronics equipment) directive

Calibration and Data Processing in Gas Chromatography Combustion Isotope Ratio Mass Spectrometry

Science.gov (United States)

Zhang, Ying; Tobias, Herbert J.; Sacks, Gavin L.; Brenna, J. Thomas

2013-01-01

Compound-specific isotope analysis (CSIA) by gas chromatography combustion isotope ratio mass spectrometry (GCC-IRMS) is a powerful technique for the sourcing of substances, such as determination of the geographic or chemical origin of drugs and food adulteration, and it is especially invaluable as a confirmatory tool for detection of the use of synthetic steroids in competitive sport. We review here principles and practices for data processing and calibration of GCC-IRMS data with consideration to anti-doping analyses, with a focus on carbon isotopic analysis (13C/12C). After a brief review of peak definition, the isotopologue signal reduction methods of summation, curve-fitting, and linear regression are described and reviewed. Principles for isotopic calibration are considered in the context of the Δ13C = δ13CM – δ13CE difference measurements required for establishing adverse analytical findings for metabolites relative to endogenous reference compounds. Considerations for the anti-doping analyst are reviewed. PMID:22362612

An application of nitrogen microwave-induced plasma mass spectrometry to isotope dilution analysis of selenium in marine organisms

Energy Technology Data Exchange (ETDEWEB)

Shirasaki, Toshihiro [Hitachi Instruments Engineering Co. Ltd., Hitachinaka, Ibaraki (Japan); Yoshinaga, Jun; Morita, Masatoshi; Okumoto, Toyoharu; Oishi, Konosuke

1996-01-01

Nitrogen microwave-induced plasma mass spectrometry was studied for its applicability to the isotope dilution analysis of selenium in biological samples. Spectroscopic interference by calcium, which is present in high concentrations in biological samples, was investigated. No detectable background spectrum was observed for the major selenium isotopes of {sup 78}Se and {sup 80}Se. No detectable interferences by sodium, potassium, calcium and phosphorus on the isotope ratio {sup 80}Se/{sup 78}Se were observed up to concentration of 200 mg/ml. The method was applied to the analysis of selenium in biological reference materials of marine organisms. The results showed good agreement between the certified and found values. (author).

Steroid isotopic standards for gas chromatography-combustion isotope ratio mass spectrometry (GCC-IRMS).

Science.gov (United States)

Zhang, Ying; Tobias, Herbert J; Brenna, J Thomas

2009-03-01

Carbon isotope ratio (CIR) analysis of urinary steroids using gas chromatography-combustion isotope ratio mass spectrometry (GCC-IRMS) is a recognized test to detect illicit doping with synthetic testosterone. There are currently no universally used steroid isotopic standards (SIS). We adapted a protocol to prepare isotopically uniform steroids for use as a calibrant in GCC-IRMS that can be analyzed under the same conditions as used for steroids extracted from urine. Two separate SIS containing a mixture of steroids were created and coded CU/USADA 33-1 and CU/USADA 34-1, containing acetates and native steroids, respectively. CU/USADA 33-1 contains 5alpha-androstan-3beta-ol acetate (5alpha-A-AC), 5alpha-androstan-3alpha-ol-17-one acetate (androsterone acetate, A-AC), 5beta-androstan-3alpha-ol-11, 17-dione acetate (11-ketoetiocholanolone acetate, 11k-AC) and 5alpha-cholestane (Cne). CU/USADA 34-1 contains 5beta-androstan-3alpha-ol-17-one (etiocholanolone, E), 5alpha-androstan-3alpha-ol-17-one (androsterone, A), and 5beta-pregnane-3alpha, 20alpha-diol (5betaP). Each mixture was prepared and dispensed into a set of about 100 ampoules using a protocol carefully designed to minimize isotopic fractionation and contamination. A natural gas reference material, NIST RM 8559, traceable to the international standard Vienna PeeDee Belemnite (VPDB) was used to calibrate the SIS. Absolute delta(13)C(VPDB) and Deltadelta(13)C(VPDB) values from randomly selected ampoules from both SIS indicate uniformity of steroid isotopic composition within measurement reproducibility, SD(delta(13)C)<0.2 per thousand. This procedure for creation of isotopic steroid mixtures results in consistent standards with isotope ratios traceable to the relevant international reference material.

Gluconeogenesis from labeled carbon: estimating isotope dilution

International Nuclear Information System (INIS)

Kelleher, J.K.

1986-01-01

To estimate the rate of gluconeogenesis from steady-state incorporation of labeled 3-carbon precursors into glucose, isotope dilution must be considered so that the rate of labeling of glucose can be quantitatively converted to the rate of gluconeogenesis. An expression for the value of this isotope dilution can be derived using mathematical techniques and a model of the tricarboxylic acid (TCA) cycle. The present investigation employs a more complex model than that used in previous studies. This model includes the following pathways that may affect the correction for isotope dilution: 1) flux of 3-carbon precursor to the oxaloacetate pool via acetyl-CoA and the TCA cycle; 2) flux of 4- or 5-carbon compounds into the TCA cycle; 3) reversible flux between oxaloacetate (OAA) and pyruvate and between OAA and fumarate; 4) incomplete equilibrium between OAA pools; and 5) isotope dilution of 3-carbon tracers between the experimentally measured pool and the precursor for the TCA-cycle OAA pool. Experimental tests are outlined which investigators can use to determine whether these pathways are significant in a specific steady-state system. The study indicated that flux through these five pathways can significantly affect the correction for isotope dilution. To correct for the effects of these pathways an alternative method for calculating isotope dilution is proposed using citrate to relate the specific activities of acetyl-CoA and OAA

Environmental application of elemental speciation analysis based on liquid or gas chromatography hyphenated to inductively coupled plasma mass spectrometry-A review

International Nuclear Information System (INIS)

Popp, Maximilian; Hann, Stephan; Koellensperger, Gunda

2010-01-01

In recent years the number of environmental applications of elemental speciation analysis using inductively coupled plasma mass spectrometry (ICP-MS) as detector has increased significantly. The analytical characteristics, such as extremely low detection limits (LOD) for almost all elements, the wide linear range, the possibility for multi-elemental analysis and the possibility to apply isotope dilution mass spectrometry (IDMS) make ICP-MS an attractive tool for elemental speciation analysis. Two methodological approaches, i.e. the combination of ICP-MS with high performance liquid chromatography (HPLC) and gas chromatography (GC), dominate the field. Besides the investigation of metals and metalloids and their species (e.g. Sn, Hg, As), representing 'classic' elements in environmental science, more recently other elements (e.g. P, S, Br, I) amenable to ICP-MS determination were addressed. In addition, the introduction of isotope dilution analysis and the development of isotopically labeled species-specific standards have contributed to the success of ICP-MS in the field. The aim of this review is to summarize these developments and to highlight recent trends in the environmental application of ICP-MS coupled to GC and HPLC.

The IDA-80 measurement evaluation programme on mass spectrometric isotope dilution analysis of uranium and plutonium. Vol. 1

International Nuclear Information System (INIS)

Beyrich, W.; Golly, W.; Spannagel, G.; Kernforschungszentrum Karlsruhe G.m.b.H.; Bievre, P. de; Wolters, W.

1984-12-01

The main objective was the acquisition of basic data on the uncertainties involved in the mass spectrometric isotope dilution analysis as applied to the determination of uranium and plutonium in active feed solutions of reprocessing plants. The element concentrations and isotopic compositions of all test materials used were determined by CBNM and NBS with high accuracy. The more than 60000 analytical data reported by the participating laboratories were evaluated by statistical methods applied mainly to the calculation of estimates of the variances for the different uncertainty components contributing to the total uncertainty of this analytical technique. Attention was given to such topics as sample ageing, influence of fission products, spike calibration, ion fractionation, Pu-241 decay correction, minor isotope measurement and errors in data transfer. Furthermore, the performance of the 'dried sample' technique and the 'in-situ' spiking method of undiluted samples of reprocessing fuel solution with U-235/Pu-242 metal alloy spikes, were tested successfully. Considerable improvement of isotope dilution analysis in this safeguards relevant application during the last decade is shown as compared to the results obtained in the IDA-72 interlaboratory experiment, organized by KfK in 1972 on the same subject. (orig./HP) [de

Application of isotope dilution for the determination of thorium in biological samples by inductively coupled plasma mass spectrometry

International Nuclear Information System (INIS)

Igarashi, Yasuhito; Shiraishi, Kunio; Takaku, Yuichi; Masuda, Kimihiko; Seki, Riki; Yamamoto, Masayoshi.

1992-01-01

The applicability of isotope dilution-inductively coupled plasma mass spectrometry (ID-ICP-MS) was examined for Th in biological samples. A naturally occurring isotope of Th(Th-230) was used as the spiking isotope. The concentration of Th-230 in the final sample solution was about 50 - 60 pg/ml; an isotope ratio of 232/230 could be measured with a relative standard deviation of less than 2%. The error magnification depended on the amount of Th-232 being concomitant with the Th-230. Though it was shown that one ng of Th-232 could be determined with reasonable precision with a tracer of the present purity, more care should be taken to reduce any source of systematic error. (author)

The interlaboratory experiment IDA-72 on mass spectrometric isotope dilution analysis. Vol. 2

International Nuclear Information System (INIS)

Beyrich, W.; Drosselmeyer, E.

1975-07-01

Volume II of the report on the IDA-72 experiment contains papers written by different authors on a number of special topics connected with the preparation, performance and evaluation of the interlaboratory test. In detail the sampling procedures for active samples of the reprocessing plant and the preparation of inactive reference and spike solution from standard material are described as well as new methods of sample conditioning by evaporation. An extra chapter is devoted to the chemical sample treatment as a preparation for mass spectrometric analysis of the U and Pu content of the solutions. Special topics are also methods for mass discrimination corrections, α-spectrometer measurements as a supplement for the determination of Pu-238 and the comparison of concentration determinations by mass spectrometric isotope dilution analysis with those performed by X-ray fluorescence spectrometry. The last part of this volume contains papers connected with the computerized statistical evaluation of the high number of data. (orig.) [de

The interlaboratory experiment IDA-72 on mass spectrometric isotope dilution analysis. Vol. 1

International Nuclear Information System (INIS)

Beyrich, W.; Drosselmeyer, E.

1975-07-01

Within the framework of the Safeguards Project of the Federal Republic of Germany at the Nuclear Research Center Karlsruhe an analytical intercomparison program was carried out in cooperation with 22 laboratories of 13 countries or international organizations. The main objective was the acquisition of basic data on the errors involved in the mass spectrometric isotope dilution analysis if it is applied to the determination of uranium and plutonium in diluted active feed solutions of reprocessing plants in routine operation. The results were evaluated by statistical methods mainly in regard to the calculation of the estimates of the variances for the different error components contributing to the total error of this analytical technique. Furthermore, the performance of two new methods for sample conditioning suggested by the International Atomic Energy Agency, Vienna, and the European Institute for Transuranium Elements (EURATOM), Karlsruhe, was successfully tested. The results of some investigations on the stability of diluted high active feed solutions and on comparison analysis by X-ray fluorescence spectrometry are also included. Data on the analytical efforts (manhours) invested in this study are reported as well as general experiences made in the organization and performance of an experiment on such an extended international level. (orig.) [de

Evaluation of gas chromatography-combustion-isotope ratio mass spectrometry (GC-C-IRMS) for the quality assessment of citrus liqueurs.

Science.gov (United States)

Schipilliti, Luisa; Bonaccorsi, Ivana; Cotroneo, Antonella; Dugo, Paola; Mondello, Luigi

2013-02-27

Citrus liqueurs are alcoholic beverages obtained by maceration. The European Parliament protects these alcoholic beverages, forbidding the addition of nature-identical flavoring substances. However, for economical and technological reasons, producers often add natural and/or synthetic flavors to the alcoholic syrup, obtaining artificial spirit drinks. The aim of this study is to investigate the authenticity of Italian liqueurs, of lemon, bergamot, and mandarin (locally known as "limoncello", "bargamino", and "mandarinetto"), comparing the carbon isotope ratios with values determined in genuine cold-pressed peel oils. Authenticity assessment was performed using headspace-solid phase microextraction coupled to gas chromatography-combustion-isotope ratio mass spectrometry. Additional analyses were performed by direct enantioselective gas chromatography to determine the enantiomeric distribution of selected chiral volatiles and by gas chromatography-mass spectrometry for the qualitative analyses of the samples. The method allowed confirmation of genuineness. Enantioselective gas chromatography analyses confirmed the results, demonstrating the reliability of the method.

Accurate determination and certification of bromine in plastic by isotope dilution inductively coupled plasma mass spectrometry

Energy Technology Data Exchange (ETDEWEB)

Ohata, Masaki, E-mail: m-oohata@aist.go.jp; Miura, Tsutomu

2014-07-21

Highlights: • Accurate analytical method of Br in plastic was studied by isotope dilution ICPMS. • A microwave acid digestion using quartz vessel was suitable for Br analysis. • Sample dilution by NH{sub 3} solution could remove memory effect for ICPMS measurement. • The analytical result of the ID-ICPMS showed consistency with that of INAA. • The ID-ICPMS developed could apply to certification of Br in candidate plastic CRM. - Abstract: The accurate analytical method of bromine (Br) in plastic was developed by an isotope dilution inductively coupled plasma mass spectrometry (ID-ICPMS). The figures of merit of microwave acid digestion procedures using polytetrafluoroethylene (PTFE) or quartz vessels were studied and the latter one was suitable for Br analysis since its material was free from Br contamination. The sample dilution procedures using Milli-Q water or ammonium (NH{sub 3}) solution were also studied to remove memory effect for ICPMS measurement. Although severe memory effect was observed on Milli-Q water dilution, NH{sub 3} solution could remove it successfully. The accuracy of the ID-ICPMS was validated by a certified reference material (CRM) as well as the comparison with the analytical result obtained by an instrumental neutron activation analysis (INAA) as different analytical method. From these results, the ID-ICPMS developed in the present study could be evaluated as accurate analytical method of Br in plastic materials and it could apply to certification of Br in candidate plastic CRM with respect to such regulations related to RoHS (restriction of the use of hazardous substances in electrical and electronics equipment) directive.

The potential of Isotope Ratio Mass Spectrometry (IRMS) and gas chromatography-IRMS analysis of triacetone triperoxide in forensic explosives investigations

NARCIS (Netherlands)

Bezemer, K.D.B.; Koeberg, M.; Heijden, A.E.D.M. van der; Driel, C.A. va; Blaga, C.; Bruinsma, J.; Asten, A.C. van

2016-01-01

Studying links between triacetone triperoxide (TATP) samples from crime scenes and suspects can assist in criminal investigations. Isotope ratio mass spectrometry (IRMS) and gas chromatography (GC)-IRMS were used to measure the isotopic compositions of TATP and its precursors acetone and hydrogen

Determination of ultratrace levels of tributyltin in waters by isotope dilution and gas chromatography coupled to tandem mass spectrometry.

Science.gov (United States)

Rodríguez-Cea, Andrés; Rodríguez-González, Pablo; Font Cardona, Nuria; Aranda Mares, José Luís; Ballester Nebot, Salomé; García Alonso, J Ignacio

2015-12-18

The current EU legislation lays down the Environmental Quality Standards (EQS) of 45 priority substances in surface water bodies. In particular, the concentration of tributyltin (TBT) must not exceed 0.2ngL(-1) and analytical methodologies with a Limit of Quantification (LOQ) equal or below 0.06ngL(-1) are urged to be developed. This work presents a procedure for the determination of ultratrace levels of TBT in water samples by Isotope Dilution and GC-MS/MS operating in Selected Reaction Monitoring (SRM) mode which meets current EU requirements. The method requires the monitorization of five consecutive transitions (287>175 to 291>179) for the sensitive and selective detection of TBT. The measured isotopic distribution of TBT fragment ions was in agreement with the theoretical values computed by a polynomial expansion algorithm. The combined use of Tandem Mass Spectrometry, a sample volume of 250mL, the preconcentration of 1mL of organic phase to 30μL and an injection volume of 25μL by Programmed Temperature Vaporization provided a LOQ of 0.0426ngL(-1) for TBT (calculated as ten times the standard deviation of nine independent blanks). The recovery for TBT calculated in Milli-Q water at the EQS level was 106.3±4%. A similar procedure was also developed for the quantification of dibutyltin (DBT) and monobutyltin (MBT) in water samples showing satisfactory results. The method was finally implemented in a routine testing laboratory to demonstrate its applicability to real samples obtaining quantitative recoveries for TBT at the EQS level in mineral water, river water and seawater. Copyright © 2015 Elsevier B.V. All rights reserved.

Measurement of Muscle Protein Fractional Synthetic Rate by Capillary Gas Chromatography/Combustion Isotope Ratio Mass Spectrometry

OpenAIRE

Yarasheski, Kevin E.; Smith, Kenneth; Rennie, Michael J.; Bier, Dennis M.

1992-01-01

The measurement of skeletal muscle protein fractional synthetic rate using an infusion of (1-13C)leucine and measuring the isotopic abundance of the tracer in skeletal muscle protein by preparative gas chromatography (GC)/ninhydrin isotope ratio mass spectrometry (IRMS) is laborious and subject to errors owing to contamination by 12C. The purpose of this study was to compare muscle (13C)leucine enrichment measured with the conventional preparative GC/ninhydrin IRMS approach to a new, continuo...

A novel quantification strategy of transferrin and albumin in human serum by species-unspecific isotope dilution laser ablation inductively coupled plasma mass spectrometry (ICP-MS)

Energy Technology Data Exchange (ETDEWEB)

Feng, Liuxing, E-mail: fenglx@nim.ac.cn; Zhang, Dan; Wang, Jun; Shen, Dairui; Li, Hongmei

2015-07-16

Highlights: • Species-unspecific ID-PAGE-LA-ICP-MS was used to quantify Alb and Tf in human serum. • Addition methods of species-unspecific {sup 34}S spike were evaluated. • Isotope change conditions were investigated to reach satisfactory “isotope equilibration”. • Human serum CRM (ERM-DA470k/IFCC) was used to validate the new arrangements. • The developed method offers potential for accurate quantification of protein by ID-PAGE-LA-ICP-MS. - Abstract: Species-specific (SS) isotope dilution analysis with gel electrophoresis (GE)-laser ablation (LA)-ICP-MS is a promising technique for the quantification of particular metal-binding proteins in biological samples. However, unavailable isotopically enriched spike and metal losses in GE separation are main limitations for SS-isotope dilution PAGE-LA-ICP-MS. In this study, we report for the first time the absolute quantification of transferrin (Tf) and albumin (Alb) in human serum by non-denaturing (native) GE combined with species-unspecific isotope dilution mass spectrometry (IDMS). In order to achieve a homogeneous distribution of both protein and isotope-enriched spike (simulated isotope equilibration), immersing the protein strips with {sup 34}S spike solution after gel electrophoresis was demonstrated to be an effective way of spike addition. Furthermore, effects of immersion time and {sup 34}S spike concentration were investigated to obtain optimal conditions of the post-electrophoresis isotope dilution method. The relative mass of spike and ablated sample (m{sub sp}/m{sub sam}) in IDMS equation was calculated by standard Tf and Alb proteins, which could be applied to the quantification of Tf and Alb in ERM-DA470k/IFCC for method confirmation. The results were in agreement with the certified value with good precision and small uncertainty (1.5–3%). In this method, species-specific spike protein is not necessary and the integrity of the heteroatom-protein could be maintained in sample preparation

A novel quantification strategy of transferrin and albumin in human serum by species-unspecific isotope dilution laser ablation inductively coupled plasma mass spectrometry (ICP-MS)

International Nuclear Information System (INIS)

Feng, Liuxing; Zhang, Dan; Wang, Jun; Shen, Dairui; Li, Hongmei

2015-01-01

Highlights: • Species-unspecific ID-PAGE-LA-ICP-MS was used to quantify Alb and Tf in human serum. • Addition methods of species-unspecific 34 S spike were evaluated. • Isotope change conditions were investigated to reach satisfactory “isotope equilibration”. • Human serum CRM (ERM-DA470k/IFCC) was used to validate the new arrangements. • The developed method offers potential for accurate quantification of protein by ID-PAGE-LA-ICP-MS. - Abstract: Species-specific (SS) isotope dilution analysis with gel electrophoresis (GE)-laser ablation (LA)-ICP-MS is a promising technique for the quantification of particular metal-binding proteins in biological samples. However, unavailable isotopically enriched spike and metal losses in GE separation are main limitations for SS-isotope dilution PAGE-LA-ICP-MS. In this study, we report for the first time the absolute quantification of transferrin (Tf) and albumin (Alb) in human serum by non-denaturing (native) GE combined with species-unspecific isotope dilution mass spectrometry (IDMS). In order to achieve a homogeneous distribution of both protein and isotope-enriched spike (simulated isotope equilibration), immersing the protein strips with 34 S spike solution after gel electrophoresis was demonstrated to be an effective way of spike addition. Furthermore, effects of immersion time and 34 S spike concentration were investigated to obtain optimal conditions of the post-electrophoresis isotope dilution method. The relative mass of spike and ablated sample (m sp /m sam ) in IDMS equation was calculated by standard Tf and Alb proteins, which could be applied to the quantification of Tf and Alb in ERM-DA470k/IFCC for method confirmation. The results were in agreement with the certified value with good precision and small uncertainty (1.5–3%). In this method, species-specific spike protein is not necessary and the integrity of the heteroatom-protein could be maintained in sample preparation process. Moreover, the

Stable isotope dilution quantification of mutagens in cooked foods by combined liquid chromatography-thermospray mass spectrometry

International Nuclear Information System (INIS)

Yamaizumi, Ziro; Kasai, Hiroshi; Nishimura, Susumu; Edmonds, C.G.; McCloskey, J.A.

1986-01-01

A method of general applicability for the detection and quantification of mutagens in cooked foods at the ppb level is presented. A minimal sample prefractionation is employed and [Me- 2 H 3 ]-labeled analogs of the compounds of interest are added for identification and quantification of mutagens by accurate measurement of chromatographic retention (K') in reverse-phase high-performance liquid chromatography (HPLC), and by measurement of the ratio of response of the protonated molecular ions of analyte and internal standard by directly coupled liquid chromatography-mass spectrometry (LC/MS). Initial application is demonstrated in the analysis of 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) and 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MelQ) in broiled salmon. (Auth.)

Measurement of isotope abundance variations in nature by gravimetric spiking isotope dilution analysis (GS-IDA).

Science.gov (United States)

Chew, Gina; Walczyk, Thomas

2013-04-02

Subtle variations in the isotopic composition of elements carry unique information about physical and chemical processes in nature and are now exploited widely in diverse areas of research. Reliable measurement of natural isotope abundance variations is among the biggest challenges in inorganic mass spectrometry as they are highly sensitive to methodological bias. For decades, double spiking of the sample with a mix of two stable isotopes has been considered the reference technique for measuring such variations both by multicollector-inductively coupled plasma mass spectrometry (MC-ICPMS) and multicollector-thermal ionization mass spectrometry (MC-TIMS). However, this technique can only be applied to elements having at least four stable isotopes. Here we present a novel approach that requires measurement of three isotope signals only and which is more robust than the conventional double spiking technique. This became possible by gravimetric mixing of the sample with an isotopic spike in different proportions and by applying principles of isotope dilution for data analysis (GS-IDA). The potential and principle use of the technique is demonstrated for Mg in human urine using MC-TIMS for isotopic analysis. Mg is an element inaccessible to double spiking methods as it consists of three stable isotopes only and shows great potential for metabolically induced isotope effects waiting to be explored.

Determination of Cd and Pb in human blood by isotope dilution inductively coupled plasma mass spectrometry : International comparison

International Nuclear Information System (INIS)

Park, Chang Joon; Suh, Jeong Ki; Lee, Sang Hwa

1996-01-01

Inorganic analytical laboratory of Korea Research Institute of Standards and Science participated in an interlaboratory comparison program operated by Quebec Toxicology Centre of Canada in 1994 and again in 1995. The objective of this program is to enable participating laboratories to assess reproducibility and accuracy of their analytical results for trace toxic elements in human biological fluids. This laboratory determined Cd and Pb concentrations in 3 levels of human blood samples by isotope dilution inductively coupled plasma mass spectrometry. 0.5 mL of blood sample is added to the digestion bomb together with 2 mL of nitric acid and enriched spike isotopes and then decomposed in the microwave digestion system. The decomposed sample is diluted to 10 mL and nebulized into ICP-MS. The Cd and Pb values reported by all participating laboratories are presented and compared. The values reported by this laboratory are within the acceptable range of target values. (author)

Simultaneous speciation of mercury and butyltin compounds in natural waters and snow by propylation and species-specific isotope dilution mass spectrometry analysis

Energy Technology Data Exchange (ETDEWEB)

Monperrus, M.; Tessier, E.; Veschambre, S.; Amouroux, D.; Donard, O. [Universite de Pau et des Pays de L' Adour, Laboratoire de Chimie Analytique Bio-inorganique et Environnement, CNRS UMR 5034, Helioparc, Pau (France)

2005-02-01

A robust method has been developed for simultaneous determination of mercury and butyltin compounds in aqueous samples. This method is capable of providing accurate results for analyte concentrations in the picogram per liter to nanogram per liter range. The simultaneous determination of the mercury and tin compounds is achieved by species-specific isotope dilution, derivatization, and gas chromatography-inductively coupled plasma mass spectrometer (GC-ICP-MS). In derivatization by ethylation and propylation, reaction conditions such as pH and the effect of chloride were carefully studied. Ethylation was found to be more sensitive to matrix effects, especially for mercury compounds. Propylation was thus the preferred derivatization method for simultaneous determination of organomercury and organotin compounds in environmental samples. The analytical method is highly accurate and precise, with RSD values of 1 and 3% for analyte concentrations in the picogram per liter to nanogram per liter range. By use of cleaning procedures and SIDMS blank measurements, detection limits in the range 10-60 pg L{sup -1} were achieved; these are suitable for determination of background levels of these contaminants in environmental samples. This was demonstrated by using the method for analysis of real snow and seawater samples. This work illustrates the great advantage of species-specific isotope dilution for the validation of an analytical speciation method - the possibility of overcoming species transformations and non-quantitative recovery. Analysis time is saved by use of the simultaneous method, because of the use of a single sample-preparation procedure and one analysis. (orig.)

Development of SI-traceable C-peptide certified reference material NMIJ CRM 6901-a using isotope-dilution mass spectrometry-based amino acid analyses.

Science.gov (United States)

Kinumi, Tomoya; Goto, Mari; Eyama, Sakae; Kato, Megumi; Kasama, Takeshi; Takatsu, Akiko

2012-07-01

A certified reference material (CRM) is a higher-order calibration material used to enable a traceable analysis. This paper describes the development of a C-peptide CRM (NMIJ CRM 6901-a) by the National Metrology Institute of Japan using two independent methods for amino acid analysis based on isotope-dilution mass spectrometry. C-peptide is a 31-mer peptide that is utilized for the evaluation of β-cell function in the pancreas in clinical testing. This CRM is a lyophilized synthetic peptide having the human C-peptide sequence, and contains deamidated and pyroglutamylated forms of C-peptide. By adding water (1.00 ± 0.01) g into the vial containing the CRM, the C-peptide solution in 10 mM phosphate buffer saline (pH 6.6) is reconstituted. We assigned two certified values that represent the concentrations of total C-peptide (mixture of C-peptide, deamidated C-peptide, and pyroglutamylated C-peptide) and C-peptide. The certified concentration of total C-peptide was determined by two amino acid analyses using pre-column derivatization liquid chromatography-mass spectrometry and hydrophilic chromatography-mass spectrometry following acid hydrolysis. The certified concentration of C-peptide was determined by multiplying the concentration of total C-peptide by the ratio of the relative area of C-peptide to that of the total C-peptide measured by liquid chromatography. The certified value of C-peptide (80.7 ± 5.0) mg/L represents the concentration of the specific entity of C-peptide; on the other hand, the certified value of total C-peptide, (81.7 ± 5.1) mg/L can be used for analyses that does not differentiate deamidated and pyroglutamylated C-peptide from C-peptide itself, such as amino acid analyses and immunochemical assays.

Urinary detection of conjugated and unconjugated anabolic steroids by dilute-and-shoot liquid chromatography-high resolution mass spectrometry.

Science.gov (United States)

Tudela, Eva; Deventer, Koen; Geldof, Lore; Van Eenoo, Peter

2015-02-01

Anabolic androgenic steroids (AAS) are an important class of doping agents. The metabolism of these substances is generally very extensive and includes phase-I and phase-II pathways. In this work, a comprehensive detection of these metabolites is described using a 2-fold dilution of urine and subsequent analysis by liquid chromatography-high resolution mass spectrometry (LC-HRMS). The method was applied to study 32 different metabolites, excreted free or conjugated (glucuronide or sulfate), which permit the detection of misuse of at least 21 anabolic steroids. The method has been fully validated for 21 target compounds (8 glucuronide, 1 sulfate and 12 free steroids) and 18 out of 21 compounds had detection limits in the range of 1-10 ng mL(-1) in urine. For the conjugated compounds, for which no reference standards are available, metabolites were synthesized in vitro or excretion studies were investigated. The detection limits for these compounds ranged between 0.5 and 18 ng mL(-1) in urine. The simple and straightforward methodology complements the traditional methods based on hydrolysis, liquid-liquid extraction, derivatization and analysis by gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry (LC-MS). Copyright © 2014 John Wiley & Sons, Ltd.

Multiresidue analysis of persistent organic pollutants in contaminated soil using GC-LRMS, GC-HRMS and isotope dilution analysis

International Nuclear Information System (INIS)

Badea, Silviu-Laurentiu; Lundstedt, Staffan; Liljelind, Per; Tysklind, Mats

2009-01-01

In this study we evaluated a multiresidue analytical protocol for selected Persistent Organic Pollutants (POPs) in soil, that later can be used in adsorption and leaching studies. The method used was based on Soxhlet extraction and open column chromatographic fractionation and clean-up, as well as liquid-liquid extraction and acetylation for phenolic compounds. Target analytes, i.e. polychlorinated phenols (PCPhs), hexachlorobenzene (HCB), polychlorinated dibenzodioxins and furans (PCDDs/Fs), polychlorinated biphenyl (PCBs) PAHs, were detected and quantified using Gas Chromatography-Low Resolution Mass Spectrometry (GC-LRMS) and Gas Chromatography-High Resolution Mass Spectrometry (GC-HRMS) and isotope dilution methodology. Generally, the results show a good recovery and a low standard deviation for those isomers that have also a 13 C labeled compound present in the sample: 4-mono, 2,4 di, 2,4,5 tri, 2,3,4,5 and penta chlorinated phenols. Our results clearly demonstrate that it is possible to analyse a wide range of compounds in complex soil matrixes. (authors(

Reverse isotope dilution method for determining benzene and metabolites in tissues

International Nuclear Information System (INIS)

Bechtold, W.E.; Sabourin, P.J.; Henderson, R.F.

1988-01-01

A method utilizing reverse isotope dilution for the analysis of benzene and its organic soluble metabolites in tissues of rats and mice is presented. Tissues from rats and mice that had been exposed to radiolabeled benzene were extracted with ethyl acetate containing known, excess quantities of unlabeled benzene and metabolites. Butylated hydroxytoluene was added as an antioxidant. The ethyl acetate extracts were analyzed with semipreparative reversed-phase HPLC. Isolated peaks were collected and analyzed for radioactivity (by liquid scintillation spectrometry) and for mass (by UV absorption). The total amount of each compound present was calculated from the mass dilution of the radiolabeled isotope. This method has the advantages of high sensitivity, because of the high specific activity of benzene, and relative stability of the analyses, because of the addition of large amounts of unlabeled carrier analogue

The isotope separation by ion exchange chromatography. Application to the lithium isotopes separation; La separation isotopique par chromatographie ionique

Energy Technology Data Exchange (ETDEWEB)

Albert, M G; Barre, Y; Neige, R

1994-12-31

In this work is described the used study step to demonstrate the industrial feasibility of a lithium isotopes separation process by ion exchange chromatography. After having recalled how is carried out the exchange reaction between the lithium isotopes bound on the cations exchanger resin and those which are in solution and gave the ion exchange chromatography principle, the authors establish a model which takes into account the cascade theory already used for enriched uranium production. The size parameters of this model are: the isotopic separation factor (which depends for lithium of the ligands nature and of the coordination factor), the isotopic exchange kinetics and the mass flow (which depends of the temperature, the lithium concentration, the resins diameter and the front advance). The way they have to be optimized and the implementation of the industrial process are given. (O.M.). 5 refs.

Isotope-dilution analyses of the metallic elements

International Nuclear Information System (INIS)

Chastagner, P.

1982-01-01

The isotope-dilution mass spectroscopy (IDMS) technique has proven to be to be a reliable, versatile analytical tool. Its applications seem to be limited only by the ingenuity of the investigator. Among its advantages are: small sample size; general applicability; precision and accuracy; dynamic range; simplified chemistry; determination is fixed at the time and place of isotopic homogenization. The last listed item is especially important for nuclear safeguards and processes where inventories are critical. IDMS is now a routine analytical technique in geochemical and nuclear laboratories, and in many environmental laboratories. Microgram and nanogram samples are normally used, frequently with automatic mass spectrometers, in many of these routine applications. More advanced techniques permit picogram and sub picogram samples to be analyzed, and spike to sample ratios can range from 1:1 to 1:10 12 with detection limits at attogram levels for some elements. 3 figures, 3 tables

Isotope dilution analysis for urinary fentanyl and its main metabolite, norfentanyl, in patients by isotopic fractionation using capillary gas chromatography

Energy Technology Data Exchange (ETDEWEB)

Sera, Shoji; Goromaru, Tsuyoshi [Fukuyama Univ., Hiroshima (Japan). Faculty of Pharmacy and Pharmaceutical Sciences; Sameshima, Teruko; Kawasaki, Koichi; Oda, Toshiyuki

1998-07-01

Isotope dilution analysis was applied to determine urinary excretion of fentanyl (FT) and its main metabolite, norfentanyl (Nor-FT), by isotopic fractionation using a capillary gas chromatograph equipped with a surface ionization detector (SID). Urinary FT was determined quantitatively in the range of 0.4-40 ng/ml using deuterium labeled FT (FT-{sup 2}H{sub 19}), as an internal standard. We also performed isotope dilution analysis of Nor-FT in urine. N-Alkylation was necessary to sensitively detect Nor-FT with SID. Methyl derivative was selected from 3 kinds of N-alkyl derivatives to increase sensitivity and peak resolution, and to prevent interference with urinary compound. Nor-FT concentration was quantitatively determined in the range of 10-400 ng/ml using deuterium labeled Nor-FT (Nor-FT-{sup 2}H{sub 10}). No endogenous compounds or concomitant drugs interfered with the detection of FT and Nor-FT in the urine of patients. The present method will be useful for pharmacokinetic studies and the evaluation of drug interactions in FT metabolism. (author)

Isotope dilution analysis for urinary fentanyl and its main metabolite, norfentanyl, in patients by isotopic fractionation using capillary gas chromatography

International Nuclear Information System (INIS)

Sera, Shoji; Goromaru, Tsuyoshi; Sameshima, Teruko; Kawasaki, Koichi; Oda, Toshiyuki

1998-01-01

Isotope dilution analysis was applied to determine urinary excretion of fentanyl (FT) and its main metabolite, norfentanyl (Nor-FT), by isotopic fractionation using a capillary gas chromatograph equipped with a surface ionization detector (SID). Urinary FT was determined quantitatively in the range of 0.4-40 ng/ml using deuterium labeled FT (FT- 2 H 19 ), as an internal standard. We also performed isotope dilution analysis of Nor-FT in urine. N-Alkylation was necessary to sensitively detect Nor-FT with SID. Methyl derivative was selected from 3 kinds of N-alkyl derivatives to increase sensitivity and peak resolution, and to prevent interference with urinary compound. Nor-FT concentration was quantitatively determined in the range of 10-400 ng/ml using deuterium labeled Nor-FT (Nor-FT- 2 H 10 ). No endogenous compounds or concomitant drugs interfered with the detection of FT and Nor-FT in the urine of patients. The present method will be useful for pharmacokinetic studies and the evaluation of drug interactions in FT metabolism. (author)

Direct measurement of burn up monitor by Pulsed Laser Deposition (PLD) followed by Isotopic Dilution Mass Spectrometry

International Nuclear Information System (INIS)

Sajimol, R.; Manoravi, P.; NaIini, S.; Balasubramanian, R.; Joseph, M.

2012-01-01

Burn-up measurement is an important aspect in the assessment of fuel performance especially for experimental nuclear fuels. Conventional mass spectrometric technique offer the best accuracy for determination of burn-up but they suffer from the labour intensive and time consuming chemical separation procedures followed by mass spectrometric analysis. Our laboratory has reported a potential laser mass spectrometric technique with advantages of (i) direct and fast measurement of ion intensities of selected rare earth element and residual heavy element atoms to deduce burn up and (ii) adaptability to remote handling of radioactive samples. Direct quantification of burn up monitor element in fuel in the form of pellet as well as liquid was probed by pulsed laser deposition followed by Isotopic Dilution Mass Spectrometric technique (IDMS). The procedure involving laser ablation of heavy element (namely U and Pu) and fission product (Nd, La etc) from a simulated spent fuel matrix followed by isotopic dilution mass spectrometry using thermal ionization mass spectrometry (TIMS) has been presently attempted to arrive at the rare earth element to heavy element ratio to deduce burn up using the methodology described in our earlier work. The details of IDMS technique has been reviewed by Heumann et al. Accurately weighed amounts of major rare earth fission products such as Nd, La, Ce and Sm in solution form were mixed with known quantity of uranium solution (all the weights are corresponding to their fission yields and the residual heavy element atoms after a given burn up) and mixed together to attain uniformity. The solution is then dried and resulting powder was pelletized and sintered. Subsequently, the pellet was ablated with pulsed laser (8 ns, 532 nm, Nd-YAG) and the plume was deposited on a glass plate. This deposit was dissolved in minimum amount of nitric acid. A known volume of the solution was mixed with spike (for e.g., 150 Nd/ 142 Nd, 233 U/ 238 U in this study

A STUDY ON CARBON ISOTOPE OF CO2 AND CH4 IN WESTERN DIENG PLATEU BY GAS CHROMATOGRAPHY- ISOTOPE RATIO MASS SPECTROMETER (GC-IRMS

Directory of Open Access Journals (Sweden)

Hanik Humaida

2010-06-01

Full Text Available The carbon isotope can be used to evaluate volcanism phenomenon of volcano. The study of carbon isotope of CO2 and CH4 was carried out in western Dieng Plateau by mass-spectrometer. Before analysis, sampel was separated by gas chromatography using a Porapak-Q column and a FID (Flame Ionization Detector detector. The gas was oxidized by copper oxide at 850oC before being ionized in mass-spectrometer for isotope analysis. The CO2 content in Candradimuka crater (-4.10 O/OO, indicated that the gas may be as volcanic gas. The other CO2 from Sumber and western Gua Jimat, had isotope value  of -10.05 and -12.07 O/OO, respectively, indicating contamination from crustal and subduction material. The carbon isotope of CH4 gas from Pancasan village was -63.42 O/OO, that may be categorized as biogenic gas.   Keywords: isotope, CO2, CH4, Dieng.

Burn-up determination of irradiated thoria samples by isotope dilution-thermal ionisation mass spectrometry

International Nuclear Information System (INIS)

Aggarwal, S.K.; Jaison, P.G.; Telmore, V.M.; Shah, R.V.; Sant, V.L.; Sasibhushan, K.; Parab, A.R.; Alamelu, D.

2010-03-01

Burn-up was determined experimentally using thermal ionization mass spectrometry for two samples from ThO 2 bundles irradiated in KAPS-2. This involved quantitative dissolution of the irradiated fuel samples followed by separation and determination of Th, U and a stable fission product burn-up monitor in the dissolved fuel solution. Stable fission product 148 Nd was used as a burn-up monitor for determining the number of fissions. Isotope Dilution-Thermal Ionisation Mass Spectrometry (ID-TIMS) using natural U, 229 Th and enriched 142 Nd as spikes was employed for the determination of U, Th and Nd, respectively. Atom % fission values of 1.25 ± 0.03 were obtained for both the samples. 232 U content in 233 U determined by alpha spectrometry was about 500 ppm and this was higher by a factor of 5 compared to the theoretically predicted value by ORIGEN-2 code. (author)

Isotope dilution liquid chromatography-tandem mass spectrometry for simultaneous identification and quantification of beta-casomorphin 5 and beta-casomorphin 7 in yoghurt.

Science.gov (United States)

Nguyen, D D; Solah, V A; Johnson, S K; Charrois, J W A; Busetti, F

2014-03-01

A highly selective and sensitive liquid chromatography-tandem mass spectrometry method was developed and validated for the simultaneous identification and quantification of beta-casomorphin 5 (BCM5) and beta-casomorphin 7 (BCM7) in yoghurt. The method used deuterium labelled BCM5-d10 and BCM7-d10 as surrogate standards for confident identification and accurate and quantification of these analytes in yoghurt. Linear responses for BCM5 and BCM7 (R(2)=0.9985 and 0.9986, respectively) was observed in the range 0.01-10ng/μL. The method limits of detection (MLDs) in yoghurt extracts were found to be 0.5 and 0.25ng/g for BCM5 and BCM7, respectively. Analyses of spiked samples were used to provide confirmation of accuracy and precision of the analytical method. Recoveries relative to the surrogate standards of these spikes were in the range of 95-106% for BCM5 and 103-109% for BCM7. Precision from analysis of spiked samples was expressed as relative standard deviation (%RSD) and values were in the range 1-16% for BCM5 and 1-6% for BCM7. Inter-day reproducibility was between 2.0-6.4% for BCM5 and between 3.2-6.1% for BCM7. The validated isotope dilution LC-MS/MS method was used to measure BCM5 and BCM7 in ten commercial and laboratory prepared samples of yoghurt and milk. Neither BCM5 nor BCM7 was detected in commercial yoghurts. However, they were observed in milk and laboratory prepared yoghurts and interestingly their levels decreased during processing. BCM5 decreased from 1.3ng/g in milk to 1.1ng/g in yoghurt made from that milk at 0day storage and

Isotope dilution inductively coupled plasma mass spectrometry (ID ICP-MS) for the certification of lead and cadmium in environmental standard reference materials.

Science.gov (United States)

Murphy, K E; Beary, E S; Rearick, M S; Vocke, R D

2000-10-01

Lead (Pb) and cadmium (Cd) have been determined in six new environmental standard reference materials (SRMs) using isotope dilution inductively coupled plasma mass spectrometry (ID ICP-MS). The SRMs are the following: SRM 1944, New York-New Jersey Waterway Sediment, SRMs 2583 and 2584, Trace Elements in Indoor Dust, Nominal 90 mg/kg and 10,000 mg/kg Lead, respectively, SRMs 2586 and 2587, Trace Elements in Soil Containing Lead from Paint, Nominal 500 mg/kg and 3,000 mg/kg Lead, respectively, and SRM 2782, Industrial Sludge. The capabilities of ID ICP-MS for the certification of Pb and Cd in these materials are assessed. Sample preparation and ratio measurement uncertainties have been evaluated. Reproducibility and accuracy of the established procedures are demonstrated by determination of gravimetrically prepared primary standard solutions and by comparison with isotope dilution thermal ionization mass spectrometry (ID TIMS). Material heterogeneity was readily demonstrated to be the dominant source of uncertainty in the certified values.

The analysis study of plutonium in the environmental sample by mass spectrum combined with isotopic dilution

International Nuclear Information System (INIS)

Han Jun; Fu Zhonghua; Mao Xingen; Meng Fanben

2004-01-01

The technology of the rhenium filament carbonization was used to increase the ionization efficiency in this paper. The plutonium in the environmental sample was analyzed by Mass Spectrum combined with isotope dilution. Analysis of the 239 Pu blank in the process: The analysis of 239 Pu from the chemical process was carried out in order to establish the influence of the 239 Pu introduced from the process. The analysis results were shown in Table 1 sample 1 was not gone through the process, sample 2 and sample 3 were gone through the process. It was clear that there was no influence of the 239 Pu from the process within the deviation. Results and Discussions: The environmental samples which were dealed with the chemical method were prepared the sample of mass spectrum, The atomic ratio of the 239 Pu and 242 Pu in the environmental samples was measured by Mass Spectrum. The atomic ratio in the tracer 242 Pu was 0.01476±0.00007.The results for nuclide content in environment were given in Table 2. The content of 239 Pu in the tracer was high, so the existing of 239 Pu in the environmental samples can be determined by the changing of the atomic ratio of 242 Pu to 239 Pu. It was clear that there was 239 Pu in the environmental samples except the cypress leaves-2 and the pine leaves-3 within the deviation, and the content of 239 Pu were given in Table 2. Conclusion: a. Plutonium was separated and purified from the impurity by the anion-exchange and the electrodeposition, it was possible to provide the eligible mass spectrum sample. b. The measurement of plutonium in the environmental samples was not influenced by the flow of the background in the experiment. c. As the technology of the rhenium carbonization was used to increase the ionization efficiency, the content of plutonium which was about 10 -13 g in the environmental sample could be quantitatively analyzed by Mass Spectrum combined with isotope dilution. (authors)

Isotope correlation and mass spectrometry techniques for irradiated fuel assay

International Nuclear Information System (INIS)

Deron, S.

1985-01-01

This paper outlines the methods used to account for fissionable materials in irradiated nuclear fuel elements entering reprocessing plants. Verification is accomplished at three mass balance stations in the plant. Techniques employed fall into two categories: isotopic and isotope dilution analyses by mass spectometry and isotope correlation techniques. These methods are discussed in some detail

Quantification of fentanyl in serum by isotope dilution analysis using capillary gas chromatography

Energy Technology Data Exchange (ETDEWEB)

Sera, Shoji; Goromaru, Tsuyoshi [Fukuyama Univ., Hiroshima (Japan); Sameshima, Teruko; Kawasaki, Koichi; Oda, Toshiyuki

1998-06-01

The quantitative determination of fentanyl (FT) in serum was examined by isotope dilution analysis using a capillary gas chromatograph equipped with a surface ionization detector. The separation of FT and its deuterated analogue, FT-{sup 2}H{sub 19}, was achieved within 15 min a column temperature of 260degC by using a 25 m column. Measurement of the samples prepared by the addition of a known amount of FT in the range of 0.2 to 40 ng/ml with 20 ng/ml of FT-{sup 2}H{sub 19} to human control serum allowed observation of a linear relationship between the peak area ratio and the added amount ratio. The correlation coefficient obtained by regression analysis was 0.999. The advantage of the present isotope dilution method was demonstrated by comparison with other FT analogues which substituted a propionyl group with an acetyl group or a phenethyl group with a benzyl group as the internal standard. The present method was used to determine the serum level of FT in surgical patients after i.v. administration. No endogenous compounds and concomitant drugs interfered with the detection of FT or FT-{sup 2}H{sub 19}. This method was considered to be useful for the pharmacokinetic study of FT in patients. (author)

Quantification of fentanyl in serum by isotope dilution analysis using capillary gas chromatography

International Nuclear Information System (INIS)

Sera, Shoji; Goromaru, Tsuyoshi; Sameshima, Teruko; Kawasaki, Koichi; Oda, Toshiyuki

1998-01-01

The quantitative determination of fentanyl (FT) in serum was examined by isotope dilution analysis using a capillary gas chromatograph equipped with a surface ionization detector. The separation of FT and its deuterated analogue, FT- 2 H 19 , was achieved within 15 min a column temperature of 260degC by using a 25 m column. Measurement of the samples prepared by the addition of a known amount of FT in the range of 0.2 to 40 ng/ml with 20 ng/ml of FT- 2 H 19 to human control serum allowed observation of a linear relationship between the peak area ratio and the added amount ratio. The correlation coefficient obtained by regression analysis was 0.999. The advantage of the present isotope dilution method was demonstrated by comparison with other FT analogues which substituted a propionyl group with an acetyl group or a phenethyl group with a benzyl group as the internal standard. The present method was used to determine the serum level of FT in surgical patients after i.v. administration. No endogenous compounds and concomitant drugs interfered with the detection of FT or FT- 2 H 19 . This method was considered to be useful for the pharmacokinetic study of FT in patients. (author)

Compound-Specific Chlorine Isotope Analysis of Tetrachloromethane and Trichloromethane by Gas Chromatography-Isotope Ratio Mass Spectrometry vs Gas Chromatography-Quadrupole Mass Spectrometry: Method Development and Evaluation of Precision and Trueness.

Science.gov (United States)

Heckel, Benjamin; Rodríguez-Fernández, Diana; Torrentó, Clara; Meyer, Armin; Palau, Jordi; Domènech, Cristina; Rosell, Mònica; Soler, Albert; Hunkeler, Daniel; Elsner, Martin

2017-03-21

Compound-specific chlorine isotope analysis of tetrachloromethane (CCl 4 ) and trichloromethane (CHCl 3 ) was explored by both, gas chromatography-isotope ratio mass spectrometry (GC-IRMS) and GC-quadrupole MS (GC-qMS), where GC-qMS was validated in an interlaboratory comparison between Munich and Neuchâtel with the same type of commercial GC-qMS instrument. GC-IRMS measurements analyzed CCl isotopologue ions, whereas GC-qMS analyzed the isotopologue ions CCl 3 , CCl 2 , CCl (of CCl 4 ) and CHCl 3 , CHCl 2 , CHCl (of CHCl 3 ), respectively. Lowest amount dependence (good linearity) was obtained (i) in H-containing fragment ions where interference of 35 Cl- to 37 Cl-containing ions was avoided; (ii) with tuning parameters favoring one predominant rather than multiple fragment ions in the mass spectra. Optimized GC-qMS parameters (dwell time 70 ms, 2 most abundant ions) resulted in standard deviations of 0.2‰ (CHCl 3 ) and 0.4‰ (CCl 4 ), which are only about twice as large as 0.1‰ and 0.2‰ for GC-IRMS. To compare also the trueness of both methods and laboratories, samples from CCl 4 and CHCl 3 degradation experiments were analyzed and calibrated against isotopically different reference standards for both CCl 4 and CHCl 3 (two of each). Excellent agreement confirms that true results can be obtained by both methods provided that a consistent set of isotopically characterized reference materials is used.

Mass spectrometric isotope dilution analyses of palladium, silver, cadmium and tellurium in carbonaceous chondrites

International Nuclear Information System (INIS)

Loss, R.D.; Rosman, K.J.R.; De Laeter, J.

1984-01-01

The mass spectrometric isotope dilution technique was used to measure the elemental abundances of Pd, Ag, Cd and Te in Orgueil (C1), Ivuna (C1), Murray (C2) and Allende (C3) chondrites. The Pd abundance of 554 ppb for the Cl chondrites is almost identical to the recommended value of Anders and Ebihara (1982); that for Cd (712 ppb) is approximately 5% higher, whereas that for Ag (198 ppb) is approximately 10% lower than the recommended values. A smooth distribution for the abundances of the odd-A nuclides between 65 128 Te and 130 Te to lie approximately 30% above the r-process peak at A = 130, whereas the new value fits smoothly into the general trend. (author)

Isotopic Abundance and Chemical Purity Analysis of Stable Isotope Deuterium Labeled Sudan I

Directory of Open Access Journals (Sweden)

CAI Yin-ping;LEI Wen;ZHENG Bo;DU Xiao-ning

2014-02-01

Full Text Available It is important that to analysis of the isotopic abundance and chemical purity of Sudan I-D5, which is the internal standard of isotope dilution mass spectrometry. The isotopic abundance of Sudan I-D5 is detected by “mass cluster” classification method and LC-MS. The repeatability and reproducibility experiments were carried out by using different mass spectrometers and different operators. The RSD was less than 0.1%, so the repeatability and reproducibility were satisfactory. The accuracy and precision of the isotopic abundance analysis method was good with the results of F test and t test. The high performance liquid chromatography (HPLC had been used for detecting the chemical purity of Sudan I-D5 as external standard method.

Gas chromatography/isotope ratio mass spectrometry: analysis of methanol, ethanol and acetic acid by direct injection of aqueous alcoholic and acetic acid samples.

Science.gov (United States)

Ai, Guomin; Sun, Tong; Dong, Xiuzhu

2014-08-15

Methanol, ethanol, and acetic acid are not easily extracted from aqueous samples and are susceptible to isotope fractionation in gas chromatography/isotope ratio mass spectrometry (GC/IRMS) analysis. Developing a direct dilution GC/IRMS method for aqueous samples, by adjusting the sample concentrations in common solvents to be similar to each other and using a fixed GC split ratio, is very convenient and important because any linearity effects caused by amount-dependent isotope fractionation can be avoided. The suitability of acetonitrile and acetone solvents for the GC/IRMS analysis of pure methanol, ethanol and acetic acid, and commercial liquor and vinegar samples was evaluated using n-hexane and water as control solvents. All the solvents including water were separated from the analyte on a HP-INNOWAX column and were diverted away from the combustion interface. The influence of liquor matrix on the ethanol GC/IRMS analyses was evaluated by adding pure ethanol to liquor samples. Acetonitrile and acetone gave similar δ(13) C values for pure ethanol and pure acetic acid to those obtained in water and n-hexane, and also gave similar δ(13) C values of ethanol in liquor and acetic acid in white vinegar to that obtained in water. For methanol analysis, acetonitrile and refined acetone gave similar δ(13) C values to that obtained in water, but n-hexane was not a suitable solvent. In addition, isotopic fractionation caused by solvent and solute interactions was observed. We recommend using acetonitrile for the GC/IRMS analysis of aqueous alcoholic samples, and acetone for the analysis of aqueous acetic acid samples. This direct dilution method can provide high accurate and precise GC/IRMS analysis of the relative changes in δ(13) C values of methanol, ethanol, and acetic acid. Copyright © 2014 John Wiley & Sons, Ltd.

Simultaneous measurement of total Estradiol and Testosterone in human serum by isotope dilution liquid chromatography tandem mass spectrometry

Science.gov (United States)

Zhou, Hui; Wang, Yuesong; Gatcombe, Matthew; Farris, Jacob; Botelho, Julianne C.; Caudill, Samuel P.; Vesper, Hubert W.

2017-01-01

Reliable measurement of total testosterone and estradiol is critical for their use as biomarkers of hormone related disorders in patient care and translation research. We developed and validated a mass spectrometry method to simultaneously quantify these analytes in human serum without chemical derivatization. Serum is equilibrated with isotopic internal standards and treated with acidic buffer to release hormones from their binding proteins. Lipids are isolated and polar impurities are removed by two serial liquid-liquid extraction steps. Total testosterone and estradiol are measured using liquid chromatography tandem mass spectrometry (LC-MS/MS) in combination of positive and negative electrospray ionization modes. The method shows broad analytical measurement range for both testosterone 0.03–48.5 nM (0.75–1400 ng/dL) and estradiol 11.0–5138 pM (2.99–1400 pg/mL) and excellent agreement with certified reference materials (mean bias less than 2.1% to SRM 971, BCR 576, 577, and 578) and a high order reference method (mean bias 1.25% for testosterone and −0.84% for estradiol). The high accuracy of the method was monitored and certified by CDC Hormone Standardization (HoSt) Program for two years with mean bias −0.7% (95%CI: −1.6% to 0.2%) for testosterone and 0.1% (95%CI: −2.2% to 2.3%) for estradiol. The method precision over a 2-year period for Quality Control pools at low, medium and high concentrations was 2.7–2.9% for testosterone and 3.3–5.3% for estradiol. With the consistently excellent accuracy and precision, this method is readily applicable for high-throughput clinical and epidemiological studies. PMID:28801832

The isotope separation by ion exchange chromatography. Application to the lithium isotopes separation

International Nuclear Information System (INIS)

Albert, M.G.; Barre, Y.; Neige, R.

1993-01-01

In this work is described the used study step to demonstrate the industrial feasibility of a lithium isotopes separation process by ion exchange chromatography. After having recalled how is carried out the exchange reaction between the lithium isotopes bound on the cations exchanger resin and those which are in solution and gave the ion exchange chromatography principle, the authors establish a model which takes into account the cascade theory already used for enriched uranium production. The size parameters of this model are: the isotopic separation factor (which depends for lithium of the ligands nature and of the coordination factor), the isotopic exchange kinetics and the mass flow (which depends of the temperature, the lithium concentration, the resins diameter and the front advance). The way they have to be optimized and the implementation of the industrial process are given. (O.M.)

Quantification of urinary 0,0'-dityrosine, a biomarker for oxidative damage to proteins, by high performance liquid chromatography with triple quadrupole tandem mas spectrometry. A comparison with ion-trap tandem mass spectrometry.

NARCIS (Netherlands)

Orhan, H.; Coolen, S.; Meerman, J.H.N.

2005-01-01

We recently described an isotope dilution reversed-phase liquid chromatography-atmospheric pressure chemical ionization-ion-trap-tandem mass spectrometry (HPLC-APCI-MS/MS) method for the quantitative determination of oxidized amino acids in human urine, including o,o′-dityrosine, a specific marker

Novel method for measurement of glutathione kinetics in neonates using liquid chromatography coupled to isotope ratio mass spectrometry

NARCIS (Netherlands)

Schierbeek, Henk; te Braake, Frans; Godin, Jean-Philippe; Fay, Laurent-Bernard; van Goudoever, Johannes B.

2007-01-01

A novel analytical method using liquid chromatography coupled to isotope ratio mass spectrometry (LC/IRMS) was developed for measuring the fractional synthesis rate (FSR) of glutathione (GSH) in neonates after infusion of [1-(13)C]-glycine as a tracer. After transformation of GSH into GSSG, its

ISOTOPE-DILUTION AMMONIA CHEMICAL-IONIZATION MASS FRAGMENTOGRAPHIC ANALYSIS OF URINARY 3-O-METHYLATED CATECHOLAMINE METABOLITES - RAPID SAMPLE CLEANUP BY DERIVATIZATION AND EXTRACTION OF LYOPHILIZED SAMPLES

NARCIS (Netherlands)

KEMA, IP; MEIBORG, G; NAGEL, GT; STOB, GJ; MUSKIET, FAJ

1993-01-01

We developed a method for simultaneous quantification of the urinary 3-O-methylated catecholamine metabolites 3-methoxytyramine, normetanephrine and metanephrine by stable isotope-dilution ammonia chemical ionization mass fragmentography. Prepurification of lyophilized samples was done by

Determination of the interchangeable heavy-metal fraction in soils by isotope dilution mass spectrometry

International Nuclear Information System (INIS)

Gaebler, H.E.; Bahr, A.; Mieke, B.

1999-01-01

An isotope dilution technique using enriched stable isotopes is applied to determine the interchangeable heavy-metal fraction in soils. Metals in two soil samples are extracted at constant pH, with water, NH 4 NO 3 , and EDTA. A spike of enriched stable isotopes is added to the suspension of sample and eluant at the beginning of the extraction. The heavy-metal fraction which exchanges with the added spike during the extraction is called the interchangeable fraction. The extractable heavy-metal fractions are obtained from the heavy-metal concentrations in the eluates. Isotope ratios and concentrations are determined by HR-ICP-MS. The isotope dilution technique described enables both the extractable and the interchangeable heavy-metal fractions to be determined in the same experiment. The combination of both results gives additional information on elemental availability under different conditions that cannot be obtained by analyzing the extractable heavy-metal fractions alone. It is demonstrated that in some cases different eluants just shift the distribution of the interchangeable fraction of an element between the solid and liquid phases (e.g., Pb and Cd in a topsoil sample) while the amount of the interchangeable fraction itself remains constant. For other elements, as Ni, Zn, and Cr, the use of different eluants (different pH, complexing agents) sometimes enlarges the interchangeable fraction. (orig.)

Determination of cadmium, lead and zinc in a candidate reference materials using isotope dilution mass spectrometry

International Nuclear Information System (INIS)

Munoz, Luis; Gras, Nuri; Quejido, Alberto; Fernandez, Marta

2001-01-01

The growing demands placed on analytical laboratories to ensure the reliability of their results, due to the introduction of systems of quality and to the increasing use of metrology in chemical measurements has led most laboratories to validate their methodologies and to control them statistically. One of the techniques used most often for these purposes is based on the use of reference materials. The proper use of these materials means that laboratory results may be traced to the International System of Units, analytical methodologies can be validated, instruments calibrated and chemical measurements harmonized. One of the biggest challenges in developing reference materials is that of certifying their properties, a process that has been defined as assigning a concentration value that is as close as possible to the true value together with its uncertainty. Organizations that produce reference materials use several options for their certification process, and among these is the use of a primary method. Among the primary methods recognized by the International Office of Weights and Measures is the Isotope Dilution Mass Spectrometry technique. The Chilean Nuclear Energy Commission, through its Reference Materials Program, has prepared a reference material of clam tissue, which has been chemically defined by different analytical methodologies applied in different national and international laboratories. This work describes the methodology developed with the CIEMAT for determining the elements lead, cadmium and zinc in the clam tissue reference material using the primary technique of Isotope Dilution Mass Spectrometry. The calculation is described for obtaining the spike amounts to be added to the sample and the procedure is explained for carrying out the isotopic exchange. The isotopic relationships 204 Pb/ 205 Pb, 111 Cd/ 114 Cd and 66 Zn/ 67 Zn were determined in an atomic emission spectrometer with a plasma source with the following characteristics: plasma

Automated gravimetric sample pretreatment using an industrial robot for the high-precision determination of plutonium by isotope dilution mass spectrometry

International Nuclear Information System (INIS)

Surugaya, Naoki; Hiyama, Toshiaki; Watahiki, Masaru

2008-01-01

A robotized sample-preparation method for the determination of Pu, which is recovered by extraction reprocessing of spent nuclear fuel, by isotope dilution mass spectrometry (IDMS) is described. The automated system uses a six-axis industrial robot, whose motility is very fast, accurate, and flexible, installed in a glove box. The automation of the weighing and dilution steps enables operator-unattended sample pretreatment for the high-precision analysis of Pu in aqueous solutions. Using the developed system, the Pu concentration in a HNO 3 medium was successfully determined using a set of subsequent mass spectrometric measurements. The relative uncertainty in determining the Pu concentration by IDMS using this system was estimated to be less than 0.1% (k=2), which is equal to that expected of a talented analysis. The operation time required was the same as that for a skilled operator. (author)

Continuous-flow isotope ratio mass spectrometry method for carbon and hydrogen isotope measurements on atmospheric methane

Directory of Open Access Journals (Sweden)

M. Brass

2010-12-01

Full Text Available We describe a continuous-flow isotope ratio mass spectrometry (CF-IRMS technique for high-precision δD and δ¹³C measurements of atmospheric methane on 40 mL air samples. CH₄ is separated from other air components by utilizing purely physical processes based on temperature, time and mechanical valve switching. Chemical agents are avoided. Trace amounts of interfering compounds can be separated by gas chromatography after pre-concentration of the CH₄ sample. The purified sample is then either combusted to CO₂ or pyrolyzed to H₂ for stable isotope measurement. Apart from connecting samples and refilling liquid nitrogen as coolant the system is fully automated and allows an unobserved, continuous analysis of samples. The analytical system has been used for analysis of air samples with CH₄ mixing ratios between ~100 and ~10 000 ppb, for higher mixing ratios samples usually have to be diluted.

Isotopic separation by ion chromatography

International Nuclear Information System (INIS)

Albert, M.G.; Barre, Y.; Neige, R.

1994-01-01

The isotopic exchange reaction and the isotopic separation factor are first recalled; the principles of ion chromatography applied to lithium isotope separation are then reviewed (displacement chromatography) and the process is modelled in the view of dimensioning and optimizing the industrial process; the various dimensioning parameters are the isotopic separation factor, the isotopic exchange kinetics and the material flow rate. Effects of the resin type and structure are presented. Dimensioning is also affected by physico-chemical and hydraulic parameters. Industrial implementation features are also discussed. 1 fig., 1 tab., 5 refs

Quantitative analysis of 39 polybrominated diphenyl ethers by isotope dilution GC/low-resolution MS.

Science.gov (United States)

Ackerman, Luke K; Wilson, Glenn R; Simonich, Staci L

2005-04-01

A GC/low-resolution MS method for the quantitative isotope dilution analysis of 39 mono- to heptabrominated diphenyl ethers was developed. The effects of two different ionization sources, electron impact (EI) and electron capture negative ionization (ECNI), and the effects of their parameters on production of high-mass fragment ions [M - xH - yBr](-) specific to PBDEs were investigated. Electron energy, emission current, source temperature, ECNI system pressure, and choice of ECNI reagent gases were optimized. Previously unidentified enhancement of PBDE high-mass fragment ion [M - xH - yBr](-) abundance was achieved. Electron energy had the largest impact on PBDE high-mass fragment ion abundance for both the ECNI and EI sources. By monitoring high-mass fragment ions of PBDEs under optimized ECNI source conditions, quantitative isotope dilution analysis of 39 PBDEs was conducted using nine (13)C(12) labeled PBDEs on a low-resolution MS with low picogram to femtogram instrument detection limits.

The separation and determination of fatty acids by isotopic dilution and radiogas-liquid chromatography

International Nuclear Information System (INIS)

Beardsley, D.A.

1981-01-01

A number of static phases have been evaluated for the GLC separation of fatty acids. Of those investigated, only AT 1200 was capable of resolving the isomeric forms of the acids. A radiogas-liquid chromatographic method incorporating isotopic dilution analysis has been developed for the determination of n-butyric acid. The proposed method has been applied to the determination of the acid in hydrolysed butter fat and milk chocolate extracts. (author)

Determination of mercury in coal by isotope dilution cold-vapor generation inductively coupled plasma mass spectrometry

Energy Technology Data Exchange (ETDEWEB)

Long, S.E.; Kelly, W.R.

2002-04-01

A method based on isotope dilution cold-vapor inductively coupled plasma mass spectrometry (ID-CV-ICPMS) has been developed for high-accuracy determinations of mercury in bituminous and sub-bituminous coals. A closed-system digestion process employing a Carius tube is used to completely oxidize the coal matrix and chemically equilibrate the mercury in the sample with a Hg-201 isotopic spike. The digestates are diluted with high-purity quartz-distilled water, and the mercury is released as a vapor by reduction with tin chloride. Measurements of Hg-201/Hg-202 isotope ratios are made using a quadrupole ICPMS system in time-resolved analysis mode. The new method has some significant advantages over existing methods. The instrument detection limit is less than 1 pg/mL. The average blank (n = 17) is 30 pg, which is roughly 1 order of magnitude lower than the equivalent microwave digestion procedure. The detection limit in coal is blank limited and is similar to 40 pg/g. Memory effects are very low. The relative reproducibility of the analytical measurements is similar to 0.5% for mercury concentrations in the range 10-150 ng/g. The method has been used to measure mercury concentrations in six coal reference materials, SRM 1632b (77.4 ng/g), SRM 1632c (94.3 ng/g), BCR 40 (433.2 ng/g), BCR 180 (125.0 ng/g), BCR 181 (135.8 ng/g), and SARM 20 (252.6 ng/g), as well as a coal fly ash, SRM 1633b (143.1 ng/g). The method is equally applicable to other types of fossil fuels including both crude and refined oils.

Reduction of measurement uncertainty by experimental design in high-order (double, triple, and quadruple) isotope dilution mass spectrometry: application to GC-MS measurement of bromide.

Science.gov (United States)

Pagliano, Enea; Mester, Zoltán; Meija, Juris

2013-03-01

Since its introduction a century ago, isotope dilution analysis has played a central role in developments of analytical chemistry. This method has witnessed many elaborations and developments over the years. To date, we have single, double, and even triple isotope dilution methods. In this manuscript, we summarize the conceptual aspects of isotope dilution methods and introduce the quadruple dilution and the concept of exact matching triple and quadruple dilutions. The comparison of isotope dilution methods is performed by determination of bromide ions in groundwater using novel ethyl-derivatization chemistry in conjunction with GC/MS. We show that the benefits of higher-order isotope dilution methods are countered with a greater need for careful experimental design of the isotopic blends. Just as for ID(2)MS, ID(3)MS and ID(4)MS perform best when the isotope ratio of one sample/spike blend is matched with that of a standard/spike blend (exact matching).

Determination of sulfur in steels by isotope dilution mass spectrometry after dissolution with sealed tube

International Nuclear Information System (INIS)

Watanabe, Kazuo

1981-01-01

The scaled tube dissolution technique was studied for the complete conversion of sulfur in steels to sulfate. Isotope dilution mass spectrometry was used for the determination of sulfur in the sulfate. Sample (0.5 g) was dissolved in nitric acid (7 ml) and hydrochloric acid (3 ml) in a scaled borosilicate glass tube on being heated above 180 0 C overnight. Nitrate ions were removed by repeated evaporation with hydrochloric acid. The residue was dissolved in hydrochloric acid. Sulfate was reduced with a mixture of hydrochloric, hydroiodic and hypophosphorous acids; hydrogen sulfide evolved was absorbed in cadmium acetate solution, then converted to silver sulfide, which was burned to sulfur dioxide in pure oxygen at low pressure, for isotopic analysis. Analytical blank in whole procedure was 0.8 μg of sulfur. This technique was applied to the determination of sulfur in NBS low alloy steels. The principal cause of low values obtained by the open beaker dissolution technique was evaporation losses of sulfur as sulfur dioxide during the dissolution. (author)

Acetone and acetaldehyde determination in tomato juice by isotopic dilution

International Nuclear Information System (INIS)

Piva, M.-T.; Crouzet, J.

1977-01-01

Acetone and acetaldehyde content of tomato juice were determined by isotope dilution techniques. The juice is added to 14 C labelled compounds, carried along by nitrogen at low pressure. The mixture of 2.4 dinitrophenylhydrazones obtained from volatile compounds is separated by thin layer chromatography on silica gel and then on alumina. A determination of radioactivity and concentration of acetone and acetaldehyde 2,4 dinitrophenylhydrazones obtained after separation and elution allow to calculate the content of these two compounds in the initial product with the same sample. This technique could be used for determination of methanol and ethanol after transformation in 3,5 dinitrobenzoates [fr

Simultaneous analysis of (13)C-glutathione as its dimeric form GSSG and its precursor [1-(13)C]glycine using liquid chromatography/isotope ratio mass spectrometry

NARCIS (Netherlands)

Schierbeek, Henk; Rook, Denise; te Braake, Frans W. J.; Dorst, Kristien Y.; Voortman, Gardi; Godin, Jean-Philippe; Fay, Laurent-Bernard; van Goudoever, Johannes B.

2009-01-01

Determination of glutathione kinetics using stable isotopes requires accurate measurement of the tracers and tracees. Previously, the precursor and synthesized product were measured with two separate techniques, liquid chromatography/isotope ratio mass spectrometry (LC/IRMS) and gas

Liquid and gas chromatography coupled to isotope ratio mass spectrometry for the determination of 13C-valine isotopic ratios in complex biological samples.

Science.gov (United States)

Godin, Jean-Philippe; Breuillé, Denis; Obled, Christiane; Papet, Isabelle; Schierbeek, Henk; Hopfgartner, Gérard; Fay, Laurent-Bernard

2008-10-01

On-line gas chromatography-combustion-isotope ratio mass spectrometry (GC-C-IRMS) is commonly used to measure isotopic ratios at natural abundance as well as for tracer studies in nutritional and medical research. However, high-precision (13)C isotopic enrichment can also be measured by liquid chromatography-isotope ratio mass spectrometry (LC-IRMS). Indeed, LC-IRMS can be used, as shown by the new method reported here, to obtain a baseline separation and to measure (13)C isotopic enrichment of underivatised amino acids (Asp, Thr-Ser, Glu, Pro, Gly, Ala, Cys and Val). In case of Val, at natural abundance, the SD(delta(13)C) reported with this method was found to be below 1 per thousand . Another key feature of the new LC-IRMS method reported in this paper is the comparison of the LC-IRMS approach with the conventional GC-C-IRMS determination. To perform this comparative study, isotopic enrichments were measured from underivatised Val and its N(O, S)-ethoxycarbonyl ethyl ester derivative. Between 0.0 and 1.0 molar percent excess (MPE) (delta(13)C= -12.3 to 150.8 per thousand), the calculated root-mean-square (rms) of SD was 0.38 and 0.46 per thousand and the calculated rms of accuracy was 0.023 and 0.005 MPE, respectively, for GC-C-IRMS and LC-IRMS. Both systems measured accurately low isotopic enrichments (0.002 atom percent excess (APE)) with an SD (APE) of 0.0004. To correlate the relative (delta(13)C) and absolute (atom%, APE and MPE) isotopic enrichment of Val measured by the GC-C-IRMS and LC-IRMS devices, mathematical equations showing the slope and intercept of the curves were established and validated with experimental data between 0.0 to 2.3 MPE. Finally, both GC-C-IRMS and LC-IRMS instruments were also used to assess isotopic enrichment of protein-bound (13)C-Val in tibial epiphysis in a tracer study performed in rats. Isotopic enrichments measured by LC-IRMS and GC-C-IRMS were not statistically different (p>0.05). The results of this work indicate that

Application of gas chromatography in hydrogen isotope separation

International Nuclear Information System (INIS)

Ye Xiaoqiu; Sang Ge; Peng Lixia; Xue Yan; Cao Wei

2008-01-01

The principle of gas chromatographic separation of hydrogen isotopes was briefly introduced. The main technology and their development of separating hydrogen isotopes, including elution chromatography, hydrogen-displacement chromatography, self-displacement chromatography and frontal chromatography were discussed in detail. The prospect of hydrogen isotope separation by gas chromatography was presented. (authors)

The use of stable isotopes and gas chromatography/mass spectrometry in the identification of steroid metabolites in the equine

International Nuclear Information System (INIS)

Houghton, E.; Dumasia, M.C.; Teale, P.; Smith, S.J.; Cox, J.; Marshall, D.; Gower, D.B.

1990-01-01

Stable isotope gas chromatography/mass spectrometry has been used successfully in the elucidation of structures of urinary steroid metabolites in the horse and in the identification of metabolites isolated from in vivo perfusion and in vitro incubation studies using equine tissue preparations. Deuterium-labeled steroids, testosterone, dehydroepiandrosterone, and 5-androstene-3 beta,17 beta-diol have been synthesized by base-catalyzed isotope exchange methods and the products characterized by gas chromatography/mass spectrometry. [16,16(-2)H2]Dehydroepiandrosterone (plus radiolabeled dehydroepiandrosterone) was perfused into a testicular artery of a pony stallion and was shown to be metabolized into 2H2-labeled testosterone, 4-androstenedione, isomers of 5-androstene-3,17-diol, 19-hydroxytestosterone, and 19-hydroxy-4-androstenedione. In further studies, equine testicular minces have been incubated with 2H2-labeled and radiolabeled dehydroepiandrosterone and 5-androstene-3 beta, 17 beta-diol. The metabolites, whose identity was confirmed by stable isotope gas chromatography/mass spectrometry, proved the interconversion of the two substrates, as well as formation of testosterone and 4-androstenedione. The aromatization of dehydroepiandrosterone was also confirmed, together with the formation of an isomer of 5(10)-estrene-3,17-diol from both substrates showing 19-demethylation without concomitant aromatization. In studies of the feto-placental unit, the allantochorion was shown to aromatize [2H5]testosterone to [2H4]estradiol, the loss of one 2H from the substrate being consistent with aromatization of the A ring. The formation of 6-hydroxyestradiol was also confirmed in this study. The same technique has been valuable in determining the structure of two metabolites of nandrolone isolated from horse urine

Rapid assay of resveratrol in red wine by paper spray tandem mass spectrometry and isotope dilution.

Science.gov (United States)

Di Donna, Leonardo; Taverna, Domenico; Indelicato, Serena; Napoli, Anna; Sindona, Giovanni; Mazzotti, Fabio

2017-08-15

A rapid analytical approach for the assay of resveratrol in red wines, based on Paper Spray Mass Spectrometry (PS-MS) and Multiple Reaction Monitoring (MRM) is described. The assay involves the use of the stable isotope dilution method. The analytical parameters calculated analyzing fortified samples confirm the reliability of the proposed approach, with accuracy values about 100%, and LOD and LOQ values calculated at 0.5 and 0.8μg/mL, respectively. Furthermore, both the recovery, which was quantitative for the analyte, and the reproducibility (RSD%), checked on different days on the same wine, always below 7%, highlighted the consistency of the methodology. Copyright © 2017 Elsevier Ltd. All rights reserved.

Recent development in isotope ratio mass spectrometry

International Nuclear Information System (INIS)

Platzner, I.

1992-01-01

Within the limited of this review the following topics will be briefly discussed: a) Accuracy, precision, internal relative standard deviation (RISD) and external relative standard deviation (RESD) of isotope ratio measurements. With advanced instrumentation and use of standard reference materials, high accuracy and RESD = 0.002% (or better) may be achieved; b) The advantages of modern automatic isotope ratio mass spectrometer are briefly described. Computer controlled operation and data acquisition, and multiple ion collection are the recent important improvement; c) The isotopic fractionation during the course of isotope ratio measurement is considered as a major source of errors in thermal ionization of metallic elements. The phenomenon in strontium, neodymium, uranium, lead and calcium and methods to correct the measured data are discussed; d) Applications of isotope ratio mass spectrometry in atomic weight determinations, the isotope dilution technique, isotope geology, and isotope effects in biological systems are described together with specific applications in various research and technology area. (author)

Stable Chlorine Isotopes and Elemental Chlorine by Thermal Ionization Mass Spectrometry and Ion Chromatography; Martian Meteorites, Carbonaceous Chondrites and Standard Rocks

Science.gov (United States)

Nakamura, N.; Nyquist, L. E.; Reese, Y.; Shih, C.-Y.; Fujitani, T.; Okano, O.

2011-01-01

Recently significantly large mass fractionation of stable chlorine isotopes has been reported for terrestrial and lunar samples [1,2]. In addition, in view of possible early solar system processes [3] and also potential perchlorate-related fluid/microbial activities on the Martian surface [4,5], a large chlorine isotopic fractionation might be expected for some types of planetary materials. Due to analytical difficulties of isotopic and elemental analyses, however, current chlorine analyses for planetary materials are controversial among different laboratories, particularly between IRMS (gas source mass spectrometry) and TIMS (Thermal Ionization Mass Spectrometry) groups [i.e. 1,6,7] for isotopic analyses, as well as between those doing pyrohydrolysis and other groups [i.e. 6,8]. Additional careful investigations of Cl isotope and elemental abundances are required to confirm real chlorine isotope and elemental variations for planetary materials. We have developed a TIMS technique combined with HF-leaching/ion chromatography at NASA JSC that is applicable to analysis of small amounts of meteoritic and planetary materials. We present here results for several standard rocks and meteorites, including Martian meteorites.

Direct determination of mercury in cosmetic samples by isotope dilution inductively coupled plasma mass spectrometry after dissolution with formic acid

Energy Technology Data Exchange (ETDEWEB)

Gao, Ying; Shi, Zeming; Zong, Qinxia; Wu, Peng; Su, Jing [Sichuan Provincial Key Laboratory of Nuclear Technology in Geology, College of Nuclear Technology and Automation Engineering, Chengdu University of Technology, Chengdu 610059 (China); Liu, Rui, E-mail: liur.ray@gmail.com [Mineral Resources Chemistry Key Laboratory of Sichuan Higher Education Institutions, College of Materials and Chemistry and Chemical Engineering, Chengdu University of Technology, Chengdu 610059 (China)

2014-02-17

Graphical abstract: -- Highlights: •Simple, sensitive, and accurate method is established for mercury determination in cosmetics. •The sample preparation procedure is highly simplified. •Isotope dilution efficiently eliminates matrix effect. •First report of using formic acid based method in combination with PVG-ID-ICP MS for mercury quantitation in cosmetics. -- Abstract: A new method was proposed for the accurate determination of mercury in cosmetic samples based on isotopic dilution (ID)-photochemical vapor generation (PVG)-inductively coupled plasma mass spectrometry (ICP MS) measurement. Cosmetic samples were directly dissolved in formic acid solution and subsequently subjected to PVG for the reduction of mercury into vapor species following by ICP MS detection. Therefore, the risks of analyte contamination and loss were avoided. Highly enriched {sup 201}Hg isotopic spike is added to cosmetics and the isotope ratios of {sup 201}Hg/{sup 202}Hg were measured for the quantitation of mercury. With ID calibration, the influences originating from sample matrixes for the determination of mercury in cosmetic samples have been efficiently eliminated. The effects of several experimental parameters, such as the concentration of the formic acid, and the flow rates of carrier gas and sample were investigated. The method provided good reproducibility and the detection limits were found to be 0.6 pg mL{sup −1}. Finally, the developed method was successfully applied for the determination of mercury in six cosmetic samples and a spike test was performed to verify the accuracy of the method.

On-line double isotope dilution laser ablation inductively coupled plasma mass spectrometry for the quantitative analysis of solid materials.

Science.gov (United States)

Fernández, Beatriz; Rodríguez-González, Pablo; García Alonso, J Ignacio; Malherbe, Julien; García-Fonseca, Sergio; Pereiro, Rosario; Sanz-Medel, Alfredo

2014-12-03

We report on the determination of trace elements in solid samples by the combination of on-line double isotope dilution and laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS). The proposed method requires the sequential analysis of the sample and a certified natural abundance standard by on-line IDMS using the same isotopically-enriched spike solution. In this way, the mass fraction of the analyte in the sample can be directly referred to the certified standard so the previous characterization of the spike solution is not required. To validate the procedure, Sr, Rb and Pb were determined in certified reference materials with different matrices, including silicate glasses (SRM 610, 612 and 614) and powdered samples (PACS-2, SRM 2710a, SRM 1944, SRM 2702 and SRM 2780). The analysis of powdered samples was carried out both by the preparation of pressed pellets and by lithium borate fusion. Experimental results for the analysis of powdered samples were in agreement with the certified values for all materials. Relative standard deviations in the range of 6-21% for pressed pellets and 3-21% for fused solids were obtained from n=3 independent measurements. Minimal sample preparation, data treatment and consumption of the isotopically-enriched isotopes are the main advantages of the method over previously reported approaches. Copyright © 2014 Elsevier B.V. All rights reserved.

The measurement of the isotope ratios and concentrations of zinc by thermal ionization mass spectrometry using double isotope dilution

International Nuclear Information System (INIS)

Deng Zhongguo

1994-01-01

The isotope ratios and concentrations of zinc are measured by silicagel-thermal ionization mass spectrometry using the double isotope spikers. The double isotope spikers ( 70 Zn and 67 Zn-enriched isotopes) are used to correct the isotope mass fractionation for the zinc isotope ratios, and to certify the zinc concentrations in the unknown samples. The zinc concentrations of these double isotope spikers are surveyed by a spiker made of pure (99.99%) natural zinc metal powder. The correcting factors (f a , f t and f n ) of the zinc isotope ratios in the spiked mixture, spike and unspiked samples for the isotope mass fractionation, and the spike-to-unspiked ratios (X r ) of the zinc isotope r in the spiked mixture samples can be obtained to solve the matrix equations by numerical approximation. The natural zinc isotope ratios are: 64 Zn/ 67 Zn = 11.8498, 66 Zn/ 67 Zn = 6.7977, 68 Zn/ 67 Zn = 4.5730 and 70 Zn/ 67 Zn = 0.1520. The uncertainties determined of the isotope ratios and concentrations of zinc are +- 0.16% and +-0.31%, respectively

Development of isotope dilution gamma-ray spectrometry for plutonium analysis

Energy Technology Data Exchange (ETDEWEB)

Li, T.K.; Parker, J.L. (Los Alamos National Lab., NM (United States)); Kuno, Y.; Sato, S.; Kurosawa, A.; Akiyama, T. (Power Reactor and Nuclear Fuel Development Corp., Tokai, Ibaraki (Japan))

1991-01-01

We are studying the feasibility of determining the plutonium concentration and isotopic distribution of highly radioactive, spent-fuel dissolver solutions by employing high-resolution gamma-ray spectrometry. The study involves gamma-ray plutonium isotopic analysis for both dissolver and spiked dissolver solution samples, after plutonium is eluted through an ion-exchange column and absorbed in a small resin bead bag. The spike is well characterized, dry plutonium containing {approximately}98% of {sup 239}Pu. By using measured isotopic information, the concentration of elemental plutonium in the dissolver solution can be determined. Both the plutonium concentration and the isotopic composition of the dissolver solution obtained from this study agree well with values obtained by traditional isotope dilution mass spectrometry (IDMS). Because it is rapid, easy to operate and maintain, and costs less, this new technique could be an alternative method to IDMS for input accountability and verification measurements in reprocessing plants. 7 refs., 4 figs., 4 tabs.

Determination of serum calcium levels by 42Ca isotope dilution inductively coupled plasma mass spectrometry.

Science.gov (United States)

Han, Bingqing; Ge, Menglei; Zhao, Haijian; Yan, Ying; Zeng, Jie; Zhang, Tianjiao; Zhou, Weiyan; Zhang, Jiangtao; Wang, Jing; Zhang, Chuanbao

2017-11-27

Serum calcium level is an important clinical index that reflects pathophysiological states. However, detection accuracy in laboratory tests is not ideal; as such, a high accuracy method is needed. We developed a reference method for measuring serum calcium levels by isotope dilution inductively coupled plasma mass spectrometry (ID ICP-MS), using 42Ca as the enriched isotope. Serum was digested with 69% ultrapure nitric acid and diluted to a suitable concentration. The 44Ca/42Ca ratio was detected in H2 mode; spike concentration was calibrated by reverse IDMS using standard reference material (SRM) 3109a, and sample concentration was measured by a bracketing procedure. We compared the performance of ID ICP-MS with those of three other reference methods in China using the same serum and aqueous samples. The relative expanded uncertainty of the sample concentration was 0.414% (k=2). The range of repeatability (within-run imprecision), intermediate imprecision (between-run imprecision), and intra-laboratory imprecision were 0.12%-0.19%, 0.07%-0.09%, and 0.16%-0.17%, respectively, for two of the serum samples. SRM909bI, SRM909bII, SRM909c, and GBW09152 were found to be within the certified value interval, with mean relative bias values of 0.29%, -0.02%, 0.10%, and -0.19%, respectively. The range of recovery was 99.87%-100.37%. Results obtained by ID ICP-MS showed a better accuracy than and were highly correlated with those of other reference methods. ID ICP-MS is a simple and accurate candidate reference method for serum calcium measurement and can be used to establish and improve serum calcium reference system in China.

Determination of fission products and actinides by inductively coupled plasma-mass spectrometry using isotope dilution analysis. A study of random and systematic errors

International Nuclear Information System (INIS)

Ignacio Garcia Alonso, Jose

1995-01-01

The theory of the propagation of errors (random and systematic) for isotope dilution analysis (IDA) has been applied to the analysis of fission products and actinide elements by inductively coupled plasma-mass spectrometry (ICP-MS). Systematic errors in ID-ICP-MS arising from mass-discrimination (mass bias), detector non-linearity and isobaric interferences in the measured isotopes have to be corrected for in order to achieve accurate results. The mass bias factor and the detector dead-time can be determined by using natural elements with well-defined isotope abundances. A combined method for the simultaneous determination of both factors is proposed. On the other hand, isobaric interferences for some fission products and actinides cannot be eliminated using mathematical corrections (due to the unknown isotope abundances in the sample) and a chemical separation is necessary. The theory for random error propagation in IDA has been applied to the determination of non-natural elements by ICP-MS taking into account all possible sources of uncertainty with pulse counting detection. For the analysis of fission products, the selection of the right spike isotope composition and spike to sample ratio can be performed by applying conventional random propagation theory. However, it has been observed that, in the experimental determination of the isotope abundances of the fission product elements to be determined, the correction for mass-discrimination and the correction for detector dead-time losses contribute to the total random uncertainty. For the instrument used in the experimental part of this study, it was found that the random uncertainty on the measured isotope ratios followed Poisson statistics for low counting rates whereas, for high counting rates, source instability was the main source of error

An isotope-dilution standard GC/MS/MS method for steroid hormones in water

Science.gov (United States)

Foreman, William T.; Gray, James L.; ReVello, Rhiannon C.; Lindley, Chris E.; Losche, Scott A.

2013-01-01

An isotope-dilution quantification method was developed for 20 natural and synthetic steroid hormones and additional compounds in filtered and unfiltered water. Deuterium- or carbon-13-labeled isotope-dilution standards (IDSs) are added to the water sample, which is passed through an octadecylsilyl solid-phase extraction (SPE) disk. Following extract cleanup using Florisil SPE, method compounds are converted to trimethylsilyl derivatives and analyzed by gas chromatography with tandem mass spectrometry. Validation matrices included reagent water, wastewater-affected surface water, and primary (no biological treatment) and secondary wastewater effluent. Overall method recovery for all analytes in these matrices averaged 100%; with overall relative standard deviation of 28%. Mean recoveries of the 20 individual analytes for spiked reagent-water samples prepared along with field samples analyzed in 2009–2010 ranged from 84–104%, with relative standard deviations of 6–36%. Detection levels estimated using ASTM International’s D6091–07 procedure range from 0.4 to 4 ng/L for 17 analytes. Higher censoring levels of 100 ng/L for bisphenol A and 200 ng/L for cholesterol and 3-beta-coprostanol are used to prevent bias and false positives associated with the presence of these analytes in blanks. Absolute method recoveries of the IDSs provide sample-specific performance information and guide data reporting. Careful selection of labeled compounds for use as IDSs is important because both inexact IDS-analyte matches and deuterium label loss affect an IDS’s ability to emulate analyte performance. Six IDS compounds initially tested and applied in this method exhibited deuterium loss and are not used in the final method.

Development of a mass spectrometrical isotope dilution analysis for determination of trace iodine levels and its application for food samples

International Nuclear Information System (INIS)

Schindlmeier, W.

1984-01-01

A mass spectrometrical isotope dilution procedure for the determination of trace amounts of iodine in various materials was developed using 129 I as indicator isotope, based on the determination of the 129 I/ 127 I isotope relationship. Negative thermionization was used as ionization method. The analysis procedure, which worked with a standard deviation of between 0,1 and 10% (depending on material tested), was used to determine the iodine level of table salt - both iodized and normal salt (3-6 ppm and less than 0,006 ppm respectively), and food samples with an organic matrix. For comparison the iodine levels were also measured with an iodine-selective electrode. Special preparation and separation procedures were done to suit the sample material. A comparison of the levels of iodine concentration in various powdered milks which were measured by international collaborators using varying methods shows the superior reproducibility of the MS-IDA. (RB) [de

Isotope dilution ICP-MS with laser-assisted sample introduction for direct determination of sulfur in petroleum products.

Science.gov (United States)

Boulyga, Sergei F; Heilmann, Jens; Heumann, Klaus G

2005-08-01

Inductively coupled plasma isotope dilution mass spectrometry (ICP-IDMS) with direct laser-assisted introduction of isotope-diluted samples into the plasma, using a laser ablation system with high ablation rates, was developed for accurate sulfur determinations in different petroleum products such as 'sulfur-free' premium gasoline, diesel fuel, and heating oil. Two certified gas oil reference materials were analyzed for method validation. Two different 34S-enriched spike compounds, namely, elementary sulfur dissolved in xylene and dibenzothiophene in hexane, were synthesized and tested for their usefulness in this isotope dilution technique. The isotope-diluted sample was adsorbed on a filter-paper-like material, which was fixed in a special holder for irradiation by the laser beam. Under these conditions no time-dependent spike/analyte fractionation was only observed for the dibenzothiophene spike during the laser ablation process, which means that the measured 34S/32S isotope ratio of the isotope-diluted sample remained constant-a necessary precondition for accurate results with the isotope dilution technique. A comparison of LA-ICP-IDMS results with the certified values of the gas oil reference materials and with results obtained from ICP-IDMS analyses with wet sample digestion demonstrated the accuracy of the new LA-ICP-IDMS method in the concentration range of 9.2 microg g(-1) ('sulfur-free' premium gasoline) to 10.4 mg g(-1) (gas oil reference material BCR 107). The detection limit for sulfur by LA-ICP-IDMS is 0.04 microg g(-1) and the analysis time is only about 10 min, which therefore also qualifies this method for accurate determinations of low sulfur contents in petroleum products on a routine level.

Determination of iodine in oyster tissue by isotope dilution laser resonance ionization mass spectrometry

International Nuclear Information System (INIS)

Fassett, J.D.; Murphy, T.J.

1990-01-01

The technique of laser resonance ionization mass spectrometry has been combined with isotope dilution analysis to determine iodine in oyster tissue. The long-lived radioisotope, 129I, was used to spike the samples. Samples were equilibrated with the 129I, wet ashed under controlled conditions, and iodine separated by coprecipitation with silver chloride. The analyte was dried as silver ammonium iodide upon a tantalum filament from which iodine was thermally desorbed in the resonance ionization mass spectrometry instrument. A single-color, two-photon resonant plus one-photon ionization scheme was used to form positive iodine ions. Long-lived iodine signals were achieved from 100 ng of iodine. The precision of 127I/129I measurement has been evaluated by replicate determinations of the spike, the spike calibration samples, and the oyster tissue samples and was 1.0%. Measurement precision among samples was 1.9% for the spike calibration and 1.4% for the oyster tissue. The concentration of iodine determined in SRM 1566a, Oyster Tissue, was 4.44 micrograms/g with an estimate of the overall uncertainty for the analysis of +/- 0.12 microgram/g

A new method for the determination of NO2 traces using isotope dilution and mass spectrometry analysis

International Nuclear Information System (INIS)

Stevens, C.; Barat, F.; Nguyen Nghi, H.

1975-01-01

A new method for the determination of NO 2 traces, in the order of 1ppb (10 -9 ), in atmosphere and stratosphere is described. The method consists in an isotope dilution technique using 15 NO 2 , followed by the reduction of NO 2 to N 2 and a mass spectrometry analysis. A known amount of 15 NO 2 is added to the air samples. Then, NO 2 is separated from H 2 O, HNO 3 , CO 2 and N 2 O and transferred to a SiO 2 reactor by trapping at -196 deg C. In the reactor NO 2 is reduced to N 2 by reaction with electrolytic Cu heated at 580 deg C. The mass 29/mass 30 ratio corresponding to 15 N 14 N and 15 N 15 N is determined by mass spectrometry. The sensitivity of the method depends on the contamination introduced during the analysis of the sample (reagents, separation and measuring devices). The contamination is reproducible and in the order of 4.5+-0.5 10 -2 mm 3 N 2 [fr

Radiogas chromatography mass spectrometry in the selected ion monitoring mode

International Nuclear Information System (INIS)

Doerfler, D.L.; Rosenblum, E.R.; Malloy, J.M.; Naworal, J.D.; McManus, I.R.; Campbell, I.M.

1980-01-01

The value of selected ion monitoring in analyzing biological radio isotope incorporation experiments by radiogas chromatography mass spectrometry is illustrated with reference to the biosynthesis of the mycotoxin mycophenolic acid in Penicillium brevicompactum and the mode of action of the anticholesterolemic drug 20,25-diazacholesterol. Both examples used 1-[ 14 C]acetate precursors. It is shown that the increased sensitivity and specificity of the selected ion monitoring mode detector permits straightforward detection and identification of the relatively small cellular pools associated with metabolic intermediates. The computer program RADSIM is described. Problems that still exist in using radiogas gas chromatography mass spectrometry technology to analyse isotope incorporation experiments are discussed. (author)

Mass spectrometry in clinical chemistry

International Nuclear Information System (INIS)

Pettersen, J.E.

1977-01-01

A brief description is given of the functional elements of a mass spectrometer and of some currently employed mass spectrometric techniques, such as combined gas chromatography-mass spectrometry, mass chromatography, and selected ion monitoring. Various areas of application of mass spectrometry in clinical chemistry are discussed, such as inborn errors of metabolism and other metabolic disorders, intoxications, quantitative determinations of drugs, hormones, gases, and trace elements, and the use of isotope dilution mass spectrometry as a definitive method for the establishment of true values for concentrations of various compounds in reference sera. It is concluded that mass spectrometry is of great value in clinical chemistry. (Auth.)

Quantitation of 5-Methyltetrahydrofolate in Cerebrospinal Fluid Using Liquid Chromatography-Electrospray Tandem Mass Spectrometry.

Science.gov (United States)

Arning, Erland; Bottiglieri, Teodoro

2016-01-01

We describe a simple stable isotope dilution method for accurate and precise measurement of cerebrospinal fluid (CSF) 5-methyltetrahydrofolate (5-MTHF) as a clinical diagnostic test. 5-MTHF is the main biologically active form of folic acid and is involved in regulation of homocysteine and DNA synthesis. Measurement of 5-MTHF in CSF provides diagnostic information regarding diseases affecting folate metabolism within the central nervous system, in particular inborn errors of folate metabolism. Determination of 5-MTHF in CSF (50 μL) was performed utilizing high performance liquid chromatography coupled with electrospray positive ionization tandem mass spectrometry (HPLC-ESI-MS/MS). 5-MTHF in CSF is determined by a 1:2 dilution with internal standard (5-MTHF-(13)C5) and injected directly onto the HPLC-ESI-MS/MS system. Each assay is quantified using a five-point standard curve (25-400 nM) and has an analytical measurement range of 3-1000 nM.

Isotope dilution ICP-MS with laser-assisted sample introduction for direct determination of sulfur in petroleum products

Energy Technology Data Exchange (ETDEWEB)

Boulyga, Sergei F.; Heilmann, Jens; Heumann, Klaus G. [Johannes Gutenberg-University Mainz (Germany). Institute of Inorganic Chemistry and Analytical Chemistry

2005-08-01

Inductively coupled plasma isotope dilution mass spectrometry (ICP-IDMS) with direct laser-assisted introduction of isotope-diluted samples into the plasma, using a laser ablation system with high ablation rates, was developed for accurate sulfur determinations in different petroleum products such as 'sulfur-free' premium gasoline, diesel fuel, and heating oil. Two certified gas oil reference materials were analyzed for method validation. Two different {sup 34}S-enriched spike compounds, namely, elementary sulfur dissolved in xylene and dibenzothiophene in hexane, were synthesized and tested for their usefulness in this isotope dilution technique. The isotope-diluted sample was adsorbed on a filter-paper-like material, which was fixed in a special holder for irradiation by the laser beam. Under these conditions no time-dependent spike/analyte fractionation was only observed for the dibenzothiophene spike during the laser ablation process, which means that the measured {sup 34}S/{sup 32}S isotope ratio of the isotope-diluted sample remained constant - a necessary precondition for accurate results with the isotope dilution technique. A comparison of LA-ICP-IDMS results with the certified values of the gas oil reference materials and with results obtained from ICP-IDMS analyses with wet sample digestion demonstrated the accuracy of the new LA-ICP-IDMS method in the concentration range of 9.2 {mu}g g{sup -1} ('sulfur-free' premium gasoline) to 10.4 mg g{sup -1} (gas oil reference material BCR 107). The detection limit for sulfur by LA-ICP-IDMS is 0.04 {mu}g g{sup -1} and the analysis time is only about 10 min, which therefore also qualifies this method for accurate determinations of low sulfur contents in petroleum products on a routine level. (orig.)

Quantification of γ-Aminobutyric Acid in Cerebrospinal Fluid Using Liquid Chromatography-Electrospray Tandem Mass Spectrometry.

Science.gov (United States)

Arning, Erland; Bottiglieri, Teodoro

2016-01-01

We describe a simple stable isotope dilution method for accurate and precise measurement of γ-aminobutyric acid (GABA), a major inhibitory neurotransmitter in human cerebrospinal fluid (CSF) as a clinical diagnostic test. Determination of GABA in CSF (50 μL) was performed utilizing high performance liquid chromatography coupled with electrospray positive ionization tandem mass spectrometry (HPLC-ESI-MS/MS). Analysis of free and total GABA requires two individual sample preparations and mass spectrometry analyses. Free GABA in CSF is determined by a 1:2 dilution with internal standard (GABA-D2) and injected directly onto the HPLC-ESI-MS/MS system. Determination of total GABA in CSF requires additional sample preparation in order to hydrolyze all the bound GABA in the sample to the free form. This requires hydrolyzing the sample by boiling in acidic conditions (hydrochloric acid) for 4 h. The sample is then further diluted 1:10 with a 90 % acetonitrile/0.1 % formic acid solution and injected into the HPLC-ESI-MS/MS system. Each assay is quantified using a five-point standard curve and is linear from 6 nM to 1000 nM and 0.63 μM to 80 μM for free and total GABA, respectively.

Fast analysis of quaternary ammonium pesticides in food and beverages using cation-exchange chromatography coupled with isotope-dilution high-resolution mass spectrometry.

Science.gov (United States)

Nardin, Tiziana; Barnaba, Chiara; Abballe, Franco; Trenti, Gianmaria; Malacarne, Mario; Larcher, Roberto

2017-10-01

A fast separation based on cation-exchange liquid chromatography coupled with high-resolution mass spectrometry is proposed for simultaneous determination of chlormequat, difenzoquat, diquat, mepiquat and paraquat in several food and beverage commodities. Solid samples were extracted using a mixture of water/methanol/formic acid (69.6:30:0.4, v/v/v), while liquid samples were ten times diluted with the same solution. Separation was carried out on an experimental length-modified IonPac CS17 column (2 × 15 mm 2 ) that allowed the use of formic acid and acetonitrile as mobile phase. Detection limits for food and beverage matrices were established at 1.5 μg/L for chlormequat, difenzoquat and mepiquat, and 3 μg/L for diquat and paraquat, while for drinking water a pre-analytical sample concentration allowed detection limits of 9 and 20 ng/L, respectively. Precision, as repeatability (RSD%), ranged from 0.2 to 24%, with a median value of 6%, and trueness, as recovery, ranged from 64 to 118%, with a median value of 96%. The method developed was successfully applied to investigate the presence of herbicide residues in commercial commodities (mineral water, orange juice, beer, tea, green coffee bean, toasted coffee powder, cocoa bean, white corn flour, rice and sugar samples). © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Direct determination of the samarium:neodymium ratio in geological materials by inductively coupled plasma quadrupole mass spectrometry with cryogenic desolvation. Comparison with isotope dilution thermal ionization mass spectrometry

International Nuclear Information System (INIS)

Pin, Christian; Telouk, Philippe; Imbert, J.-L.

1995-01-01

A cryogenic desolvation unit in the sample introduction system reduces differences in oxide formation between Sm and Nd to very low levels, enabling the direct, standardless determination of their ratio in bulk solutions by inductively coupled plasma mass spectrometry. The measured values are in reasonably good agreement with those determined by the isotope dilution thermal ionization mass spectrometry (ID-TIMS) reference technique. Although this method cannot, at present, compete with ID-TIMS in terms of precision and accuracy, it is much more straightforward and can be used in geochemistry for studies involving the screening of a large number of samples. (author)

Calculation and mitigation of isotopic interferences in liquid chromatography-mass spectrometry/mass spectrometry assays and its application in supporting microdose absolute bioavailability studies.

Science.gov (United States)

Gu, Huidong; Wang, Jian; Aubry, Anne-Françoise; Jiang, Hao; Zeng, Jianing; Easter, John; Wang, Jun-sheng; Dockens, Randy; Bifano, Marc; Burrell, Richard; Arnold, Mark E

2012-06-05

A methodology for the accurate calculation and mitigation of isotopic interferences in liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS) assays and its application in supporting microdose absolute bioavailability studies are reported for the first time. For simplicity, this calculation methodology and the strategy to minimize the isotopic interference are demonstrated using a simple molecule entity, then applied to actual development drugs. The exact isotopic interferences calculated with this methodology were often much less than the traditionally used, overestimated isotopic interferences simply based on the molecular isotope abundance. One application of the methodology is the selection of a stable isotopically labeled internal standard (SIL-IS) for an LC-MS/MS bioanalytical assay. The second application is the selection of an SIL analogue for use in intravenous (i.v.) microdosing for the determination of absolute bioavailability. In the case of microdosing, the traditional approach of calculating isotopic interferences can result in selecting a labeling scheme that overlabels the i.v.-dosed drug or leads to incorrect conclusions on the feasibility of using an SIL drug and analysis by LC-MS/MS. The methodology presented here can guide the synthesis by accurately calculating the isotopic interferences when labeling at different positions, using different selective reaction monitoring (SRM) transitions or adding more labeling positions. This methodology has been successfully applied to the selection of the labeled i.v.-dosed drugs for use in two microdose absolute bioavailability studies, before initiating the chemical synthesis. With this methodology, significant time and cost saving can be achieved in supporting microdose absolute bioavailability studies with stable labeled drugs.

Multi-element determination in environmental samples by mass spectrometric isotope dilution analysis using thermal ionization. Pt. 2

International Nuclear Information System (INIS)

Hilpert, K.; Waidmann, E.

1988-01-01

An analytical procedure for the multi-element analysis of the elements Fe, Ni, Cu, Zn, Ga, Rb, Sr, Cd, Ba, Tl, and Pb in pine needles by mass spectrometric isotope dilution analysis using thermal ionization has been reported in Part I of this paper. This procedure is now transferred to the non-vegetable material 'Oyster Tissue' (Standard Reference Material 1566, National Bureau of Standards, USA). By a modification of the analytical procedure, it was possible to determine Cr in this material in addition to the aforementioned elements. No concentrations are certified for the elements Ga, Ba and Tl analyzed in this work. The concentrations of the remaining elements obtained by the multi-element analysis agree well with those certified. (orig.)

Accurate isotope ratio mass spectrometry. Some problems and possibilities

International Nuclear Information System (INIS)

Bievre, P. de

1978-01-01

The review includes reference to 190 papers, mainly published during the last 10 years. It covers the following: important factors in accurate isotope ratio measurements (precision and accuracy of isotope ratio measurements -exemplified by determinations of 235 U/ 238 U and of other elements including 239 Pu/ 240 Pu; isotope fractionation -exemplified by curves for Rb, U); applications (atomic weights); the Oklo natural nuclear reactor (discovered by UF 6 mass spectrometry at Pierrelatte); nuclear and other constants; isotope ratio measurements in nuclear geology and isotope cosmology - accurate age determination; isotope ratio measurements on very small samples - archaeometry; isotope dilution; miscellaneous applications; and future prospects. (U.K.)

Differential Mobility-Mass Spectrometry Double Spike Isotope Dilution Study of Release of β-Methylaminoalanine and Proteinogenic Amino Acids during Biological Sample Hydrolysis.

Science.gov (United States)

Beach, Daniel G; Kerrin, Elliott S; Giddings, Sabrina D; Quilliam, Michael A; McCarron, Pearse

2018-01-08

The non-protein amino acid β-methylamino-L-alanine (BMAA) has been linked to neurodegenerative disease and reported throughout the environment. Proposed mechanisms of bioaccumulation, trophic transfer and chronic toxicity of BMAA rely on the hypothesis of protein misincorporation. Poorly selective methods for BMAA analysis have led to controversy. Here, a recently reported highly selective method for BMAA quantitation using hydrophilic interaction liquid chromatography-differential mobility spectrometry-tandem mass spectrometry (HILIC-DMS-MS/MS) is expanded to include proteinogenic amino acids from hydrolyzed biological samples. For BMAA quantitation, we present a double spiking isotope dilution approach using D 3 -BMAA and 13 C 15 N 2 -BMAA. These methods were applied to study release of BMAA during acid hydrolysis under a variety of conditions, revealing that the majority of BMAA can be extracted along with only a small proportion of protein. A time course hydrolysis of BMAA from mussel tissue was carried out to assess the recovery of BMAA during sample preparation. The majority of BMAA measured by typical methods was released before a significant proportion of protein was hydrolyzed. Little change was observed in protein hydrolysis beyond typical hydrolysis times but the concentration of BMAA increased linearly. These findings demonstrate protein misincorporation is not the predominant form of BMAA in cycad and shellfish.

Certification measurement of the cadmium, copper and lead contents in rice using isotope dilution inductively coupled plasma mass spectrometry

International Nuclear Information System (INIS)

Vassileva, Emilia; Quetel, Christophe R.

2004-01-01

This paper describes the certification of the Cd, Cu and Pb amount contents in a rice material, that were used as reference values for round 19 of the international measurement evaluation programme (IMEP). The protocol developed in this study was based on isotope dilution associated to inductively coupled plasma mass spectrometry (ID-ICP-MS). A multiple spiking approach was applied to reduce significantly the number of analytical steps. For the decomposition of the sample, three different microwave assisted digestion procedures were tested and compared. The use of hydrofluoric acid was found necessary to ensure full solubilisation and complete isotopic equilibration. Estimation of the combined uncertainty attached to the measurement results was performed according to the ISO guidelines. Contributions from the correction for moisture content, sample homogeneity, procedural blank, spike impurities, spectral interferences, instrumental background and dead-time effects were evaluated. SI-traceable values with less than 2% combined uncertainty (k = 2) were obtained for Cd, Cu and Pb, respectively, (14.39 ± 0.21) x 10 -6 mol kg -1 , (44.31 ± 0.42) x 10 -6 mol kg -1 and (2.034 ± 0.034) x 10 -6 mol kg -1 . The rice powder was observed to be highly hygroscopic and a second series of isotope dilution mass spectrometry measurements was carried out on samples in equilibrium with the ambient moisture conditions ('saturated' samples). The Comite Consultatif pour la Quantite de Matiere (CCQM) requested this approach for the participation to the key comparison 24 on the same rice test material. The excellent agreement for Cd between the IMEP-19 reference value, the value submitted by the institute for reference materials and measurements (IRMM) to CCQM-K24 and the corresponding reference value obtained as the arithmetic mean from the results of the 11 participating National Measurement Institutes (less than 0.27% difference) further validated this work. Eventually, this series

Negative chemical ionization GC/MS determination of nitrite and nitrate in seawater using exact matching double spike isotope dilution and derivatization with triethyloxonium tetrafluoroborate.

Science.gov (United States)

Pagliano, Enea; Meija, Juris; Sturgeon, Ralph E; Mester, Zoltan; D'Ulivo, Alessandro

2012-03-06

The alkylation of nitrite and nitrate by triethyloxonium tetrafluoroborate allows determination of their ethyl esters by headspace gas chromatography/mass spectrometry (GC/MS). In the present study, significant improvement in analytical performance is achieved using negative chemical ionization providing detection limits of 150 ng/L for NO(2)(-) and 600 ng/L for NO(3)(-), an order of magnitude better than those achieved using electron impact ionization. The derivatization procedure was optimized and alkaline conditions adopted to minimize conversion of nitrite to nitrate (determined to be 0.07% at 100 mg/L NO(2)(-)) and to avoid the exchange of oxygen between the analytes and the solvent (water). Quantitation entails use of isotopically enriched standards (N(18)O(2)(-) and (15)NO(3)(-)), which also permits monitoring of potential conversion from nitrite to nitrate during the analysis (double spike isotope dilution).

Online stable carbon isotope ratio measurement in formic acid, acetic acid, methanol and ethanol in water by high performance liquid chromatography-isotope ratio mass spectrometry

International Nuclear Information System (INIS)

Tagami, Keiko; Uchida, Shigeo

2008-01-01

A suitable analysis condition was determined for high performance liquid chromatography-isotope ratio mass spectrometry (HPLC-IRMS) while making sequential measurements of stable carbon isotope ratios of δ 13 C in formic acid, acetic acid, methanol and ethanol dissolved in water. For this online column separation method, organic reagents are not applicable due to carbon contamination; thus, water and KH 2 PO 4 at low concentrations were tested as mobile phase in combination with a HyPURITY AQUASTAR TM column. Formic acid, acetic acid, methanol and ethanol were separated when 2 mM KH 2 PO 4 aqueous solution was used. Under the determined analysis condition for HPLC-IRMS, carbon concentrations could be measured quantitatively as well as carbon isotope ratio when carbon concentration was higher than 0.4 mM L for each chemical

A dilute-and-shoot flow-injection tandem mass spectrometry method for quantification of phenobarbital in urine.

Science.gov (United States)

Alagandula, Ravali; Zhou, Xiang; Guo, Baochuan

2017-01-15

Liquid chromatography/tandem mass spectrometry (LC/MS/MS) is the gold standard of urine drug testing. However, current LC-based methods are time consuming, limiting the throughput of MS-based testing and increasing the cost. This is particularly problematic for quantification of drugs such as phenobarbital, which is often analyzed in a separate run because they must be negatively ionized. This study examined the feasibility of using a dilute-and-shoot flow-injection method without LC separation to quantify drugs with phenobarbital as a model system. Briefly, a urine sample containing phenobarbital was first diluted by 10 times, followed by flow injection of the diluted sample to mass spectrometer. Quantification and detection of phenobarbital were achieved by an electrospray negative ionization MS/MS system operated in the multiple reaction monitoring (MRM) mode with the stable-isotope-labeled drug as internal standard. The dilute-and-shoot flow-injection method developed was linear with a dynamic range of 50-2000 ng/mL of phenobarbital and correlation coefficient > 0.9996. The coefficients of variation and relative errors for intra- and inter-assays at four quality control (QC) levels (50, 125, 445 and 1600 ng/mL) were 3.0% and 5.0%, respectively. The total run time to quantify one sample was 2 min, and the sensitivity and specificity of the method did not deteriorate even after 1200 consecutive injections. Our method can accurately and robustly quantify phenobarbital in urine without LC separation. Because of its 2 min run time, the method can process 720 samples per day. This feasibility study shows that the dilute-and-shoot flow-injection method can be a general way for fast analysis of drugs in urine. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Certification of methylmercury in cod fish tissue certified reference material by species-specific isotope dilution mass spectrometric analysis

Energy Technology Data Exchange (ETDEWEB)

Inagaki, Kazumi; Kuroiwa, Takayoshi; Narukawa, Tomohiro; Yarita, Takashi; Takatsu, Akiko; Okamoto, Kensaku; Chiba, Koichi [National Metrology Institute of Japan (NMIJ), National Institute of Advanced Industrial Science and Technology (AIST), Environmental Standard Section, Tsukuba, Ibaraki (Japan)

2008-07-15

A new cod fish tissue certified reference material, NMIJ CRM 7402-a, for methylmercury analysis was certified by the National Metrological Institute of Japan in the National Institute of Advanced Industrial Science and Technology (NMIJ/AIST). Cod fish was collected from the sea close to Japan. The cod muscle was powdered by freeze-pulverization and was placed into 600 glass bottles (10 g each), which were sterilized with {gamma}-ray irradiation. The certification was carried out using species-specific isotope dilution gas chromatography inductively coupled plasma mass spectrometry (SSID-GC-ICPMS), where {sup 202}Hg-enriched methylmercury (MeHg) was used as the spike compound. In order to avoid any possible analytical biases caused by nonquantitative extraction, degradation and/or formation of MeHg in sample preparations, two different extraction methods (KOH/methanol and HCl/methanol extractions) were performed, and one of these extraction methods utilized two different derivatization methods (ethylation and phenylation). A double ID method was adopted to minimize the uncertainty arising from the analyses. In order to ensure not only the reliability of the analytical results but also traceability to SI units, the standard solution of MeHg used for the reverse-ID was prepared from high-purity MeHg chloride and was carefully assayed as follows: the total mercury was determined by ID-ICPMS following aqua regia digestion, and the ratio of Hg as MeHg to the total Hg content was estimated by GC-ICPMS. The certified value given for MeHg is 0.58 {+-} 0.02 mg kg{sup -1} as Hg. (orig.)

Simultaneous quantification of 21 water soluble vitamin circulating forms in human plasma by liquid chromatography-mass spectrometry.

Science.gov (United States)

Meisser Redeuil, Karine; Longet, Karin; Bénet, Sylvie; Munari, Caroline; Campos-Giménez, Esther

2015-11-27

This manuscript reports a validated analytical approach for the quantification of 21 water soluble vitamins and their main circulating forms in human plasma. Isotope dilution-based sample preparation consisted of protein precipitation using acidic methanol enriched with stable isotope labelled internal standards. Separation was achieved by reversed-phase liquid chromatography and detection performed by tandem mass spectrometry in positive electrospray ionization mode. Instrumental lower limits of detection and quantification reached water soluble vitamins in human plasma single donor samples. The present report provides a sensitive and reliable approach for the quantification of water soluble vitamins and main circulating forms in human plasma. In the future, the application of this analytical approach will give more confidence to provide a comprehensive assessment of water soluble vitamins nutritional status and bioavailability studies in humans. Copyright © 2015 Elsevier B.V. All rights reserved.

Determination of selenite and selenate in human urine by ion chromatography and inductively coupled plasma mass spectrometry

DEFF Research Database (Denmark)

Gammelgaard, Bente; Jons, O.

2000-01-01

The selenium species selenite, selenate and selenomethionine were separated in aqueous solution by ion chromatography. The separation was performed on an IonPac AG11 in series with an AS11 anion exchange column by elution with 25 mM sodium hydroxide in 2% methanol. The Se-78 and Se-82 isotopes were...... monitored in the inductively coupled plasma mass spectrometry (ICP-MS) detector. When the chromatographic system was applied to analysis of urine samples diluted 1 + 1, the selenomethionine signal appeared in the front together with other unresolved selenium species, while the selenite and selenate signals...... and selenate, respectively, corresponding to absolute amounts of 8 and 16 pg, respectively. Calculations were based on peak height measurements of the Se-82 isotope. In 23 analysed urine samples, the concentration of selenite was in the range selenium...

Nutritional assessment by isotope dilution analysis of body composition

International Nuclear Information System (INIS)

Szeluga, D.J.; Stuart, R.K.; Utermohlen, V.; Santos, G.W.

1984-01-01

The three components of body mass, body cell mass (BCM), extracellular fluid (ECF), and fat + extracellular solids (ECS: bone, tendon, etc) can be quantified using established isotope dilution techniques. With these techniques, total body water (TBW) and ECF are measured using 3H 2 O and 82 Bromine, respectively, as tracers. BCM is calculated from intracellular fluid (ICF) where ICF . TBW - ECF. Fat + ECS is estimated as: body weight - (BCM + ECF). TBW and ECF can be determined by either of two calculation methods, one requiring several timed plasma samples (extrapolation method) and one requiring a single plasma sample and a 4-h urine collection (urine-corrected method). The comparability of the two calculation methods was evaluated in 20 studies in 12 bone marrow transplant recipients. We found that for determination of TBW and ECF there was a very strong linear relationship (r2 greater than 0.98) between the calculation methods. Further comparisons (by t test, 2-sided) indicated that for the determination of ECF, the methods were not significantly (p greater than 0.90) different; however, TBW determined by the urine-corrected method was slightly (0.1 to 6%), but significantly (p less than 0.01) greater than that determined by the extrapolation method. Therefore, relative to the extrapolation method, the urine-corrected method ''over-estimates'' BCM and ''under-estimates'' fat + ECS since determination of these compartment sizes depends on measurement of TBW. We currently use serial isotope dilution studies to monitor the body composition changes of patients receiving therapeutic nutritional support

Accuracy of some routine method used in clinical chemistry as judged by isotope dilution-mass spectrometry

International Nuclear Information System (INIS)

Bjoerkhem, I.; Bergman, A.; Falk, O.; Kallner, A.; Lantto, O.; Svensson, L.; Akerloef, E.; Blomstrand, R.

1981-01-01

Serum from patients was pooled, filtered, dispensed, and frozen. This pooled specimen was used for accuracy control in 64 participating laboratories in Sweden. Mean values (state-of-the-art values) were obtained for creatinine, cholesterol, glucose, urea, uric acid, and cortisol. These values were compared with values obtained with highly accurate reference methods based on isotope dilution-mass spectrometry. Differences were marked in the case of determination of creatinine and cortisol. Concerning the other components, the differences between the state-of-the-art value and the values obtained with the reference methods were negligible. Moreover, the glucose oxidase and the oxime methods for determination of glucose and urea were found to give significantly lower values than the hexokinase and urease methods, respectively. Researchers conclude that methods with a higher degree of accuracy are required for routine determination of creatinine and cortisol

Assessment of vitamin A status in rats by isotope dilution: A simplified model

International Nuclear Information System (INIS)

Furr, H.C.; Cooper, D.A.; Olson, J.A.

1990-01-01

Isotope-dilution analysis of vitamin A status requires giving a known quantity of labeled vitamin A to the subject and measuring the ratio of labeled to unlabeled retinol in the blood after a period for equilibration. To calculate total body stores from the isotopic ratio of plasma retinol, several assumptions must be made. In considering new ways of better calculating liver vitamin A stores from isotope-dilution data, the authors used the data of Green et al. to estimate loss of vitamin A tracer as a function of time and of vitamin A status. This correction markedly improves the correlation between calculated and analyzed liver vitamin A stores and also quantitively explains the hyperbolic relationship between fraction of tracer dose recovered in liver and mass of liver vitamin A stores. Agreement of this model with experimental data suggests that efficiency of absorption and storage of vitamin A is not affected by vitamin A status. This model can be used to estimate both the amount of tracer needed for a given lower limit of detection and an optimum sampling time

Isotopic dilution requirements for 233U criticality safety in processing and disposal facilities

International Nuclear Information System (INIS)

Elam, K.R.; Forsberg, C.W.; Hopper, C.M.; Wright, R.Q.

1997-11-01

The disposal of excess 233 U as waste is being considered. Because 233 U is a fissile material, one of the key requirements for processing 233 U to a final waste form and disposing of it is to avoid nuclear criticality. For many processing and disposal options, isotopic dilution is the most feasible and preferred option to avoid nuclear criticality. Isotopic dilution is dilution of fissile 233 U with nonfissile 238 U. The use of isotopic dilution removes any need to control nuclear criticality in process or disposal facilities through geometry or chemical composition. Isotopic dilution allows the use of existing waste management facilities, that are not designed for significant quantities of fissile materials, to be used for processing and disposing of 233 U. The amount of isotopic dilution required to reduce criticality concerns to reasonable levels was determined in this study to be ∼ 0.66 wt% 233 U. The numerical calculations used to define this limit consisted of a homogeneous system of silicon dioxide (SiO 2 ), water (H 2 O), 233 U, and depleted uranium (DU) in which the ratio of each component was varied to determine the conditions of maximum nuclear reactivity. About 188 parts of DU (0.2 wt% 235 U) are required to dilute 1 part of 233 U to this limit in a water-moderated system with no SiO 2 present. Thus, for the US inventory of 233 U, several hundred metric tons of DU would be required for isotopic dilution

Dual element ((15)N/(14)N, (13)C/(12)C) isotope analysis of glyphosate and AMPA by derivatization-gas chromatography isotope ratio mass spectrometry (GC/IRMS) combined with LC/IRMS.

Science.gov (United States)

Mogusu, Emmanuel O; Wolbert, J Benjamin; Kujawinski, Dorothea M; Jochmann, Maik A; Elsner, Martin

2015-07-01

To assess sources and degradation of the herbicide glyphosate [N-(phosphonomethyl) glycine] and its metabolite AMPA (aminomethylphosphonic acid), concentration measurements are often inconclusive and even (13)C/(12)C analysis alone may give limited information. To advance isotope ratio analysis of an additional element, we present compound-specific (15)N/(14)N analysis of glyphosate and AMPA by a two step derivatization in combination with gas chromatography/isotope ratio mass spectrometry (GC/IRMS). The N-H group was derivatized with isopropyl chloroformate (iso-PCF), and remaining acidic groups were subsequently methylated with trimethylsilyldiazomethane (TMSD). Iso-PCF treatment at pH 10 indicated decomposition of the derivative. At pH 10, and with an excess of iso-PCF by 10-24, greatest yields and accurate (15)N/(14)N ratios were obtained (deviation from elemental analyzer-IRMS: -0.2 ± 0.9% for glyphosate; -0.4 ± 0.7% for AMPA). Limits for accurate δ(15)N analysis of glyphosate and AMPA were 150 and 250 ng injected, respectively. A combination of δ(15)N and δ(13)C analysis by liquid chromatography/isotope ratio mass spectrometry (LC/IRMS) (1) enabled an improved distinction of commercial glyphosate products and (2) showed that glyphosate isotope values during degradation by MnO2 clearly fell outside the commercial product range. This highlights the potential of combined carbon and nitrogen isotopes analysis to trace sources and degradation of glyphosate.

Measurements of mass-fraction activity coefficient at infinite dilution of aliphatic and aromatic hydrocarbons, thiophene, alcohols, water, ethers, and ketones in hyperbranched polymer, Boltorn H2004, using inverse gas chromatography

International Nuclear Information System (INIS)

Domanska, Urszula; Zolek-Tryznowska, Zuzanna

2010-01-01

Thermodynamic properties of the hyperbranched polymer, Boltorn H2004 (B-H2004), were investigated by inverse gas chromatography with 42 different solvents: n-alkanes (C 5 -C 10 ), cycloalkanes (C 5 -C 8 ), alkenes (C 5 -C 8 ), alkynes (C 5 -C 8 ), aromatic hydrocarbons (benzene, toluene, ethylbenzene, o-, m-, p-xylene, thiophene), alcohols (C 1 -C 5 ), water, ethers (tetrahydrofuran (THF), methyl-tert-butylether (MTBE), diethyl-, di-n-propyl-, di-n-butyl ether), and ketones (acetone, 2-pentanone, 3-pentanone, 2-hexanone, 3-hexanone, cyclopentanone) at the temperatures from (308.15 to 348.15) K using the inverse gas chromatography (IGC). The density and thermophysical properties of polymer were described. The specific retention volume (V g ), the mass-fraction activity coefficient at infinite dilution (Ω 13 ∞ ), the Flory-Huggins interaction parameter (χ 13 ∞ ), the molar enthalpy of sorption in the polymer (Δ s H), the partial molar excess enthalpy at infinite dilution (ΔH 1 E,∞ ), the molar enthalpy of vaporization to the ideal-gas state for the pure solutes (Δ vap H 0 ), the partial molar Gibbs excess energy at infinite dilution (ΔG 1 E,∞ ), and the solubility parameter of the polymer (δ 3 ), were calculated. The UNIFAC-FV model was used to predict the mass-fraction activity coefficient at infinite dilution for different solutes in the B-H2004 polymer.

Direct determination of halogens in powdered geological and environmental samples using isotope dilution laser ablation ICP-MS

Science.gov (United States)

Boulyga, Sergei F.; Heumann, Klaus G.

2005-04-01

Laser ablation inductively coupled plasma isotope dilution mass spectrometry (LA-ICP-IDMS) with a special laser ablation system for bulk analyses (LINA-Spark(TM)-Atomiser) was applied for direct determinations of chlorine, bromine, and iodine in rock and sediment samples. Special attention was focused on possible inter-halogen fractionations and analyte/spike isotope fractionations by using LA-ICP-MS and LA-ICP-IDMS, respectively. A variation of Br/Cl and I/Cl element intensity ratios by a factor of 1.3-3 was observed when changing the nebulizer gas flow rate in the range of 0.84-1.0 L min-1 and the laser power density in the range of 2-10 GW cm-2, respectively. When using an internal standard for halogen quantification in LA-ICP-MS, this inter-element fractionation can cause systematic errors, which can be avoided by applying the isotope dilution technique. However, at high laser power densities (>5.7 GW cm-2 for iodine and >4.0 GW cm-2 for bromine and chlorine) the corresponding measured isotope ratio of the isotope-diluted sample deviates significantly from the target value. Under optimised conditions concentrations in the range of 30 [mu]g g-1-16 × 103 [mu]g g-1 for chlorine, <2-140 [mu]g g-1 for bromine, and <0.1-31 [mu]g g-1 for iodine were determined by LA-ICP-IDMS in two sediment reference materials (SRM 1646, SRM 2704) and three rock reference samples (GS-N, Granite; BX-N, Bauxite; DT-N, Disthene), which have not been certified for these halogens. The sediment results agree well within the given uncertainties with indicative values by different methods and the results of the rock samples with those obtained by negative thermal ionisation isotope dilution mass spectrometry. The detection limits of LA-ICP-IDMS are 8 [mu]g g-1 for chlorine, 1.7 [mu]g g-1 for bromine, and 0.1 [mu]g g-1 for iodine.

Quantification of Nε-(2-Furoylmethyl)-L-lysine (furosine), Nε-(Carboxymethyl)-L-lysine (CML), Nε-(Carboxyethyl)-L-lysine (CEL) and total lysine through stable isotope dilution assay and tandem mass spectrometry.

Science.gov (United States)

Troise, Antonio Dario; Fiore, Alberto; Wiltafsky, Markus; Fogliano, Vincenzo

2015-12-01

The control of Maillard reaction (MR) is a key point to ensure processed foods quality. Due to the presence of a primary amino group on its side chain, lysine is particularly prone to chemical modifications with the formation of Amadori products (AP), Nε-(Carboxymethyl)-L-lysine (CML), Nε-(Carboxyethyl)-L-lysine (CEL). A new analytical strategy was proposed which allowed to simultaneously quantify lysine, CML, CEL and the Nε-(2-Furoylmethyl)-L-lysine (furosine), the indirect marker of AP. The procedure is based on stable isotope dilution assay followed by liquid chromatography tandem mass spectrometry. It showed high sensitivity and good reproducibility and repeatability in different foods. The limit of detection and the RSD% were lower than 5 ppb and below 8%, respectively. Results obtained with the new procedure not only improved the knowledge about the reliability of thermal treatment markers, but also defined new insights in the relationship between Maillard reaction products and their precursors. Copyright © 2015 Elsevier Ltd. All rights reserved.

Mass spectrometry in nuclear technology - a review of application of thermal ionization mass spectrometry in fuel reprocessing plants. PD-7-1

International Nuclear Information System (INIS)

Dakshinamoorthy, A.

2007-01-01

Mass spectrometry finds the widespread application in nuclear science and technology due to the fact that it can be employed for isotope composition measurements of different elements of interest and also concentration measurements of these elements using isotope dilution techniques. Thermal ionization mass spectrometer (TIMS), Inductively coupled plasma mass spectrometer (ICP-MS) and gas chromatography mass spectrometer (GC-MS) are the different types of mass spectrometers used in nuclear industry for the analyses of isotope composition of special nuclear material, trace impurities in nuclear fuels and components and characterization of various solvents respectively. Among them, TIMS plays a vital role in the nuclear fuel cycle in determining precisely the isotope composition of uranium, plutonium, D/H ratio in heavy water etc. TIMS is an indispensable analytical tool for nuclear material accounting at the input stage of a reprocessing plant by carrying out precise and accurate concentration measurement of plutonium and uranium by isotope dilution mass spectrometry (IDMS). It is the only accepted measurement technique for the purpose because of its high precision, better sensitivity and no quantitative separation is needed. The isotope abundance measurements of uranium and plutonium at this point are also useful for burn-up studies and isotope correlations. Mass spectrometric analysis of uranium and plutonium is also required for nuclear data measurements and calibrating other chemical methods

Stable carbon isotope analyses of nanogram quantities of particulate organic carbon (pollen) with laser ablation nano combustion gas chromatography/isotope ratio mass spectrometry

Science.gov (United States)

Sluijs, Appy; Laks, Jelmer J.; Reichart, Gert‐Jan

2016-01-01

Rationale Analyses of stable carbon isotope ratios (δ 13C values) of organic and inorganic matter remains have been instrumental for much of our understanding of present and past environmental and biological processes. Until recently, the analytical window of such analyses has been limited to samples containing at least several μg of carbon. Methods Here we present a setup combining laser ablation, nano combustion gas chromatography and isotope ratio mass spectrometry (LA/nC/GC/IRMS). A deep UV (193 nm) laser is used for optimal fragmentation of organic matter with minimum fractionation effects and an exceptionally small ablation chamber and combustion oven are used to reduce the minimum sample mass requirement compared with previous studies. Results Analyses of the international IAEA CH‐7 polyethylene standard show optimal accuracy, and precision better than 0.5‰, when measuring at least 42 ng C. Application to untreated modern Eucalyptus globulus (C3 plant) and Zea mays (C4 plant) pollen grains shows a ~ 16‰ offset between these species. Within each single Z. mays pollen grain, replicate analyses show almost identical δ 13C values. Conclusions Isotopic offsets between individual pollen grains exceed analytical uncertainties, therefore probably reflecting interspecimen variability of ~0.5–0.9‰. These promising results set the stage for investigating both δ 13C values and natural carbon isotopic variability between single specimens of a single population of all kinds of organic particles yielding tens of nanograms of carbon. © 2016 The Authors. Rapid Communications in Mass Spectrometry Published by John Wiley & Sons Ltd. PMID:27766694

Isotope Ratio Monitoring Gas Chromatography Mass Spectrometry (IRM-GCMS)

International Nuclear Information System (INIS)

Freeman, K.H.; Ricci, S.A.; Studley, A.; Hayes, J.M.

1989-01-01

On Earth, the C-13 content of organic compounds is depleted by roughly 13 to 23 permil from atmospheric carbon dioxide. This difference is largely due to isotope effects associated with the fixation of inorganic carbon by photosynthetic organisms. If life once existed on Mars, then it is reasonable to expect to observe a similar fractionation. Although the strongly oxidizing conditions on the surface of Mars make preservation of ancient organic material unlikely, carbon-isotope evidence for the existence of life on Mars may still be preserved. Carbon depleted in C-13 could be preserved either in organic compounds within buried sediments, or in carbonate minerals produced by the oxidation of organic material. A technique is introduced for rapid and precise measurement of the C-13 contents of individual organic compounds. A gas chromatograph is coupled to an isotope-ratio mass spectrometer through a combustion interface, enabling on-line isotopic analysis of isolated compounds. The isotope ratios are determined by integration of ion currents over the course of each chromatographic peak. Software incorporates automatic peak determination, corrections for background, and deconvolution of overlapped peaks. Overall performance of the instrument was evaluated by the analysis of a mixture of high purity n-alkanes of know isotopic composition. Isotopic values measured via IRM-GCMS averaged withing 0.55 permil of their conventionally measured values

Using Gas Chromatography/Isotope Ratio Mass Spectrometry to Determine the Fractionation Factor for H2 Production by Hydrogenases

International Nuclear Information System (INIS)

Yang, Hui; Ghandi, H.; Shi, Liang; Kreuzer, Helen W.; Ostrom, Nathaniel; Hegg, Eric L.

2012-01-01

Hydrogenases catalyze the reversible formation of H2, and they are key enzymes in the biological cycling of H2. H isotopes should be a very useful tool in quantifying proton trafficking in biological H2 production processes, but there are several obstacles that have thus far limited the use of this tool. In this manuscript, we describe a new method that overcomes some of these barriers and is specifically designed to measure isotopic fractionation during enzyme-catalyzed H2 evolution. A key feature of this technique is that purified hydrogenases are employed, allowing precise control over the reaction conditions and therefore a high level of precision. A custom-designed high-throughput gas chromatography-isotope ratio mass spectrometer is employed to measure the isotope ratio of the H2. Using this method, we determined that the fractionation factor of H2 production by the (NiFe)-hydrogenase from Desulfivibrio fructosovran is 0.27. This result indicates that, as expected, protons are highly favored over deuterons during H2 evolution. Potential applications of this new method are discussed.

Flux Analysis of Free Amino Sugars and Amino Acids in Soils by Isotope Tracing with a Novel Liquid Chromatography/High Resolution Mass Spectrometry Platform.

Science.gov (United States)

Hu, Yuntao; Zheng, Qing; Wanek, Wolfgang

2017-09-05

Soil fluxomics analysis can provide pivotal information for understanding soil biochemical pathways and their regulation, but direct measurement methods are rare. Here, we describe an approach to measure soil extracellular metabolite (amino sugar and amino acid) concentrations and fluxes based on a 15 N isotope pool dilution technique via liquid chromatography and high-resolution mass spectrometry. We produced commercially unavailable 15 N and 13 C labeled amino sugars and amino acids by hydrolyzing peptidoglycan isolated from isotopically labeled bacterial biomass and used them as tracers ( 15 N) and internal standards ( 13 C). High-resolution (Orbitrap Exactive) MS with a resolution of 50 000 allowed us to separate different stable isotope labeled analogues across a large range of metabolites. The utilization of 13 C internal standards greatly improved the accuracy and reliability of absolute quantification. We successfully applied this method to two types of soils and quantified the extracellular gross fluxes of 2 amino sugars, 18 amino acids, and 4 amino acid enantiomers. Compared to the influx and efflux rates of most amino acids, similar ones were found for glucosamine, indicating that this amino sugar is released through peptidoglycan and chitin decomposition and serves as an important nitrogen source for soil microorganisms. d-Alanine and d-glutamic acid derived from peptidoglycan decomposition exhibited similar turnover rates as their l-enantiomers. This novel approach offers new strategies to advance our understanding of the production and transformation pathways of soil organic N metabolites, including the unknown contributions of peptidoglycan and chitin decomposition to soil organic N cycling.

Flux Analysis of Free Amino Sugars and Amino Acids in Soils by Isotope Tracing with a Novel Liquid Chromatography/High Resolution Mass Spectrometry Platform

Science.gov (United States)

2017-01-01

Soil fluxomics analysis can provide pivotal information for understanding soil biochemical pathways and their regulation, but direct measurement methods are rare. Here, we describe an approach to measure soil extracellular metabolite (amino sugar and amino acid) concentrations and fluxes based on a 15N isotope pool dilution technique via liquid chromatography and high-resolution mass spectrometry. We produced commercially unavailable 15N and 13C labeled amino sugars and amino acids by hydrolyzing peptidoglycan isolated from isotopically labeled bacterial biomass and used them as tracers (15N) and internal standards (13C). High-resolution (Orbitrap Exactive) MS with a resolution of 50 000 allowed us to separate different stable isotope labeled analogues across a large range of metabolites. The utilization of 13C internal standards greatly improved the accuracy and reliability of absolute quantification. We successfully applied this method to two types of soils and quantified the extracellular gross fluxes of 2 amino sugars, 18 amino acids, and 4 amino acid enantiomers. Compared to the influx and efflux rates of most amino acids, similar ones were found for glucosamine, indicating that this amino sugar is released through peptidoglycan and chitin decomposition and serves as an important nitrogen source for soil microorganisms. d-Alanine and d-glutamic acid derived from peptidoglycan decomposition exhibited similar turnover rates as their l-enantiomers. This novel approach offers new strategies to advance our understanding of the production and transformation pathways of soil organic N metabolites, including the unknown contributions of peptidoglycan and chitin decomposition to soil organic N cycling. PMID:28776982

Comparison of liquid chromatography-isotope ratio mass spectrometry (LC/IRMS) and gas chromatography-combustion-isotope ratio mass spectrometry (GC/C/IRMS) for the determination of collagen amino acid δ13C values for palaeodietary and palaeoecological reconstruction.

Science.gov (United States)

Dunn, Philip J H; Honch, Noah V; Evershed, Richard P

2011-10-30

Results are presented of a comparison of the amino acid (AA) δ(13)C values obtained by gas chromatography-combustion-isotope ratio mass spectrometry (GC/C/IRMS) and liquid chromatography-isotope ratio mass spectrometry (LC/IRMS). Although the primary focus was the compound-specific stable carbon isotope analysis of bone collagen AAs, because of its growing application for palaeodietary and palaeoecological reconstruction, the results are relevant to any field where AA δ(13)C values are required. We compare LC/IRMS with the most up-to-date GC/C/IRMS method using N-acetyl methyl ester (NACME) AA derivatives. This comparison involves the analysis of standard AAs and hydrolysates of archaeological human bone collagen, which have been previously investigated as N-trifluoroacetyl isopropyl esters (TFA/IP). It was observed that, although GC/C/IRMS analyses required less sample, LC/IRMS permitted the analysis of a wider range of AAs, particularly those not amenable to GC analysis (e.g. arginine). Accordingly, reconstructed bulk δ(13)C values based on LC/IRMS-derived δ(13)C values were closer to the EA/IRMS-derived δ(13)C values than those based on GC/C/IRMS values. The analytical errors for LC/IRMS AA δ(13)C values were lower than GC/C/IRMS determinations. Inconsistencies in the δ(13)C values of the TFA/IP derivatives compared with the NACME- and LC/IRMS-derived δ(13)C values suggest inherent problems with the use of TFA/IP derivatives, resulting from: (i) inefficient sample combustion, and/or (ii) differences in the intra-molecular distribution of δ(13)C values between AAs, which are manifested by incomplete combustion. Close similarities between the NACME AA δ(13)C values and the LC/IRMS-derived δ(13)C values suggest that the TFA/IP derivatives should be abandoned for the natural abundance determinations of AA δ(13)C values. Copyright © 2011 John Wiley & Sons, Ltd.

Comparison of total body water determinations in lactating women by anthropometry, water displacement, and deuterium isotope dilution

International Nuclear Information System (INIS)

Wong, W.; Butte, N.; Lee, L.; Garza, C.; Klein, P.

1986-01-01

To expand the limited data on the total body water in lactating women, the authors have determined total body water contents, in eight subjects from anthropometric measurements, water displacement, and isotope dilution of deuterium oxide. On the day of the study, their skinfold thicknesses were measured over the biceps and triceps muscles and at the suprailiac and subscapular areas. Their body densities were measured by water displacement. Deuterium oxide was administered orally at 100 mg/kg of body weight. One predose milk sample was collected from each subject. The milk samples were defatted by centrifugation and the milk water was reduced to hydrogen gas for hydrogen isotope ratio measurements by gas-isotope-ratio mass spectrometry. The results indicated that total body water in lactating women estimated from anthropometric measurements was 49.7 +/- 3.3% of body weight, by water displacement was 54.9 +/- 7.2%, and by isotope dilution was 50.8 +/- 3.7%

Comparative determination of sucrose content in sugar beet by polarimetric and isotope dilution methods

Energy Technology Data Exchange (ETDEWEB)

Malec, K; Szuchnik, A [Institute of Nuclear Research, Warsaw (Poland); Rydel, S; Walerianaczyk, E [Instytut Przemyslu Cukrowniczego, Warsaw (Poland)

1976-01-01

The comparative determination of sucrose content in sugar beets has been investigated by following methods: polarimetric, direct isotope dilution and double carrier-isotope dilution analysis. Basing upon the obtained results it has been ascertained, that in the case of worse quality beets the polarimetric determinations differ greatly from isotopic data.

Immunocapture isotope dilution mass spectrometry in response to a pandemic influenza threat.

Science.gov (United States)

Pierce, Carrie L; Williams, Tracie L; Santana, Wanda I; Levine, Marnie; Chen, Li-Mei; Cooper, Hans C; Solano, Maria I; Woolfitt, Adrian R; Marasco, Wayne A; Fang, He; Donis, Ruben O; Barr, John R

2017-09-05

As a result of recent advances in mass spectrometry-based protein quantitation methods, these techniques are now poised to play a critical role in rapid formulation of pandemic influenza vaccines. Analytical techniques that have been developed and validated on seasonal influenza strains can be used to increase the quality and decrease the time required to deliver protective pandemic vaccines to the global population. The emergence of a potentially pandemic avian influenza A (H7N9) virus in March of 2013, prompted the US public health authorities and the vaccine industry to initiate production of a pre-pandemic vaccine for preparedness purposes. To this end, we evaluated the feasibility of using immunocapture isotope dilution mass spectrometry (IC-IDMS) to evaluate the suitability of the underlying monoclonal and polyclonal antibodies (mAbs and pAbs) for their capacity to isolate the H7 hemagglutinin (HA) in this new vaccine for quantification by IDMS. A broad range of H7 capture efficiencies was observed among mAbs tested by IC-IDMS with FR-545, 46/6, and G3 A533 exhibiting the highest cross-reactivity capabilities to H7 of A/Shanghai/2/2013. MAb FR-545 was selected for continued assessment, evaluated by IC-IDMS for mAb reactivity against H7 in the H7N9 candidate vaccine virus and compared with/to reactivity to the reference polyclonal antiserum in allantoic fluid, purified whole virus, lyophilized whole virus and final detergent-split monovalent vaccine preparations for vaccine development. IC-IDMS assessment of FR-545 alongside IC-IDMS using the reference polyclonal antiserum to A/Shanghai/2/2013 and with the regulatory SRID method showed strong correlation and mAb IC-IDMS could have played an important role in the event a potential surrogate potency test was required to be rapidly implemented. Published by Elsevier Ltd.

On the interference of Kr during carbon isotope analysis of methane using continuous-flow combustion–isotope ratio mass spectrometry

NARCIS (Netherlands)

Schmitt, J.; Seth, B.; Bock, M; van der Veen, C.; Möller, L.; Sapart, C.J.; Prokopiou, M.; Sowers, T.; Röckmann, T.; Fischer, H

2013-01-01

Stable carbon isotope analysis of methane ( 13C of CH4) on atmospheric samples is one key method to constrain the current and past atmospheric CH4 budget. A frequently applied measurement technique is gas chromatography (GC) isotope ratio mass spectrometry (IRMS) coupled to a

delta 13C analyses of vegetable oil fatty acid components, determined by gas chromatography--combustion--isotope ratio mass spectrometry, after saponification or regiospecific hydrolysis.

Science.gov (United States)

Woodbury, S E; Evershed, R P; Rossell, J B

1998-05-01

The delta 13C values of the major fatty acids of several different commercially important vegetable oils were measured by gas chromatography--combustion--isotope ratio mass spectrometry. The delta 13C values obtained were found to fall into two distinct groups, representing the C3 and C4 plants classes from which the oils were derived. The delta 13C values of the oils were measured by continuous flow elemental isotope ratio mass spectrometry and were found to be similar to their fatty acids, with slight differences between individual fatty acids. Investigations were then made into the influence on the delta 13C values of fatty acids of the position occupied on the glycerol backbone. Pancreatic lipase was employed to selectively hydrolyse fatty acids from the 1- and 3-positions with the progress of the reaction being followed by high-temperature gas chromatography in order to determine the optimum incubation time. The 2-monoacylglycerols were then isolated by thin-layer chromatography and fatty acid methyl esters prepared. The delta 13C values obtained indicate that fatty acids from any position on the glycerol backbone are isotopically identical. Thus, whilst quantification of fatty acid composition at the 2-position and measurement of delta 13C values of oils and their major fatty acids are useful criteria in edible oil purity assessment, measurement of delta 13C values of fatty acids from the 2-position does not assist with oil purity assignments.

Liquid volumes measurements by isotopic dilution

International Nuclear Information System (INIS)

Herrera M, J.M.

1981-01-01

By the nuclear technique, isotopic dilution industrial liquid volumes may be measured in large size recipients of irregular shapes using radiotracers. In the present work laboratory and pilot test are made with 2 radiotracers for optimizing the technique and later done on an industrial scale, obtaining a maximum deviation of +-2%, some recommendations are given to improve the performance of the technique. (author)

Determination of tungsten in high-alloy steels and heat resisting alloys by isotope dilution-spark source mass spectrometry

International Nuclear Information System (INIS)

Saito, Morimasa; Yamada, Kei; Okochi, Haruno; Hirose, Fumio

1983-01-01

Tungsten in high-alloy steels and heat-resisting alloys was determined by isotope dilution method combined with spark source mass spectrometry by using 183 W enriched tungsten. The spike solution was prepared by fusing tungsten trioxide in sodium carbonate. A high-alloy steel sample was dissolved in the mixture of sulfuric acid and phosphoric acid together with the spike solution; a sample of heat resisting alloy was similarly dissolved in the mixture of hydrochloric acid, nitric acid, sulfuric acid, and phosphoric acid. The solution was evaporated to give dense white fumes. Tungsten was separated from the residue by a conventional cinchonine salt-precipitation method. The salt was ignited, and the residue was mixed with graphite powder and pressed into electrodes. The isotope 183 W and 184 W were measured. The method was applied to the determination of tungsten in JSS and NBS standard high-alloy steels and JAERI standard nickel- and NBS standard cobalt-base heat resisting alloys containing more than 0.05% tungsten. The results were obtained with satisfactory precision and accuracy. However, the results obtained for JSS standard high- speed steels containing molybdenum tended to be significantly lower than the certified values. (author)

Determination of trace sulfur in biodiesel and diesel standard reference materials by isotope dilution sector field inductively coupled plasma mass spectrometry

Energy Technology Data Exchange (ETDEWEB)

Amais, Renata S. [Group of Applied Instrumental Analysis, Department of Chemistry, Federal University of São Carlos, São Carlos, SP (Brazil); Long, Stephen E. [Chemical Sciences Division, National Institute of Standards and Technology, Charleston, SC (United States); Nóbrega, Joaquim A. [Group of Applied Instrumental Analysis, Department of Chemistry, Federal University of São Carlos, São Carlos, SP (Brazil); Christopher, Steven J., E-mail: steven.christopher@nist.gov [Chemical Sciences Division, National Institute of Standards and Technology, Charleston, SC (United States)

2014-01-02

Graphical abstract: -- Highlights: •Sulfur mass fractions are measured below 10 mg kg{sup −1} in diesel fuel materials. •SF-ICP-MS resolves molecular interferences, including oxygen and sulfur hydrides. •A detection limit of 0.7 mg kg{sup −1} (in the fuel sample) was obtained. -- Abstract: A method is described for quantification of sulfur at low concentrations on the order of mg kg{sup −1} in biodiesel and diesel fuels using isotope dilution and sector field inductively coupled plasma mass spectrometry (ID-SF-ICP-MS). Closed vessel microwave-assisted digestion was employed using a diluted nitric acid and hydrogen peroxide decomposition medium to reduce sample dilution volumes. Medium resolution mode was employed to eliminate isobaric interferences at {sup 32}S and {sup 34}S related to polyatomic phosphorus and oxygen species, and sulfur hydride species. The method outlined yielded respective limits of detection (LOD) and limits of quantification (LOQ) of 0.7 mg kg{sup −1} S and 2.5 mg kg{sup −1} S (in the sample). The LOD was constrained by instrument background counts at {sup 32}S but was sufficient to facilitate value assignment of total S mass fraction in NIST SRM 2723b Sulfur in Diesel Fuel Oil at 9.06 ± 0.13 mg kg{sup −1}. No statistically significant difference at a 95% confidence level was observed between the measured and certified values for certified reference materials NIST SRM 2773 B100 Biodiesel (Animal-Based), CENAM DRM 272b and NIST SRM 2723a Sulfur in Diesel Fuel Oil, validating method accuracy.

Study of the matrix specific mass discrimination effects during inductively coupled plasma mass spectrometry isotope ratio measurements

International Nuclear Information System (INIS)

Vassileva, E.; Quetel, Ch.R.

2004-01-01

Sample matrix related effects on mass discrimination during inductively coupled plasma mass spectrometry (ICP-MS) isotope ratio measurements have only been rarely reported. However, they can lead to errors larger than the uncertainty claimed on the ratio results when not properly taken into account or corrected for. These matrix specific affects were experienced during an Isotope Dilution Mass Spectrometry (IDMS) campaign we carried out for the certification of the Cd amount content in some food digest samples (7% acidity and salts content around 450μg g -1 ). Dilution was not possible for Cd only present at the low ng g -1 level. Up to 1% difference was observed on Cd isotope ratio results between measurements performed directly or after matrix separation. This was a significant difference considering that less than 1.5% relative combined uncertainty was eventually estimated for these IDMS measurements. Similar results could be obtained either way after the implementation of necessary corrections. The direct measurement approach associated to a correction for mass discrimination effects using the food digest sample itself (and the IUPAC table values as reference for the natural Cd isotopic composition) was preferred as it was the easiest. Consequently, the impact of matrix effects on mass discrimination during isotope ratio measurements with two types of ICP- MS (quadrupole and magnetic sector instruments) was studied for 4 elements (Li, Cu, Cd and Tl). Samples of varying salinity (up to 0.25%) and acidity (up to 7%) characteristics were prepared using isotopic certified reference materials of these elements. The long term and short-term stability, respectively reproducibility and repeatability, of the results, as well as the evolution of the difference to certified ratio values were monitored. As expected the 13 investigated isotopic ratios were all sensitive to variations in salt and acid concentrations. Our experiments also showed that simultaneous variation

Determination of total cyanide in soil by isotope dilution GC/MS following pentafluorobenzyl derivatization

Energy Technology Data Exchange (ETDEWEB)

Campanella, Beatrice, E-mail: beatrice.campanella@pi.iccom.cnr.it [Università di Pisa, Dipartimento di Chimica e Chimica Industriale, via Moruzzi 13, 56124 Pisa (Italy); Consiglio Nazionale delle Ricerche (CNR), Istituto di Chimica dei Composti Organometallici, UOS di Pisa, via Moruzzi 1, 56124 Pisa (Italy); Biancalana, Lorenzo [Università di Pisa, Dipartimento di Chimica e Chimica Industriale, via Moruzzi 13, 56124 Pisa (Italy); D' Ulivo, Lucia [National Research Council of Canada, 1200 Montreal Road, Ottawa, ON K1A 0R6 (Canada); Onor, Massimo; Bramanti, Emilia [Consiglio Nazionale delle Ricerche (CNR), Istituto di Chimica dei Composti Organometallici, UOS di Pisa, via Moruzzi 1, 56124 Pisa (Italy); Mester, Zoltan; Pagliano, Enea [National Research Council of Canada, 1200 Montreal Road, Ottawa, ON K1A 0R6 (Canada)

2017-04-08

The high toxicity of cyanide, along with its widespread industrial use, has fuelled interest in the development of analytical methods for its determination in complex matrices. In this study, we propose a novel approach for the measurement of total cyanide in soil samples based on single-step derivatization with pentafluorobenzyl bromide (F{sub 5}Bn−Br) followed by quantitation with gas chromatography mass spectrometry in negative chemical ionization mode. The reaction between CN{sup −} and F{sub 5}Bn−Br resulted in the identification of several derivatives such as F{sub 5}Bn−CN, (F{sub 5}Bn)(F{sub 5}Ph)CH−CN, and (F{sub 5}Bn){sub 2}(F{sub 5}Ph)C−CN. The relative proportion between such compounds was dependent on experimental conditions. When a 100 μL aliquot of an alkaline-aqueous extract was reacted with 700 μL of 1.3% F{sub 5}Bn−Br in acetone, the tri-alkylated derivative was the most abundant. In such conditions a detection limit of 0.5 ng/g of CN{sup −} was attained. Soil samples were initially spiked with an alkaline solution of K{sup 13}C{sup 15}N internal standard and suspended in 7.5% aqueous NaOH. Determination of total cyanide was achieved by digestion of the alkaline extract with H{sub 3}PO{sub 4} to produce HCN which was then trapped in 0.1% NaOH in a sealed double vial system, followed by reaction with F{sub 5}Bn−Br. Isotope dilution calibration was chosen for quantitation, and the validity of the novel method was demonstrated by analysis of soil Certified Reference Materials (CRMs) and by spike recovery tests. - Highlights: • A cost-effective, fast and simple method for determination of total cyanide in soil is presented. • A new micro-distillation strategy was developed overcoming the problems of a conventional distillation. • Negative chemical ionization-mass spectrometer has been exploited to obtain a high sensitivity and specificity. • High accuracy was attained for the analysis of certified reference materials with

Application of gas chromatography-mass spectrometry/combustion/isotope ratio mass spectrometry (GC-MS/C/IRMS) to detect the abuse of 17β-estradiol in cattle.

Science.gov (United States)

Janssens, Geert; Mangelinckx, Sven; Courtheyn, Dirk; Prévost, Stéphanie; De Poorter, Geert; De Kimpe, Norbert; Le Bizec, Bruno

2013-07-31

Although the ability to differentiate between endogenous steroids and synthetic homologues on the basis of their (13)C/(12)C isotopic ratio has been known for over a decade, this technique has been scarcely implemented for food safety purposes. In this study, a method was developed using gas chromatography-mass spectrometry/combustion/isotope ratio mass spectrometry (GC-MS/C/IRMS) to demonstrate the abuse of 17β-estradiol in cattle, by comparison of the (13)C/(12)C ratios of the main metabolite 17α-estradiol and an endogenous reference compound (ERC), 5-androstene-3β,17α-diol, in bovine urine. The intermediate precisions were determined as 0.46 and 0.26‰ for 5-androstene-3β,17α-diol and 17α-estradiol, respectively. This is, to the authors' knowledge, the first reported use of GC-MS/C/IRMS for the analysis of steroid compounds for food safety issues.

Quantification of urea in serum by isotope dilution HPLC/MS

International Nuclear Information System (INIS)

Lee, Hwa Shim; Park, Sang Ryoul

2005-01-01

Urea in blood has been measured as an effective marker for diagnosis of renal function. Urea which is the end-product of nitrogen containing metabolites such as proteins is filtered through glomeruli of kidneys and then excreted as urine. If the renal function is deteriorated, the urea concentration in blood will be increased, from which the healthiness of renal function is judged. In order to improve the confidence of diagnosis results, the results must keep traceability chain to certified reference materials, which was certified by primary reference method. In this study, we proposed Isotope Dilution-Liquid Chromatography/Mass Spectrometry (ID-LC/MS) as a candidate primary method, in which 15 N 2 -urea is used as an internal reference material. The developed method is highly accurate in principle and is convenient as it does not require cumbersome derivatization 0.1 mmol/L ammonium chloride was selected as a mobile phase for HPLC because it provide low interference in MS analysis of relatively low molecular weighted urea. HPLC and MS were connected with an ElectroSpry Ionization(ESI) interface of positive mode, which provided high sensitivity and reproducibility. The developed method was validated with internationally recognized reference materials, and we have obtained satisfactory results in an international ring trial. The expanded uncertainty calculated according to ISO guide was 1.8% at 95% confidence interval. The developed method is being used as a primary reference measurement method such as for certification of serum Certified Reference Materials (CRMs)

The Potential of Isotope Ratio Mass Spectrometry (IRMS) and Gas Chromatography-IRMS Analysis of Triacetone Triperoxide in Forensic Explosives Investigations.

Science.gov (United States)

Bezemer, Karlijn D B; Koeberg, Mattijs; van der Heijden, Antoine E D M; van Driel, Chris A; Blaga, Cornelia; Bruinsma, Jildert; van Asten, Arian C

2016-09-01

Studying links between triacetone triperoxide (TATP) samples from crime scenes and suspects can assist in criminal investigations. Isotope ratio mass spectrometry (IRMS) and gas chromatography (GC)-IRMS were used to measure the isotopic compositions of TATP and its precursors acetone and hydrogen peroxide. In total, 31 TATP samples were synthesized with different raw material combinations and reaction conditions. For carbon, a good differentiation and a linear relationship were observed for acetone-TATP combinations. The extent of negative (δ(13) C) fractionation depended on the reaction yield. Limited enrichment was observed for the hydrogen isotope (δ(2) H) values of the TATP samples probably due to a constant exchange of hydrogen atoms in aqueous solution. For oxygen (δ(18) O), the small isotopic range and excess of water in hydrogen peroxide resulted in poor differentiation. GC-IRMS and IRMS data were comparable except for one TATP sample prepared with high acid concentration demonstrating the potential of compound-specific isotope analysis. Carbon IRMS has practical use in forensic TATP investigations. © 2016 American Academy of Forensic Sciences.

Simultaneous determination of platinum group elements and rhenium in rock samples using isotope dilution inductively coupled plasma mass spectrometry after cation exchange separation followed by solvent extraction

International Nuclear Information System (INIS)

Shinotsuka, Kazunori; Suzuki, Katsuhiko

2007-01-01

A simple and precise determination method for platinum group elements (PGEs) and Re in rock samples was developed using isotope dilution coupled with inductively coupled plasma mass spectrometry (ID-ICP-MS). Cation exchange separation was employed for simplicity, because it is applicable to group separation and simultaneous isotopic measurement in contrast with the widely used anion exchange separation which entails separate elution. However, its application to ID-ICP-MS has been limited due to spectral interferences from impurities retained in the PGE fraction even after ion chromatography. To overcome this limitation, solvent extraction using N-benzoyl-N-phenylhydroxylamine (BPHA) in chloroform was successfully applied for further purification. After the examination of optimum experimental parameters in cation exchange separation and solvent extraction using synthetic PGE solution, the established procedure was applied to the determination of PGEs and Re in some geochemical reference materials. The obtained results agreed well with the literature data determined using the different digestion methods (NiS fire assay and the use of a high-pressure asher) within the analytical uncertainties of each other. Significant difference in reproducibility between Ru, Ir, Pt and Os group, and Pd and Re group was observed in the results for BHVO-2 and JA-2. By considering the error factors affecting analytical reproducibility, we concluded that the difference is ascribed to the sample heterogeneity of minor minerals enriched in Ru, Ir, Pt and Os

Characterization of the designer drug deschloroketamine (2-methylamino-2-phenylcyclohexanone) by gas chromatography/mass spectrometry, liquid chromatography/high-resolution mass spectrometry, multistage mass spectrometry, and nuclear magnetic resonance.

Science.gov (United States)

Frison, Giampietro; Zamengo, Luca; Zancanaro, Flavio; Tisato, Francesco; Traldi, Pietro

2016-01-15

Clinical and forensic toxicology laboratories are challenged every day by the analytical aspects of the new psychoactive substances phenomenon. In this study we describe the analytical characterization of a new ketamine derivative, deschloroketamine (2-methylamino-2-phenylcyclohexanone), contained in seized powders. The analytical techniques employed include gas chromatography/mass spectrometry (GC/MS), liquid chromatography/electrospray ionization coupled with Orbitrap high-resolution/MS (LC/ESI-HRMS), multistage MS (ESI-MS(n)), and NMR. The LC/ESI-HRMS analyses consisted of accurate mass measurements of MH(+) ions in full-scan mode; comparison of experimental and calculated MH(+) isotopic patterns; and examination of the isotopic fine structure (IFS) of the M + 1, M + 2, M + 3 isotopic peaks relative to the monoisotopic M + 0 peak. The collision-induced product ions of the MH(+) ions were studied by both HRMS and MS(n). (1)H and (13)C NMR measurements were carried out to confirm the chemical structure of the analyte. The EI mass spectra obtained by GC/MS analysis showed the presence of molecular ions at m/z 203, and main fragment ions at m/z 175, 174, 160, 147, 146, and 132. The application of LC/ESI-HRMS allowed us to obtain: the accurate mass of deschloroketamine MH(+) ions with a mass accuracy of 1.47 ppm; fully superimposable experimental and calculated MH(+) isotopic patterns, with a relative isotopic abundance value of 3.69 %; and the IFS of the M + 1, M + 2, M + 3 isotopic peaks completely in accordance with theoretical values. Examination of the product ions of MH(+), as well as the study of both (1)H and (13)C NMR spectra, enabled the full characterization of the molecular structure of deschloroketamine. The combination of the employed analytical techniques allowed the characterization of the seized psychoactive substance, in spite of the lack of a reference standard. Deschloroketamine is a ketamine analogue considered to be

Full quantification of selenium species by RP and AF-ICP-qMS with on-line isotope dilution in serum samples from mercury-exposed people supplemented with selenium-enriched yeast

DEFF Research Database (Denmark)

Li, Yu-Feng; Hu, Liang; Li, Bai

2011-01-01

and affinity chromatography (AF) hyphenated to inductively coupled plasma-(quadrupole) mass spectrometry (ICP-qMS) with post-column isotope dilution analysis (IDA) and a collision cell technique (CCT). Different Se species like inorganic Se (Se4+ and Se6+), selenocystine (SeCys), selenomethionine (Se...... L−1 for GPx and other non-retained Se compounds, 1.0 μg Se L−1 for SelP and 1.2 μg Se L−1 for SeAlb, 1.3 μg Se L−1 for inorganic Se; 1.2 μg Se L−1 for SeCys; 1.1 μg Se L−1 for SeMet, respectively....

Determination of molybdenum in plant reference material by thermal-ionization isotope-dilution mass spectrometry

International Nuclear Information System (INIS)

Saumer, M.; Gantner, E.; Reinhardt, J.; Ache, H.J.

1992-01-01

An analytical method is described for the determination of the concentration and the isotopic composition of molybdenum in plant samples using thermal ionization mass spectrometry. After microwave acid digestion and liquid-liquid extractive separation with Amberlite LA-2, the molybdenum isotopes are measured as MoO 3 - -ions in a quadrupole mass spectrometer. In all cases, the relative standard deviation of the measurements of both natural and spike molybdenum was better than 3% for all ratios measured. The concentration of molybdenum found in three different plant reference materials agreed well with the certified values. (orig.)

The relation of plasma octopamine to hepatic encephalopathy studied with stable isotope dilution technique

International Nuclear Information System (INIS)

Zhang Jianhua

1992-01-01

In order to investigate the relationship between octopamine and hepatic encephalopathy, plasma octopamine content of normal adults and hepatic patients (compensated or de-compensated cirrhotic, patients with encephalopathy) were determined with isotope dilution and GCMS technique, 200 ng of [1, 1-D]-octopamine was added to each sample as internal standard. After the de-proteinized plasma was subjected to cation exchange chromatography, the amine fraction was derivatized with PFP and analyzed with GCMS using the selected ion monitoring technique. The result showed that the level of plasma octopamine was significantly elevated in patients with encephalopathy. Since this method is sensitive and specific, it is readily applicable to the analysis of a few nano grams of octopamine

Fractionation of lithium isotopes in cation-exchange chromatography

International Nuclear Information System (INIS)

Oi, Takao; Kawada, Kazuhiko; Kakihana, Hidetake; Hosoe, Morikazu

1991-01-01

Various methods for lithium isotope separation have been developed, and their applicability to large-scale enriched lithium isotope production has been assessed. Ion-exchange chromatography is one such method. Cation-exchange chromatography of lithium was carried out to investigate the lithium isotope effect in aqueous ion-exchange systems. The heavier isotope. 7 Li, was preferentially fractionated into the resin phase in every experiment conducted, and this result is consistent with the results of previous work. The value of the separation factor was 1.00089-1.00171 at 25C. A comparison of lithium isotope effect with those of potassium and rubidium indicated that the isotope effect originating from hydration is larger than the effect due to phase change for lithium, while the opposite is the case with potassium and rubidium

Radioimmunoassay and liquid-chromatographic analysis for free cortisol in urine compared with isotope dilution-mass spectrometry

International Nuclear Information System (INIS)

Lantto, O.

1982-01-01

Three different routine methods for analysis for urinary cortisol with those by a highly specific reference method based on isotope dilution-mass spectrometry (I) were compared. A ''high-performance'' liquid-chromatographic method (II) gave the most comparable results (regression coefficient 0.86, intercept 9 nmol/L). For some urines much lower values were obtained by I than by II. Two radioimmunoassay (III) methods, one involving direct assay and one involving extraction, gave less-accurate results (regression coefficients of 1.87 and 1.52 and intercepts of 86 and 12 nmol/L, respectively), although values obtained by III and by I correlated well (r = 0.95-0.99), indicating a relation between the free cortisol and the compounds interfering in III. The apparent accuracy for the extraction method was improved by using as calibration standards urine samples previously assayed by I (regression coefficient 0.90, intercept 6 nmol/L). All four methods investigated showed a statistically significant sex-related difference in 24-h urinary cortisol excretion; evidently such a finding should be a prerequisite in any such method proposed for routine use

Improvement of sample preparation for input plutonium accountability measurement by isotope dilution gammy-ray spectroscopy

International Nuclear Information System (INIS)

Nishida, K.; Kuno, Y.; Sato, S.; Masui, J.; Li, T.K.; Parker, J.L.; Hakkila, E.A.

1992-01-01

The sample preparation method for the isotope dilution gamma-ray spectrometry (IDGS) technique has been further improved for simultaneously determining the plutonium concentration and isotopic composition of highly irradiated spent-fuel dissolver solutions. The improvement includes using ion-exchange filter papers (instead of resin beads, as in two previous experiments) for better separation and recovery of plutonium from fission products. The results of IDGS measurements for five dissolver solutions are in good agreement with those by mass spectrometry with ∼0.4% for plutonium concentration and ∼0.1% for 239 Pu isotopic composition. The precision of the plutonium concentration is ∼1% with a 1-h count time. The technique could be implemented as an alternative method for input accountability and verification measurements in reprocessing plants

Single-run determination of polybrominated diphenyl ethers (PBDEs) di- to deca-brominated in fish meal, fish oil and fish feed by isotope dilution: Application of automated sample purification and gas chromatography/ion trap tandem mass spectrometry (GC/ITMS)

International Nuclear Information System (INIS)

Blanco, Sonia Lucia; Vieites, Juan M.

2010-01-01

The present paper describes the application of automated cleanup and fractionation procedures of the Power Prep system (Fluid Management Systems) for the determination of polybrominated diphenyl ethers (PBDEs) in feeding stuffs and fish meal and oil. Gas chromatography (GC) separation followed by ion trap tandem mass spectrometry detection in EI mode (ITMS) allowed the analysis of di- to deca-BDEs in the samples matrices used in fish aquaculture. The method developed enabled the determination of 26 native PBDE congeners and 11 13 C 12 -labelled congeners, including deca-BDE 209, in a single-run analysis, using isotope dilution. The automated cleanup, consisting of a succession of multilayer silica and basic alumina columns previously applied by Wyrzykowska et al. (2009) in combustion flue gas, was succesfully applied in our complex matrices. The method allowed an increase in productivity, i.e. lower time was required to process samples, and simultaneous purification of several samples was achieved at a time, reducing analyst dedication and human error input. Average recoveries of 43-96% were obtained. GC/ITMS can overcome the complexity originating from the sample matrix, eliminating matrix effects by tandem MS, to enable the detection of congeners penta- to nona-BDEs where interferent masses were present. The provisional detection limits, estimated in the samples, were 5-30 pg for di-, tri-, tetra-, and penta-BDEs, 20-65 pg for hexa-, hepta-, octa- and nona-BDEs, and 105 pg for deca-BDE. Reduction of deca-BDE 209 blank values is of concern to ongoing research. Good accuracy was obtained by application of the whole procedure, representing an efficient, low-cost and fast alternative for routine analyses.

Total body skeletal muscle mass: estimation by creatine (methyl-d3) dilution in humans

Science.gov (United States)

Walker, Ann C.; O'Connor-Semmes, Robin L.; Leonard, Michael S.; Miller, Ram R.; Stimpson, Stephen A.; Turner, Scott M.; Ravussin, Eric; Cefalu, William T.; Hellerstein, Marc K.; Evans, William J.

2014-01-01

Current methods for clinical estimation of total body skeletal muscle mass have significant limitations. We tested the hypothesis that creatine (methyl-d3) dilution (D3-creatine) measured by enrichment of urine D3-creatinine reveals total body creatine pool size, providing an accurate estimate of total body skeletal muscle mass. Healthy subjects with different muscle masses [n = 35: 20 men (19–30 yr, 70–84 yr), 15 postmenopausal women (51–62 yr, 70–84 yr)] were housed for 5 days. Optimal tracer dose was explored with single oral doses of 30, 60, or 100 mg D3-creatine given on day 1. Serial plasma samples were collected for D3-creatine pharmacokinetics. All urine was collected through day 5. Creatine and creatinine (deuterated and unlabeled) were measured by liquid chromatography mass spectrometry. Total body creatine pool size and muscle mass were calculated from D3-creatinine enrichment in urine. Muscle mass was also measured by magnetic resonance imaging (MRI), dual-energy x-ray absorptiometry (DXA), and traditional 24-h urine creatinine. D3-creatine was rapidly absorbed and cleared with variable urinary excretion. Isotopic steady-state of D3-creatinine enrichment in the urine was achieved by 30.7 ± 11.2 h. Mean steady-state enrichment in urine provided muscle mass estimates that correlated well with MRI estimates for all subjects (r = 0.868, P creatine dose determined by urine D3-creatinine enrichment provides an estimate of total body muscle mass strongly correlated with estimates from serial MRI with less bias than total lean body mass assessment by DXA. PMID:24764133

Compound-specific isotope analysis of light elements using gas chromatography/combustion/isotope ratio mass spectrometry (GC/C/IRMS) and its application to geochemistry

International Nuclear Information System (INIS)

Naraoka, Hiroshi; Yamada, Keita; Matsumoto, Kohei; Ishiwatari, Ryoshi

1997-01-01

Compound-specific isotope analysis has been developed recently using gas chromatography/combustion/mass spectrometry (GC/C/IRMS). This paper summarizes principles and progress of GC/C/IRMS, and reviews recent some important works using this new method. GC/C/IRMS is a novel tool for (1) biomarker analysis in sediments and living matter, (2) paleoenvironment analysis including reconstruction of ancient biogeochemical processes, (3) geochemical cycle study of organic compounds in a terrestrial-marine system, (4) evaluation of maturity and diagenesis of organic matter including petroleum formation, (5) ecological analysis, (6) evaluation of anthropologenic pollution in environment, (7) detection of extraterrestrial organic compounds and the formation mechanism study, (8) tracer studies in environment. (author)

Cortisol production rates measured by liquid chromatography/mass spectrometry

International Nuclear Information System (INIS)

Esteban, N.V.; Yergey, A.L.

1990-01-01

Cortisol production rates (FPRs) in physiologic and pathologic states in humans have been investigated over the past 30 years. However, there has been conflicting evidence concerning the validity of the currently accepted value of FPRs in humans (12 to 15 mg/m2/d) as determined by radiotracer methodology. The present study reviews previous methods proposed for the measurement of FPRs in humans and discusses the applications of the first method for the direct determination of 24-hour plasma FPRs during continuous administration of a stable isotope, using a thermospray high-pressure liquid chromatography-mass spectrometry technique. The technique is fast, sensitive, and, unlike gas chromatography-mass spectrometry methods, does not require derivatization, allowing on-line detection and quantification of plasma cortisol after a simple extraction procedure. The results of determination of plasma FPRs by stable tracer/mass spectrometry are directly in units of mass/time and, unlike radiotracer methods, are independent of any determination of volume of distribution or cortisol concentration. Our methodology offers distinct advantages over radiotracer techniques in simplicity and reliability since only single measurements of isotope ratios are required. The technique was validated in adrenalectomized patients. Circadian variations in daily FRPs were observed in normal volunteers, and, to date, results suggest a lower FRP in normal children and adults than previously believed. 88 references

Combination of pentafluorophenylhydrazine derivatization and isotope dilution LC-MS/MS techniques for the quantification of apurinic/apyrimidinic sites in cellular DNA.

Science.gov (United States)

Li, Jie; Leung, Elvis M K; Choi, Martin M F; Chan, Wan

2013-05-01

Apurinic/apyrimidinic (AP) sites are common DNA lesions arising from spontaneous hydrolysis of the N-glycosidic bond and base-excision repair mechanisms of the modified bases. Due to the strong association of AP site formation with physically/chemically induced DNA damage, quantifying AP sites provides important information for risk assessment of exposure to genotoxins and oxidative stress. However, rigorous quantification of AP sites in DNA has been hampered by technical problems relating to the sensitivity and selectivity of existing analytical methods. We have developed a new isotope dilution liquid chromatography-coupled tandem mass spectrometry (LC-MS/MS) method for the rigorous quantification of AP sites in genomic DNA. The method entails enzymatic digestion of AP site-containing DNA by endo- and exonucleases, derivatization with pentafluorophenylhydrazine (PFPH), addition of an isotopically labeled PFPH derivative as internal standard, and quantification by LC-MS/MS. The combination of PFPH derivatization with LC-MS/MS analysis on a triple quadrupole mass spectrometer allows for sensitive and selective quantification of AP sites in DNA at a detection limit of 6.5 fmol, corresponding to 4 AP sites/10(9) nt in 5 μg of DNA, which is at least ten times more sensitive than existing analytical methods. The protocol was validated by AP site-containing oligonucleotides and applied in quantifying methyl methanesulfonate-induced formation of AP sites in cellular DNA.

Isotope dilution analysis of environmental samples

International Nuclear Information System (INIS)

Tolgyessy, J.; Lesny, J.; Korenova, Z.; Klas, J.; Klehr, E.H.

1986-01-01

Isotope dilution analysis has been used for the determination of several trace elements - especially metals - in a variety of environmental samples, including aerosols, water, soils, biological materials and geological materials. Variations of the basic concept include classical IDA, substoichiometric IDA, and more recently, sub-superequivalence IDA. Each variation has its advantages and limitations. A periodic chart has been used to identify those elements which have been measured in environmental samples using one or more of these methods. (author)

Simultaneous quantification of endogenous and exogenous plasma glucose by isotope dilution LC-MS/MS with indirect MRM of the derivative tag.

Science.gov (United States)

Yu, Lingling; Wen, Chao; Li, Xing; Fang, Shiqi; Yang, Lichuan; Wang, Tony; Hu, Kaifeng

2018-03-01

Quantification of endogenous and exogenous plasma glucose can help more comprehensively evaluate the glucose metabolic status. A ratio-based approach using isotope dilution liquid chromatography tandem mass spectrometry (ID LC-MS/MS) with indirect multiple reaction monitoring (MRM) of the derivative tag was developed to simultaneously quantify endo-/exogenous plasma glucose. Using diluted D-[ 13 C 6 ] glucose as tracer of exogenous glucose, 12 C 6 / 13 C 6 glucoses were first derivatized and then data were acquired in MRM mode. The metabolism of exogenous glucose can be tracked and the concentration ratio of endo/exo-genous glucose can be measured by calculating the endo-/exo-genous glucose concentrations from peak area ratio of specific daughter ions. Joint application of selective derivatization and MRM analysis not only improves the sensitivity but also minimizes the interference from the background of plasma, which warrants the accuracy and reproducibility. Good agreement between the theoretical and calculated concentration ratios was obtained with a linear correlation coefficient (R) of 0.9969 in the range of D-glucose from 0.5 to 20.0 mM, which covers the healthy and diabetic physiological scenarios. Satisfactory reproducibility was obtained by evaluation of the intra- and inter-day precisions with relative standard deviations (RSDs) less than 5.16%, and relative recoveries of 85.96 to 95.92% were obtained at low, medium, and high concentration, respectively. The method was successfully applied to simultaneous determination of the endo-/exogenous glucose concentration in plasma of non-diabetic and type II diabetic cynomolgus monkeys. Graphical Abstract The scheme of the proposed ratio-based approach using isotope dilution LC-MS/MS with indirect MRM of the derivative tag for simultaneous quantification of endogenous and exogenous plasma glucose.

Determination of Cd, Pb, Zn and Cu in Sediment Compartments by Sequential Extraction and Isotope Dilution Inductively Coupled Plasma Mass Spectrometry (ID-ICP-MS

Directory of Open Access Journals (Sweden)

Gardolinski Paulo C. F. C.

2002-01-01

Full Text Available Trace concentrations of Cd, Cu, Pb and Zn in four different sediment fractions extracted in sequence were determined by isotope dilution inductively coupled mass spectrometry (IDICPMS. The metals from each fraction were extracted following the sequential extraction procedure recommended by the Bureau Commun de Référence (BCR of the Commission of the European Communities. As an alternative to external calibration, the elements were quantified by spiking the extracted solutions with 112Cd, 63Cu, 208Pb and 66Zn and application of isotope dilution. The proposed approach was applied to a sample collected from a lake and two standard reference materials, NIST2704 river sediment from the National Institute of Standards & Technology and the BCR-277 estuarine sediment. Detection limits, for each extracted solution, varied from 0.31 to 0.53 mug L¹ for Cd, 0.92 to 2.9 mug L¹ for Cu, 0.22 to 1.1 mug L¹ for Pb and 1.3 to 7.6 mug L¹ for Zn. The sum of the metals concentration in the different fractions was compatible with 95% confidence level found amounts obtained with complete digestion of the samples and with the certified values of the standard reference materials.

Simultaneous Detection of Androgen and Estrogen Abuse in Breeding Animals by Gas Chromatography-Mass Spectrometry/Combustion/Isotope Ratio Mass Spectrometry (GC-MS/C/IRMS) Evaluated against Alternative Methods.

Science.gov (United States)

Janssens, Geert; Mangelinckx, Sven; Courtheyn, Dirk; De Kimpe, Norbert; Matthijs, Bert; Le Bizec, Bruno

2015-09-02

The administration of synthetic homologues of naturally occurring steroids can be demonstrated by measuring (13)C/(12)C isotopic ratios of their urinary metabolites. Gas chromatography-mass spectrometry/combustion/isotope ratio mass spectrometry (GC-MS/C/IRMS) was used in this study to appraise in a global approach isotopic deviations of two 17β-testosterone metabolites (17α-testosterone and etiocholanolone) and one 17β-estradiol metabolite (17α-estradiol) together with those of 5-androstene-3β,17α-diol as endogenous reference compound (ERC). Intermediate precisions of 0.35‰, 1.05‰, 0.35‰, and 0.21‰, respectively, were observed (n = 8). To assess the performance of the analytical method, a bull and a heifer were treated with 17β-testosterone propionate and 17β-estradiol-3-benzoate. The sensitivity of the method permitted the demonstration of 17β-estradiol treatment up to 24 days. For 17β-testosterone treatment, the detection windows were 3 days and 24 days for the bull and the heifer, respectively. The capability of GC-MS/C/IRMS to demonstrate natural steroid abuse for urinary steroids was eventually compared to those of mass spectrometry (LC-MS/MS) when measuring intact steroid esters in blood and hair.

Boron isotopic enrichment by displacement chromatography

International Nuclear Information System (INIS)

Mohapatra, K.K.; Bose, Arun

2014-01-01

10 B enriched boron is used in applications requiring high volumetric neutron absorption (absorption cross section- 3837 barn for thermal and 1 barn for 1 MeV fast neutron). It is used in fast breeder reactor (as control rod material), in neutron counter, in Boron Neutron Capture Therapy etc. Owing to very small separation factor, boron isotopic enrichment is a complex process requiring large number of separation stages. Heavy Water Board has ventured in industrial scale production of 10 B enriched boron using Exchange Distillation Process as well as Ion Displacement Chromatography Process. Ion Displacement Chromatography process is used in Boron Enrichment Plant at HWP, Manuguru. It is based on isotopic exchange between borate ions (B(OH) 4 - ) on anion exchange resin and boric acid passing through resin. The isotopic exchange takes place due to difference in zero point energy of 10 B and 11 B

Quantification of four artificial sweeteners in Finnish surface waters with isotope-dilution mass spectrometry

International Nuclear Information System (INIS)

Perkola, Noora; Sainio, Pirjo

2014-01-01

The artificial sweeteners sucralose (SCL), acesulfame (ACS), saccharin (SAC), and cyclamate (CYC) have been detected in environmental waters in Europe and North America. Higher environmental levels are expected in view of the increasing consumption of these food additives. In this study, an isotope-dilution mass spectrometry (IDMS) LC–MS/MS method was developed and validated for quantifying the four artificial sweeteners in boreal lakes (n = 3) and rivers (n = 12). The highest concentrations of ACS, SAC, CYC and SCL were 9,600, 490, 210 and 1000 ng/L, respectively. ACS and SAC were detected in all studied samples, and CYC and SCL in 98% and 56% of the samples. Seasonal trends of ACS and SAC were observed in some rivers. ACS and SCL concentrations in rivers correlated linearly with population equivalents of the wastewater treatment plants in the catchment areas, whereas SAC and CYC concentrations depend more on the source. -- Highlights: • A reliable method for analysing artificial sweeteners in water was validated. • Artificial sweeteners were quantified in boreal rivers and lakes. • Most concentrations were in accordance with previous European studies. • Acesulfame and saccharine concentrations were high in the most contaminated rivers. • Correlation observed between concentrations and mean water throughflow in rivers. -- High concentrations of artificial sweeteners were obtained, which indicates slow or negligible degradation of these compounds in boreal surface waters

Elemental labelling combined with liquid chromatography inductively coupled plasma mass spectrometry for quantification of biomolecules: A review

Science.gov (United States)

Kretschy, Daniela; Koellensperger, Gunda; Hann, Stephan

2012-01-01

This article reviews novel quantification concepts where elemental labelling is combined with flow injection inductively coupled plasma mass spectrometry (FI-ICP-MS) or liquid chromatography inductively coupled plasma mass spectrometry (LC–ICP-MS), and employed for quantification of biomolecules such as proteins, peptides and related molecules in challenging sample matrices. In the first sections an overview on general aspects of biomolecule quantification, as well as of labelling will be presented emphasizing the potential, which lies in such methodological approaches. In this context, ICP-MS as detector provides high sensitivity, selectivity and robustness in biological samples and offers the capability for multiplexing and isotope dilution mass spectrometry (IDMS). Fundamental methodology of elemental labelling will be highlighted and analytical, as well as biomedical applications will be presented. A special focus will lie on established applications underlining benefits and bottlenecks of such approaches for the implementation in real life analysis. Key research made in this field will be summarized and a perspective for future developments including sophisticated and innovative applications will given. PMID:23062431

Quantitative Isotope-Dilution High-Resolution-Mass-Spectrometry Analysis of Multiple Intracellular Metabolites in Clostridium autoethanogenum with Uniformly 13C-Labeled Standards Derived from Spirulina.

Science.gov (United States)

Schatschneider, Sarah; Abdelrazig, Salah; Safo, Laudina; Henstra, Anne M; Millat, Thomas; Kim, Dong-Hyun; Winzer, Klaus; Minton, Nigel P; Barrett, David A

2018-04-03

We have investigated the applicability of commercially available lyophilized spirulina ( Arthrospira platensis), a microorganism uniformly labeled with 13 C, as a readily accessible source of multiple 13 C-labeled metabolites suitable as internal standards for the quantitative determination of intracellular bacterial metabolites. Metabolites of interest were analyzed by hydrophilic-interaction liquid chromatography coupled with high-resolution mass spectrometry. Multiple internal standards obtained from uniformly (U)- 13 C-labeled extracts from spirulina were used to enable isotope-dilution mass spectrometry (IDMS) in the identification and quantification of intracellular metabolites. Extraction of the intracellular metabolites of Clostridium autoethanogenum using 2:1:1 chloroform/methanol/water was found to be the optimal method in comparison with freeze-thaw, homogenization, and sonication methods. The limits of quantification were ≤1 μM with excellent linearity for all of the calibration curves ( R 2 ≥ 0.99) for 74 metabolites. The precision and accuracy were found to be within relative standard deviations (RSDs) of 15% for 49 of the metabolites and within RSDs of 20% for all of the metabolites. The method was applied to study the effects of feeding different levels of carbon monoxide (as a carbon source) on the central metabolism and Wood-Ljungdahl pathway of C. autoethanogenum grown in continuous culture over 35 days. Using LC-IDMS with U- 13 C spirulina allowed the successful quantification of 52 metabolites in the samples, including amino acids, carboxylic acids, sugar phosphates, purines, and pyrimidines. The method provided absolute quantitative data on intracellular metabolites that was suitable for computational modeling to understand and optimize the C. autoethanogenum metabolic pathways active in gas fermentation.

Amino acid δ13C analysis of hair proteins and bone collagen using liquid chromatography/isotope ratio mass spectrometry

DEFF Research Database (Denmark)

Raghavan, Maanasa; McCullagh, James S. O.; Lynnerup, Niels

2010-01-01

We report a novel method for the chromatographic separation and measurement of stable carbon isotope ratios (delta(13)C) of individual amino acids in hair proteins and bone collagen using the LC-IsoLink system, which interfaces liquid chromatography (LC) with isotope ratio mass spectrometry (IRMS......). This paper provides baseline separation of 15 and 13 of the 18 amino acids in bone collagen and hair proteins, respectively. We also describe an approach to analysing small hair samples for compound-specific analysis of segmental hair sections. The LC/IRMS method is applied in a historical context...... by the delta(13)C analysis of hair proteins and bone collagen recovered from six individuals from Uummannaq in Greenland. The analysis of hair and bone amino acids from the same individual, compared for the first time in this study, is of importance in palaeodietary reconstruction. If hair proteins can be used...

Dilute-and-shoot coupled to nanoflow liquid chromatography high resolution mass spectrometry for the determination of drugs of abuse and sport drugs in human urine.

Science.gov (United States)

Alcántara-Durán, Jaime; Moreno-González, David; Beneito-Cambra, Miriam; García-Reyes, Juan F

2018-05-15

In this work, a sensitive nanoflow liquid chromatography high-resolution mass spectrometry screening method has been developed for the determination of multiclass drugs of abuse and sport drugs in human urine. 81 drugs belonging to different multiclass pharmaceuticals were targeted. The method is based on the use of a nanoLC column (75 µm × 150 mm, 3 µm particle size and 100 Å pore) with the nanospray emitter tip integrated so that dead volumes are significantly minimized. Data acquisition method included both full-scan and all ion fragmentation experiments using an Orbitrap analyser (Q-Exactive) operated in the positive ionization mode. To increase laboratory throughput, a dilute-and-shoot methodology has been tested and proposed, based solely on direct urine dilution without further sample workup. Matrix effects were evaluated, showing a negligible effect for all studied compounds when a dilution 1:50 was implemented. Despite this high-dilution factor, limits of quantification were still satisfactory, with values below 5 µg L -1 in most cases, being lower than their minimum required performance limits correspond established by the World Anti-Doping Agency. Therefore, the use of the dilute-and-shoot method with the enhanced sensitivity provided by nanoflow LC setup could be useful tool for the determination of studied compounds in drug testing, thus increasing laboratory performance, because a minimum sample treatment steps are required. Copyright © 2018 Elsevier B.V. All rights reserved.

Calcium isotope fractionation in liquid chromatography with benzo-18-crown-6 resin in aqueous hydrobromic acid medium

International Nuclear Information System (INIS)

Sato, Takuya; Oi, Takao

2015-01-01

Liquid chromatography operated in a breakthrough mode was employed to study calcium isotope fractionation in the aqueous hydrobromic acid medium. Highly porous silica beads, the inner pores of which were embedded with a benzo-18-crown-6 ether resin, were used as column packing material. Enrichment of heavier isotopes of calcium was observed in the frontal part of respective calcium chromatograms. The values of the isotope fractionation coefficient were on the order of 10 -3 . The observed isotope fractionation coefficient was dependent on the concentration of hydrobromic acid in the calcium feed solution; a higher HBr concentration resulted in a smaller fractionation coefficient value. The present calcium isotope effects were most probably mass-dependent, indicating that they mostly came from isotope effects based on molecular vibration. Molecular orbital calculations supported the present experimental results in a qualitative fashion. Chromatography operated in aqueous HBr media is a better system of Ca isotope separation than that operated in aqueous HCl media. (author)

Water Metabolism of Walruses by Isotope Dilution

DEFF Research Database (Denmark)

Acquarone, M.; Born, E. W.; Chwalibog, A.

was sampled via an epidural catheter, at regular intervals, for up to seven hours after the initial enrichment to assess isotope equilibration in the body water pools. Five individuals returned to the haul-out after feeding trips of varying duration (158±86 hr, 44-287 hr) where they were immobilized again......In August 2000, the hydrogen isotope dilution method was used on 7 adult male Atlantic walruses (Odobenus rosmarus rosmarus) (weight: 1197±148 kg, mean±SD, range 1013-1508 kg) at a terrestrial haul-out in Northeastern Greenland to determine their body water pool sizes and body water turnover rates....... During immobilization by use of etorphine HCl (reversed with diprenorphine HCl), a first blood sample was taken to measure background isotope levels. The animals were then enriched with deuterium oxide by infusion into the epidural vein. During recovery, while the animals were still on the beach, blood...

Total and species-specific quantitative analyses of trace elements in sediment by isotope dilution inductively coupled plasma mass spectrometry

International Nuclear Information System (INIS)

Inagaki, Kazumi; Takatsu, Akiko; Yarita, Takashi; Okamoto, Kensaku; Chiba, Koichi

2009-01-01

Isotope dilution inductively coupled plasma mass spectrometry (ID-ICP-MS) is one of the reliable methods for total and species-specific quantitative analysis of trace elements. However, several technical problems (e.g. spectral interference caused from sample constituents) should be overcome to obtain reliable analytical results when environmental samples are analyzed by ID-ICP-MS. In our laboratory, various methods based on ID-ICP-MS have been investigated for reliable quantitative analyses of trace elements in environmental samples. In this paper, coprecipitate separation/ID-ICP-MS for the determination of trace elements in sediment, cation exchange disk filtration/ID-ICP-MS for the determination of selenium in sediment, species-specific ID-ICP-MS using 118 Sn/labeled organotin compounds for the determination of butyltins and phenyltins, and the application of the ID-ICP-MS methods to the certification of sediment reference materials are described. (author)

Abundance of four sulfur mustard-DNA adducts ex vivo and in vivo revealed by simultaneous quantification in stable isotope dilution-ultrahigh performance liquid chromatography-tandem mass spectrometry.

Science.gov (United States)

Yue, Lijun; Wei, Yuxia; Chen, Jia; Shi, Huiqin; Liu, Qin; Zhang, Yajiao; He, Jun; Guo, Lei; Zhang, Tingfen; Xie, Jianwei; Peng, Shuangqing

2014-04-21

Sulfur mustard (SM) is a highly reactive alkylating vesicant and causes blisters upon contact with skin, eyes, and respiratory organs. It covalently links with DNAs by forming four mono- or cross-link adducts. In this article, the reference standards of SM-DNA adducts and deuterated analogues were first synthesized with simplified procedures containing only one or two steps and using less toxic chemical 2-(2-chloroethylthio)ethanol or nontoxic chemical thiodiglycol as starting materials. A sensitive and high-throughput simultaneous quantification method of N(7)-[2-[(2-hydroxyethyl)thio]-ethyl]guanine (N(7)-HETEG), O(6)-[2-[(2-hydroxyethyl)thio]-ethyl]guanine (O(6)-HETEG), N(3)-[2-[(2-hydroxyethyl)thio]-ethyl]adenine (N(3)-HETEA), and bis[2-(guanin-7-yl)ethyl]sulfide (Bis-G) in the Sprague-Dawley rat derma samples was developed by stable isotope dilution-ultrahigh performance liquid chromatography-tandem mass spectrometry (ID-UPLC-MS/MS) with the aim of revealing the real metabolic behaviors of four adducts. The method was validated, the limit of detection (S/N ratio greater than 10) was 0.01, 0.002, 0.04, and 0.11 fmol on column for N(7)-HETEG, O(6)-HETEG, Bis-G, and N(3)-HETEA, respectively, and the lower limit of quantification (S/N ratio greater than 20) was 0.04, 0.01, 0.12, and 0.33 fmol on column for N(7)-HETEG, O(6)-HETEG, Bis-G, and N(3)-HETEA, respectively. The accuracy of this method was determined to be 76% to 129% (n = 3), and both the interday (n = 6) and intraday (n = 7) precisions were less than 10%. The method was further applied for the quantifications of four adducts in the derma of adult male Sprague-Dawley rats exposed to SM ex vivo and in vivo, and all adducts had time- and dose-effect relationships. To the best of our knowledge, this is the first time that the real presented status of four DNA adducts was simultaneously revealed by the MS-based method, in which Bis-G showed much higher abundance than the result previously reported and N(3

Single-run determination of polybrominated diphenyl ethers (PBDEs) di- to deca-brominated in fish meal, fish oil and fish feed by isotope dilution: application of automated sample purification and gas chromatography/ion trap tandem mass spectrometry (GC/ITMS).

Science.gov (United States)

Blanco, Sonia Lucía; Vieites, Juan M

2010-07-05

The present paper describes the application of automated cleanup and fractionation procedures of the Power Prep system (Fluid Management Systems) for the determination of polybrominated diphenyl ethers (PBDEs) in feeding stuffs and fish meal and oil. Gas chromatography (GC) separation followed by ion trap tandem mass spectrometry detection in EI mode (ITMS) allowed the analysis of di- to deca-BDEs in the samples matrices used in fish aquaculture. The method developed enabled the determination of 26 native PBDE congeners and 11 (13)C(12)-labelled congeners, including deca-BDE 209, in a single-run analysis, using isotope dilution. The automated cleanup, consisting of a succession of multilayer silica and basic alumina columns previously applied by Wyrzykowska et al. (2009) [28] in combustion flue gas, was successfully applied in our complex matrices. The method allowed an increase in productivity, i.e. lower time was required to process samples, and simultaneous purification of several samples was achieved at a time, reducing analyst dedication and human error input. Average recoveries of 43-96% were obtained. GC/ITMS can overcome the complexity originating from the sample matrix, eliminating matrix effects by tandem MS, to enable the detection of congeners penta- to nona-BDEs where interferent masses were present. The provisional detection limits, estimated in the samples, were 5-30 pg for di-, tri-, tetra-, and penta-BDEs, 20-65 pg for hexa-, hepta-, octa- and nona-BDEs, and 105 pg for deca-BDE. Reduction of deca-BDE 209 blank values is of concern to ongoing research. Good accuracy was obtained by application of the whole procedure, representing an efficient, low-cost and fast alternative for routine analyses. Copyright 2010 Elsevier B.V. All rights reserved.

Measurement of Muscle Protein Fractional Synthetic Rate by Capillary Gas Chromatography/Combustion Isotope Ratio Mass Spectrometry

Science.gov (United States)

Yarasheski, Kevin E.; Smith, Kenneth; Rennie, Michael J.; Bier, Dennis M.

2014-01-01

The measurement of skeletal muscle protein fractional synthetic rate using an infusion of (1-13C)leucine and measuring the isotopic abundance of the tracer in skeletal muscle protein by preparative gas chromatography (GC)/ninhydrin isotope ratio mass spectrometry (IRMS) is laborious and subject to errors owing to contamination by 12C. The purpose of this study was to compare muscle (13C)leucine enrichment measured with the conventional preparative GC/ninhydrin IRMS approach to a new, continuous-flow technique using capillary GC/combustion IRMS. Quadriceps muscles were removed from four Sprague–Dawley rats after each was infused at a different rate with (1-13C)leucine for 6–8 h. Muscle leucine enrichment (at.% excess) measured by both methods differed by less than 4%, except at low (13C)leucine enrichments (IRMS was used to assess muscle (13C)leucine enrichment and fractional muscle protein synthesis rate in ten normal young men and women infused with (1,2-13C2)leucine for 12–14 h. This approach reduced the variability of the isotope abundance measure and gave estimates of muscle protein synthesis rate (0.050 ± 0.011% h−1 (mean ± SEM); range = 0.023–0.147% h−1) that agree with published values determined using the standard analytical approach. The measurement of (13C)leucine enrichment from skeletal muscle protein by capillary GC/combustion IRMS provides a simple, acceptable and practical alternative to preparative GC/ninhydrin IRMS. PMID:1420371

Ion Mobility Mass Spectrometry Direct Isotope Abundance Analysis

International Nuclear Information System (INIS)

Manard, Manuel J.; Weeks, Stephan; Kyle, Kevin

2010-01-01

The nuclear forensics community is currently engaged in the analysis of illicit nuclear or radioactive material for the purposes of non-proliferations and attribution. One technique commonly employed for gathering nuclear forensics information is isotope analysis. At present, the state-of-the-art methodology for obtaining isotopic distributions is thermal ionization mass spectrometry (TIMS). Although TIMS is highly accurate at determining isotope distributions, the technique requires an elementally pure sample to perform the measurement. The required radiochemical separations give rise to sample preparation times that can be in excess of one to two weeks. Clearly, the nuclear forensics community is in need of instrumentation and methods that can expedite their decision making process in the event of a radiological release or nuclear detonation. Accordingly, we are developing instrumentation that couples a high resolution IM drift cell to the front end of a MS. The IM cell provides a means of separating ions based upon their collision cross-section and mass-to-charge ratio (m/z). Two analytes with the same m/z, but with different collision cross-sections (shapes) would exit the cell at different times, essentially enabling the cell to function in a similar manner to a gas chromatography (GC) column. Thus, molecular and atomic isobaric interferences can be effectively removed from the ion beam. The mobility selected chemical species could then be introduced to a MS for high-resolution mass analysis to generate isotopic distributions of the target analytes. The outcome would be an IM/MS system capable of accurately measuring isotopic distributions while concurrently eliminating isobaric interferences and laboratory radiochemical sample preparation. The overall objective of this project is developing instrumentation and methods to produce near real-time isotope distributions with a modular mass spectrometric system that performs the required gas-phase chemistry and

Dilution Refrigeration of Multi-Ton Cold Masses

CERN Document Server

Wikus, P; CERN. Geneva

2007-01-01

Dilution refrigeration is the only means to provide continuous cooling at temperatures below 250 mK. Future experiments featuring multi-ton cold masses require a new generation of dilution refrigeration systems, capable of providing a heat sink below 10 mK at cooling powers which exceed the performance of present systems considerably. This thesis presents some advances towards dilution refrigeration of multi-ton masses in this temperature range. A new method using numerical simulation to predict the cooling power of a dilution refrigerator of a given design has been developed in the framework of this thesis project. This method does not only allow to take into account the differences between an actual and an ideal continuous heat exchanger, but also to quantify the impact of an additional heat load on an intermediate section of the dilute stream. In addition, transient behavior can be simulated. The numerical model has been experimentally verified with a dilution refrigeration system which has been designed, ...

Isotopic enrichment of 15N by ionic exchange chromatography

International Nuclear Information System (INIS)

Trivelin, P.C.O.

1979-01-01

The present paper presents some studies on production of 15 N-enriched ammonium sulphate with 5% atoms by ionic exchange chromatography method. Two systems are described of columns of resin, where experiments were conducted by eluition of NH 4 + bands with sodium hydroxide solution. Analyses were made of the cost of production of 15 N-enriched ammonium sulphate 5% atoms and, based on the experiments developed, a cost was obtained which was compatible with the international price of the product. The isotopic analyses of nitrogen were made by mass spectrometry. (Author) [pt

Stable isotope dilution HILIC-MS/MS method for accurate quantification of glutamic acid, glutamine, pyroglutamic acid, GABA and theanine in mouse brain tissues.

Science.gov (United States)

Inoue, Koichi; Miyazaki, Yasuto; Unno, Keiko; Min, Jun Zhe; Todoroki, Kenichiro; Toyo'oka, Toshimasa

2016-01-01

In this study, we developed the stable isotope dilution hydrophilic interaction liquid chromatography with tandem mass spectrometry (HILIC-MS/MS) technique for the accurate, reasonable and simultaneous quantification of glutamic acid (Glu), glutamine (Gln), pyroglutamic acid (pGlu), γ-aminobutyric acid (GABA) and theanine in mouse brain tissues. The quantification of these analytes was accomplished using stable isotope internal standards and the HILIC separating mode to fully correct the intramolecular cyclization during the electrospray ionization. It was shown that linear calibrations were available with high coefficients of correlation (r(2)  > 0.999, range from 10 pmol/mL to 50 mol/mL). For application of the theanine intake, the determination of Glu, Gln, pGlu, GABA and theanine in the hippocampus and central cortex tissues was performed based on our developed method. In the region of the hippocampus, the concentration levels of Glu and pGlu were significantly reduced during reality-based theanine intake. Conversely, the concentration level of GABA increased. This result showed that transited theanine has an effect on the metabolic balance of Glu analogs in the hippocampus. Copyright © 2015 John Wiley & Sons, Ltd.

Quantification of Labile Soil Mercury by Stable Isotope Dilution Techniques

Science.gov (United States)

Shetaya, Waleed; Huang, Jen-How; Osterwalder, Stefan; Alewell, Christine

2016-04-01

Mercury (Hg) is a toxic element that can cause severe health problems to humans. Mercury is emitted to the atmosphere from both natural and anthropogenic sources and can be transported over long distances before it is deposited to aquatic and terrestrial environments. Aside from accumulation in soil solid phases, Hg deposited in soils may migrate to surface- and ground-water or enter the food chain, depending on its lability. There are many operationally-defined extraction methods proposed to quantify soil labile metals. However, these methods are by definition prone to inaccuracies such as non-selectivity, underestimation or overestimation of the labile metal pool. The isotopic dilution technique (ID) is currently the most promising method for discrimination between labile and non-labile metal fractions in soil with a minimum disturbance to soil-solid phases. ID assesses the reactive metal pool in soil by defining the fraction of metal both in solid and solution phases that is isotopically-exchangeable known as the 'E-value'. The 'E-value' represents the metal fraction in a dynamic equilibrium with the solution phase and is potentially accessible to plants. This is carried out by addition of an enriched metal isotope to soil suspensions and quantifying the fraction of metal that is able to freely exchange with the added isotope by measuring the equilibrium isotopic ratio by ICP-MS. E-value (mg kg-1) is then calculated as follows: E-Value = (Msoil/ W) (CspikeVspike/ Mspike) (Iso1IAspike -Iso2IAspikeRss / Iso2IAsoil Rss - Iso1IAsoil) where M is the average atomic mass of the metal in the soil or the spike, W is the mass of soil (kg), Cspike is the concentration of the metal in the spike (mg L-1), Vspike is the volume of spike (L), IA is isotopic abundance, and Rss is the equilibrium ratio of isotopic abundances (Iso1:Iso2). Isotopic dilution has been successfully applied to determine E-values for several elements. However, to our knowledge, this method has not yet

Isotope dilution mass spectrometry as the primary method of measurement for the amount of matter. Application to cadmium determination in biological materials and comparison with instrumental neutron activation analysis

International Nuclear Information System (INIS)

Munoz, Luis; Gras, Nuri; Quejido, Alberto; Ferrada, Carlos

2001-01-01

A primary method of measurement as defined by the Consultative Committee on the Quantity of Matter (Comite Consultatif pour la Quantite de Matiere, CCQM) of the International Bureau of Weights and Measurements (Bureau International des Poids et Mesures, BIPM), is one whose measurement process is perfectly known, has valid theoretical foundations and is fully described and answers to an equation that relates what is measured with what is intended to be measured without any significant empirical correction factors. It is also a method that has insignificant systematic errors, where only magnitudes from the International System of Units (SI) are used and where, preferably, the uncertainties are small ones. They are, therefore, procedures that do not need instrumental calibration. The absolute methods of measurement allow a chain of traceability to be formed between the result obtained and the magnitude of the SI assigned to what is measured. So the results are said to be traceable to the SI. One of the methods that meets these requirements and is recognized as the primary method by the CCQM is Isotope Dilution Mass Spectrometry (IDMS). Through a project of Technical Cooperation with the International Atomic Energy Agency in the area of Chemical Metrology, the CCHEN obtained training in CIEMAT, Spain, in IDMS and its applications to the analysis of biological samples. This work describes the first experience carried out entirely in Chilean laboratories, applying IDMS to the determination of cadmium in the biological reference materials Oyster Tissue 15566-A from the NIST, United States, Dogfish Liver, DOLT-2 from the NRC-CNRC, Canada and Poplar Leaves GBW07604 from the NRCC, China. The samples were traced with an isotope enriched spike 111 Cd and then shaken to obtain the isotopic exchange. Once dissolved, the isotopic relationship 111 Cd/ 114 Cd was determined in the samples using mass spectrometry with plasma source. These results were compared with those obtained

Quantitative determination of cyclobutane thymine dimers in DNA by stable isotope-dilution mass spectrometry

International Nuclear Information System (INIS)

Podmore, I.D.; Cooke, M.S.; Herbert, K.E.; Lunec, J.

1996-01-01

In order to understand the role of UV-induced DNA lesions in biological processes such as mutagenesis and carcinogenesis, it is essential to detect and quantify DNA damage in cells. In this paper we present a novel and both highly selective and sensitive assay using capillary gas chromatography (GC) combined with mass spectrometry (MS) for the detection and accurate quantitation of a major product of UV-induced DNA damage (cis-syb cyclobutadithymine). Quantitation of the cyclobutane thymine dimer was achieved by the use of an internal standard in the form of a stable 2 H-labeled analogue. Both isotopically labeled and nonlabeled dimers were prepared directly from their corresponding monomers. Each was identified as their trimethylsilyl ether derivative by GC-MS. Calibration plots were obtained for known quantities of both nonlabeled and analyte and internal standard. Quantitation of cis-syn cyclobutadithymine was demonstrated in DNA exposed to UVC radiation over a dose range of 0 3500 J m -2 . Under the conditions used, the limit of detection was found to be 20-50 fmol on column (equivalent to 0.002-0.005 nmol dimer per mg DNA). The results of the present study indicate that capillary GC-MS is an ideally suited technique for selective and sensitive quantification of cis-syn cyclobutadithymine in DNA and hence UV-induced DNA damage. (author)

Optimization of an online heart-cutting multidimensional gas chromatography clean-up step for isotopic ratio mass spectrometry and simultaneous quadrupole mass spectrometry measurements of endogenous anabolic steroid in urine.

Science.gov (United States)

Casilli, Alessandro; Piper, Thomas; de Oliveira, Fábio Azamor; Padilha, Monica Costa; Pereira, Henrique Marcelo; Thevis, Mario; de Aquino Neto, Francisco Radler

2016-11-01

Measuring carbon isotope ratios (CIRs) of urinary analytes represents a cornerstone of doping control analysis and has been particularly optimized for the detection of the misuse of endogenous steroids. Isotope ratio mass spectrometry (IRMS) of appropriate quality, however, necessitates adequate purities of the investigated steroids, which requires extensive pre-analytical sample clean-up steps due to both the natural presence of the target analytes and the high complexity of the matrix. In order to accelerate the sample preparation and increase the automation of the process, the use of multidimensional gas chromatography (MDGC) prior to IRMS experiments, was investigated. A well-established instrumental configuration based on two independent GC ovens and one heart-cutting device was optimized. The first dimension (1D) separation was obtained by a non-polar column which assured high efficiency and good loading capacity, while the second dimension (2D), based on a mid-polar stationary phase, provided good selectivity. A flame ionization detector monitored the 1D, and the 2D was simultaneously recorded by isotope ratio and quadrupole mass spectrometry. The assembled MDGC set-up was applied for measuring testosterone, 5α- and 5β-androstanediol, androsterone, and etiocholanolone as target compounds and pregnanediol as endogenous reference compound. The urine sample were pretreated by conventional sample preparation steps comprising solid-phase extraction, hydrolysis, and liquid-liquid extraction. The extract obtained was acetylated and different aliquots were injected into the MDGC system. Two high performance liquid chromatography steps, conventionally adopted prior to CIR measurements, were replaced by the MDGC approach. The obtained values were consistent with the conventional ones. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Introducing AAA-MS, a rapid and sensitive method for amino acid analysis using isotope dilution and high-resolution mass spectrometry.

Science.gov (United States)

Louwagie, Mathilde; Kieffer-Jaquinod, Sylvie; Dupierris, Véronique; Couté, Yohann; Bruley, Christophe; Garin, Jérôme; Dupuis, Alain; Jaquinod, Michel; Brun, Virginie

2012-07-06

Accurate quantification of pure peptides and proteins is essential for biotechnology, clinical chemistry, proteomics, and systems biology. The reference method to quantify peptides and proteins is amino acid analysis (AAA). This consists of an acidic hydrolysis followed by chromatographic separation and spectrophotometric detection of amino acids. Although widely used, this method displays some limitations, in particular the need for large amounts of starting material. Driven by the need to quantify isotope-dilution standards used for absolute quantitative proteomics, particularly stable isotope-labeled (SIL) peptides and PSAQ proteins, we developed a new AAA assay (AAA-MS). This method requires neither derivatization nor chromatographic separation of amino acids. It is based on rapid microwave-assisted acidic hydrolysis followed by high-resolution mass spectrometry analysis of amino acids. Quantification is performed by comparing MS signals from labeled amino acids (SIL peptide- and PSAQ-derived) with those of unlabeled amino acids originating from co-hydrolyzed NIST standard reference materials. For both SIL peptides and PSAQ standards, AAA-MS quantification results were consistent with classical AAA measurements. Compared to AAA assay, AAA-MS was much faster and was 100-fold more sensitive for peptide and protein quantification. Finally, thanks to the development of a labeled protein standard, we also extended AAA-MS analysis to the quantification of unlabeled proteins.

Rapid Determination of Plutonium Isotopes in Environmental Samples Using Sequential Injection Extraction Chromatography and Detection by Inductively Coupled Plasma Mass Spectrometry

DEFF Research Database (Denmark)

Qiao, Jixin; Hou, Xiaolin; Roos, Per

2009-01-01

This article presents an automated method for the rapid determination of 239Pu and 240Pu in various environmental samples. The analytical method involves the in-line separation of Pu isotopes using extraction chromatography (TEVA) implemented in a sequential injection (SI) network followed...... by detection of isolated analytes with inductively coupled plasma mass spectrometry (ICP-MS). The method has been devised for the determination of Pu isotopes at environmentally relevant concentrations, whereby it has been successfully applied to the analyses of large volumes/amounts of samples, for example......, 100−200 g of soil and sediment, 20 g of seaweed, and 200 L of seawater following analyte preconcentration. The investigation of the separation capability of the assembled SI system revealed that up to 200 g of soil or sediment can be treated using a column containing about 0.70 g of TEVA resin...

Comparison of bile acid synthesis determined by isotope dilution versus fecal acidic sterol output in human subjects

International Nuclear Information System (INIS)

Duane, W.C.; Holloway, D.E.; Hutton, S.W.; Corcoran, P.J.; Haas, N.A.

1982-01-01

Fecal acidic sterol output has been found to be much lower than bile acid synthesis determined by isotope dilution. Because of this confusing discrepancy, we compared these 2 measurements done simultaneously on 13 occasions in 5 normal volunteers. In contrast to previous findings, bile acid synthesis by the Lindstedt isotope dilution method averaged 16.3% lower than synthesis simultaneously determined by fecal acidic sterol output (95% confidence limit for the difference - 22.2 to -10.4%). When one-sample determinations of bile acid pools were substituted for Lindstedt pools, bile acid synthesis by isotope dilution averaged 5.6% higher than synthesis by fecal acidic sterol output (95% confidence limits -4.9 to 16.1%). These data indicate that the 2 methods yield values in reasonably close agreement with one another. If anything, fecal acidic sterol outputs are slightly higher than synthesis by isotope dilution

Effects of Conventional Heating on the Stability of Major Olive Oil Phenolic Compounds by Tandem Mass Spectrometry and Isotope Dilution Assay

Directory of Open Access Journals (Sweden)

Giovanni Sindona

2010-12-01

Full Text Available The quality of olive oils is sensorially tested by accurate and well established methods. It enables the classification of the pressed oils into the classes of extra virgin oil, virgin oil and lampant oil. Nonetheless, it would be convenient to have analytical methods for screening oils or supporting sensorial analysis using a reliable independent approach based on exploitation of mass spectrometric methodologies. A number of methods have been proposed to evaluate deficiencies of extra virgin olive oils resulting from inappropriate technological treatments, such as high or low temperature deodoration, and home cooking processes. The quality and nutraceutical value of extra virgin olive oil (EVOO can be related to the antioxidant property of its phenolic compounds. Olive oil is a source of at least 30 phenolic compounds, such as oleuropein, oleocanthal, hydroxytyrosol, and tyrosol, all acting as strong antioxidants, radical scavengers and NSAI-like drugs. We now report the efficacy of MRM tandem mass spectrometry, assisted by the isotope dilution assay, in the evaluation of the thermal stability of selected active principles of extra virgin olive oil.

Effects of conventional heating on the stability of major olive oil phenolic compounds by tandem mass spectrometry and isotope dilution assay.

Science.gov (United States)

Attya, Mohamed; Benabdelkamel, Hicham; Perri, Enzo; Russo, Anna; Sindona, Giovanni

2010-12-01

The quality of olive oils is sensorially tested by accurate and well established methods. It enables the classification of the pressed oils into the classes of extra virgin oil, virgin oil and lampant oil. Nonetheless, it would be convenient to have analytical methods for screening oils or supporting sensorial analysis using a reliable independent approach based on exploitation of mass spectrometric methodologies. A number of methods have been proposed to evaluate deficiencies of extra virgin olive oils resulting from inappropriate technological treatments, such as high or low temperature deodoration, and home cooking processes. The quality and nutraceutical value of extra virgin olive oil (EVOO) can be related to the antioxidant property of its phenolic compounds. Olive oil is a source of at least 30 phenolic compounds, such as oleuropein, oleocanthal, hydroxytyrosol, and tyrosol, all acting as strong antioxidants, radical scavengers and NSAI-like drugs. We now report the efficacy of MRM tandem mass spectrometry, assisted by the isotope dilution assay, in the evaluation of the thermal stability of selected active principles of extra virgin olive oil.

Separation of boron isotopes by ion exchange chromatography: studies on regeneration of strong base anion exchange resins

International Nuclear Information System (INIS)

Sharma, B.K.; Subramanian, R.; Mathur, P.K.

1994-01-01

The optimum conditions for the regeneration of strong base anion exchange resins of type-I and type-II were determined for cost-effective separation of isotopes of boron by ion exchange chromatography where the hydroxyl form of an anion exchange resin is equilibrated with boric acid solution containing mannitol as a complexing reagent. The possibility of using unspent alkali content of the effluent was also exploited. Removal of carbonate impurity from Rayon grade caustic lye (used as regenerant after dilution) and recycling of Ba(OH) 2 was studied to avoid waste disposal problems. (author)

Detection of Stimulants and Narcotics by Liquid Chromatography-Tandem Mass Spectrometry and Gas Chromatography-Mass Spectrometry for Sports Doping Control.

Science.gov (United States)

Ahrens, Brian D; Kucherova, Yulia; Butch, Anthony W

2016-01-01

Sports drug testing laboratories are required to detect several classes of compounds that are prohibited at all times, which include anabolic agents, peptide hormones, growth factors, beta-2 agonists, hormones and metabolic modulators, and diuretics/masking agents. Other classes of compounds such as stimulants, narcotics, cannabinoids, and glucocorticoids are also prohibited, but only when an athlete is in competition. A single class of compounds can contain a large number of prohibited substances and all of the compounds should be detected by the testing procedure. Since there are almost 70 stimulants on the prohibited list it can be a challenge to develop a single screening method that will optimally detect all the compounds. We describe a combined liquid chromatography-tandem mass spectrometry (LC-MS/MS) and gas chromatography-mass spectrometry (GC-MS) testing method for detection of all the stimulants and narcotics on the World Anti-Doping Agency prohibited list. Urine for LC-MS/MS testing does not require sample pretreatment and is a direct dilute and shoot method. Urine samples for the GC-MS method require a liquid-liquid extraction followed by derivatization with trifluoroacetic anhydride.

Simultaneous determination of 11 β-agonists in human urine using high-performance liquid chromatography/tandem mass spectrometry with isotope dilution.

Science.gov (United States)

Wang, Xiaoli; Guo, Tao; Wang, Shanshan; Yuan, Jinpeng; Zhao, Rusong

2015-04-01

The misuse of β-agonists constitutes a potential risk to public health and has been forbidden in many countries. In this study, we describe a method for specific, sensitive and rapid detection of β-agonists in human urine. Urine samples were extracted with ethyl acetate, without any additional purification step, and analyzed by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS-MS) with Clenbuterol-D9 and Salbuterol-D3 as internal standards. The intra- and interday precision values of the method were all application of UPLC-MS-MS method in β-agonists detection of human urine will be helpful in veterinary control of β-agonists and for studying the effect of β-agonists on human health. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Mercury speciation analysis in seafood by species-specific isotope dilution: method validation and occurrence data

Energy Technology Data Exchange (ETDEWEB)

Clemens, Stephanie; Guerin, Thierry [Agence Nationale de Securite Sanitaire de l' Alimentation, Laboratoire de Securite des Aliments de Maisons-Alfort, Unite des Contaminants Inorganiques et Mineraux de l' Environnement, ANSES, Maisons-Alfort (France); Monperrus, Mathilde; Donard, Olivier F.X.; Amouroux, David [IPREM UMR 5254 CNRS - Universite de Pau et des Pays de l' Adour, Laboratoire de Chimie Analytique Bio-Inorganique et Environnement, Institut des Sciences Analytiques et de Physico-chimie pour l' Environnement et les Materiaux, Pau Cedex (France)

2011-11-15

Methylmercury (MeHg) and total mercury (THg) in seafood were determined using species-specific isotope dilution analysis and gas chromatography combined with inductively coupled plasma mass spectrometry. Sample preparation methods (extraction and derivation step) were evaluated on certified reference materials using isotopically enriched Hg species. Solid-liquid extraction, derivation by propylation and automated agitation gave excellent accuracy and precision results. Satisfactory figures of merit for the selected method were obtained in terms of limit of quantification (1.2 {mu}g Hg kg{sup -1} for MeHg and 1.4 {mu}g Hg kg{sup -1} for THg), repeatability (1.3-1.7%), intermediate precision reproducibility (1.5% for MeHg and 2.2% for THg) and trueness (bias error less than 7%). By means of a recent strategy based on accuracy profiles ({beta}-expectation tolerance intervals), the selected method was successfully validated in the range of approximately 0.15-5.1 mg kg{sup -1} for MeHg and 0.27-5.2 mg kg{sup -1} for THg. Probability {beta} was set to 95% and the acceptability limits to {+-}15%. The method was then applied to 62 seafood samples representative of consumption in the French population. The MeHg concentrations were generally low (1.9-588 {mu}g kg{sup -1}), and the percentage of MeHg varied from 28% to 98% in shellfish and from 84% to 97% in fish. For all real samples tested, methylation and demethylation reactions were not significant, except in one oyster sample. The method presented here could be used for monitoring food contamination by MeHg and inorganic Hg in the future to more accurately assess human exposure. (orig.)

Glucose and glycerol concentrations and their tracer enrichment measurements using liquid chromatography tandem mass spectrometry

DEFF Research Database (Denmark)

Bornø, Andreas; Foged, Lene; van Hall, Gerrit

2014-01-01

The present study describes a new liquid chromatography tandem mass spectrometry method for high-throughput quantification of glucose and glycerol in human plasma using stable isotopically labeled internal standards and is suitable for simultaneous measurements of glucose and glycerol enrichments...... of variation were 2.0% and 9.7%, respectively. After derivatization, plasma samples were stable for at least 14 days. In conclusion, we have developed and validated a novel, accurate, and sensitive high-throughput liquid chromatography tandem mass spectrometry method for simultaneous determination of glucose...

Simple and accurate measurement of carbamazepine in surface water by use of porous membrane-protected micro-solid-phase extraction coupled with isotope dilution mass spectrometry

Energy Technology Data Exchange (ETDEWEB)

Teo, Hui Ling [Chemical Metrology Division, Applied Sciences Group, Health Sciences Authority, 1 Science Park Road, #01-05/06, The Capricorn, Singapore Science Park II, Singapore 117528 (Singapore); Department of Chemistry, National University of Singapore, 3 Science Drive 3, Singapore 117543 (Singapore); Wong, Lingkai [Chemical Metrology Division, Applied Sciences Group, Health Sciences Authority, 1 Science Park Road, #01-05/06, The Capricorn, Singapore Science Park II, Singapore 117528 (Singapore); Liu, Qinde, E-mail: liu_qinde@hsa.gov.sg [Chemical Metrology Division, Applied Sciences Group, Health Sciences Authority, 1 Science Park Road, #01-05/06, The Capricorn, Singapore Science Park II, Singapore 117528 (Singapore); Teo, Tang Lin; Lee, Tong Kooi [Chemical Metrology Division, Applied Sciences Group, Health Sciences Authority, 1 Science Park Road, #01-05/06, The Capricorn, Singapore Science Park II, Singapore 117528 (Singapore); Lee, Hian Kee, E-mail: chmleehk@nus.edu.sg [Department of Chemistry, National University of Singapore, 3 Science Drive 3, Singapore 117543 (Singapore)

2016-03-17

To achieve fast and accurate analysis of carbamazepine in surface water, we developed a novel porous membrane-protected micro-solid-phase extraction (μ-SPE) method, followed by liquid chromatography-isotope dilution tandem mass spectrometry (LC-IDMS/MS) analysis. The μ-SPE device (∼0.8 × 1 cm) was fabricated by heat-sealing edges of a polypropylene membrane sheet to devise a bag enclosing the sorbent. The analytes (both carbamazepine and isotope-labelled carbamazepine) were first extracted by μ-SPE device in the sample (10 mL) via agitation, then desorbed in an organic solvent (1 mL) via ultrasonication. Several parameters such as organic solvent for pre-conditioning of μ-SPE device, amount of sorbent, adsorption time, and desorption solvent and time were investigated to optimize the μ-SPE efficiency. The optimized method has limits of detection and quantitation estimated to be 0.5 ng L{sup −1} and 1.6 ng L{sup −1}, respectively. Surface water samples spiked with different amounts of carbamazepine (close to 20, 500, and 1600 ng L{sup −1}, respectively) were analysed for the validation of method precision and accuracy. Good precision was obtained as demonstrated by relative standard deviations of 0.7% for the samples with concentrations of 500 and 1600 ng kg{sup −1}, and 5.8% for the sample with concentration of 20 ng kg{sup −1}. Good accuracy was also demonstrated by the relative recoveries in the range of 96.7%–103.5% for all samples with uncertainties of 1.1%–5.4%. Owing to the same chemical properties of carbamazepine and isotope-labelled carbamazepine, the isotope ratio in the μ-SPE procedure was accurately controlled. The use of μ-SPE coupled with IDMS analysis significantly facilitated the fast and accurate measurement of carbamazepine in surface water. - Highlights: • μ-SPE coupled with IDMS for the measurement of carbamazepine. • The method is the first report of coupling μ-SPE with IDMS. • μ-SPE is fast, time

The research of sub-picogram plutonium's quantitative analysis by isotope mass spectrometry

International Nuclear Information System (INIS)

Tang Lei; Long Kaiming; Yang Tianli; Liu Xuemei

2005-10-01

By using active carbon powder as emission matter, the detect sensitivity of 239 Pu was 0.5 pg (1 ± 0.15, 95% confidence level), improved 20 times compared with the sensitivity 10 pg (1 ± 0.5) of the tradition method. The sub-picogram plutonium sample was determined quantatively by isotope dilution mass spectrometry (IDMS). (authors)

On-line monitoring of benzene air concentrations while driving in traffic by means of isotopic dilution gas chromatography/mass spectrometry.

Science.gov (United States)

Davoli, E; Cappellini, L; Moggi, M; Ferrari, S; Fanelli, R

1996-01-01

There is no shortage of information about the average benzene concentrations in urban air, but there is very little about microenvironmental exposure, such as in-vehicle concentrations while driving in various traffic conditions, while refuelling, or while in a parking garage. The main reason for this lack of data is that no analytical instrumentation has been available to measure on-line trace amounts of benzene in such situations. We have recently proposed a highly accurate, high-speed cryofocusing gas chromatography/mass spectrometry (GC/MS) system for monitoring benzene concentrations in air. Accuracy of the analytical data is achieved by enrichment of the air sample before trapping, with a stable isotope permeation tube system. The same principles have been applied to a new instrument, specifically designed for operation on an electric vehicle (Ducato Elettra, Fiat). The zero emission vehicle and the fully transportable, battery-operated GC/MS system provide a unique possibility of monitoring benzene exposure in real everyday situations such as while driving, refuelling, or repairing a car. All power consumptions have been reduced so as to achieve a battery-operated GC/MS system. Liquid nitrogen cryofocusing has been replaced by a packed, inductively heated, graphitized charcoal microtrap. The instrument has been mounted on shock absorbers and installed in the van. The whole system has been tested in both fixed and mobile conditions. The maximum monitoring period without external power supply is 6 h. The full analytical cycle is 4 min, allowing close to real-time monitoring, and the minimum detectable level is 1 microgram/m3 for benzene. In-vehicle monitoring showed that, when recirculation was off and ventilation on, i.e., air from outside the vehicle was blown inside, concentrations varied widely in different driving conditions: moving from a parking lot into normal traffic on an urban traffic condition roadway yielded an increase in benzene concentration

Gas chromatography and isotope ratio mass spectrometry of Pinot Noir wine volatile compounds (δ13C) and solid residues (δ13C, δ15N) for the reassessment of vineyard water-status.

Science.gov (United States)

Spangenberg, Jorge E; Vogiatzaki, Maria; Zufferey, Vivian

2017-09-29

This paper describes a novel approach to reassess the water status in vineyards based on compound-specific isotope analysis (CSIA) of wine volatile organic compounds (δ 13 C VOC/VPDB ) and bulk carbon and nitrogen isotopes, and the C/N molar ratios of the wine solid residues (δ 13 C SR/VPDB , δ 15 N SR/Air-N2 ). These analyses link gas chromatography/combustion and elemental analysis to isotope ratio mass spectrometry (GC/C/IRMS, EA/IRMS). Field-grown cultivars of Pinot Noir grapevines were exposed during six growing seasons (2009-2014) to controlled soil water availability, while maintaining identical the other environmental variables and agricultural techniques. Wines were produced from the grapes by the same oenological protocol. This permitted for the assessment of the effects in the biochemistry of wines solely induced by the changes in the plant-soil water status. This mimicked the more recurrent and prolonged periods of soil water deficiency due to climate changes. Water stress in grapevine was assessed by the measurement of the predawn leaf water potential (Ψ pd ) and the stable carbon isotope composition of the berry sugars during harvest (must sugars). For quantitation purposes and the normalization of the measured stable carbon isotope ratios of the VOCs, the wine samples were spiked with three standard compounds with known concentration and δ 13 C VPDB values. VOCs were extracted by liquid-liquid extraction and analyzed by gas chromatography/flame ionization detection (GC/FID), gas chromatography/mass spectrometry (GC/MS), and GC/C/IRMS. δ 13 C values were obtained for eighteen VOCs. The solid residues were obtained by freeze-drying wine aliquots and were analyzed for their C and N content and isotope composition by EA/IRMS. All the isotopic ratios (δ 13 C SR , δ 15 N SR , δ 13 C VOC ) are highly correlated with the Ψ pd values, indicating that the proposed gas chromatography and isotope ratio mass spectrometry approach is a useful tool to

Method development for the determination of cadmium, copper, lead, selenium and thallium in sediments by slurry sampling electrothermal vaporization inductively coupled plasma mass spectrometry and isotopic dilution calibration

International Nuclear Information System (INIS)

Dias, Lucia Felicidade; Miranda, Gilson R.; Saint'Pierre, Tatiana D.; Maia, Sandra M.; Frescura, Vera L.A.; Curtius, Adilson J.

2005-01-01

A procedure for the determination of Cd, Cu, Pb, Se and Tl by slurry sampling electrothermal vaporization inductively coupled plasma mass spectrometry (ETV-ICP-MS) with calibration by isotopic dilution is proposed. The slurry is prepared by mixing the sample with diluted nitric and hydrofluoric acids in an ultrasonic bath and then in a water bath at 60 deg C for 120 min. The slurries were let to stand at least for 12 h, manually shaken before poured into the autosampler cups and homogenized by passing through an argon flow, just before pipetting it into the furnace. The analytes were determined in two groups, according to their thermal behaviors. The furnace temperature program was optimized and the selected compromised pyrolysis temperatures were: 400 deg C for Cd, Se and Tl and 700 deg C for Cu and Pb. The vaporization temperature was 2300 deg C. The analyses were carried out without modifier as no significant effect was observed for different tested modifiers. Different sample particle sizes did not affect the sensitivity significantly, then a particle size ≤50 μm was adopted. The accuracy was checked by analyzing five certified reference sediments, with analytes concentrations from sub-μg g -1 to a few hundreds μg g -1 . The great majority of the obtained concentrations were in agreement with the certified values. The detection limits, determined for the MESS-2 certified sediment, were, in μg g -1 : 0.01 for Cd; 0.8 for Cu; 0.4 for Pb; 0.4 for Se and 0.06 for Tl. The precision was adequate with relative standard deviations lower than 12%. Isotopic dilution showed to be an efficient calibration technique for slurry, as the extraction of the analyte to the liquid phase of the slurry and the reactions in the vaporizer must help the equilibration between the added isotope and the isotope in the sample

Quantification of Stable Isotope Traces Close to Natural Enrichment in Human Plasma Metabolites Using Gas Chromatography-Mass Spectrometry.

Science.gov (United States)

Krämer, Lisa; Jäger, Christian; Trezzi, Jean-Pierre; Jacobs, Doris M; Hiller, Karsten

2018-02-14

Currently, changes in metabolic fluxes following consumption of stable isotope-enriched foods are usually limited to the analysis of postprandial kinetics of glucose. Kinetic information on a larger diversity of metabolites is often lacking, mainly due to the marginal percentage of fully isotopically enriched plant material in the administered food product, and hence, an even weaker 13 C enrichment in downstream plasma metabolites. Therefore, we developed an analytical workflow to determine weak 13 C enrichments of diverse plasma metabolites with conventional gas chromatography-mass spectrometry (GC-MS). The limit of quantification was increased by optimizing (1) the metabolite extraction from plasma, (2) the GC-MS measurement, and (3) most importantly, the computational data processing. We applied our workflow to study the catabolic dynamics of 13 C-enriched wheat bread in three human subjects. For that purpose, we collected time-resolved human plasma samples at 16 timepoints after the consumption of 13 C-labeled bread and quantified 13 C enrichment of 12 metabolites (glucose, lactate, alanine, glycine, serine, citrate, glutamate, glutamine, valine, isoleucine, tyrosine, and threonine). Based on isotopomer specific analysis, we were able to distinguish catabolic profiles of starch and protein hydrolysis. More generally, our study highlights that conventional GC-MS equipment is sufficient to detect isotope traces below 1% if an appropriate data processing is integrated.

Quantification of Stable Isotope Traces Close to Natural Enrichment in Human Plasma Metabolites Using Gas Chromatography-Mass Spectrometry

Science.gov (United States)

Krämer, Lisa; Jäger, Christian; Jacobs, Doris M.; Hiller, Karsten

2018-01-01

Currently, changes in metabolic fluxes following consumption of stable isotope-enriched foods are usually limited to the analysis of postprandial kinetics of glucose. Kinetic information on a larger diversity of metabolites is often lacking, mainly due to the marginal percentage of fully isotopically enriched plant material in the administered food product, and hence, an even weaker 13C enrichment in downstream plasma metabolites. Therefore, we developed an analytical workflow to determine weak 13C enrichments of diverse plasma metabolites with conventional gas chromatography-mass spectrometry (GC-MS). The limit of quantification was increased by optimizing (1) the metabolite extraction from plasma, (2) the GC-MS measurement, and (3) most importantly, the computational data processing. We applied our workflow to study the catabolic dynamics of 13C-enriched wheat bread in three human subjects. For that purpose, we collected time-resolved human plasma samples at 16 timepoints after the consumption of 13C-labeled bread and quantified 13C enrichment of 12 metabolites (glucose, lactate, alanine, glycine, serine, citrate, glutamate, glutamine, valine, isoleucine, tyrosine, and threonine). Based on isotopomer specific analysis, we were able to distinguish catabolic profiles of starch and protein hydrolysis. More generally, our study highlights that conventional GC-MS equipment is sufficient to detect isotope traces below 1% if an appropriate data processing is integrated. PMID:29443915

Quantification of Stable Isotope Traces Close to Natural Enrichment in Human Plasma Metabolites Using Gas Chromatography-Mass Spectrometry

Directory of Open Access Journals (Sweden)

Lisa Krämer

2018-02-01

Full Text Available Currently, changes in metabolic fluxes following consumption of stable isotope-enriched foods are usually limited to the analysis of postprandial kinetics of glucose. Kinetic information on a larger diversity of metabolites is often lacking, mainly due to the marginal percentage of fully isotopically enriched plant material in the administered food product, and hence, an even weaker 13C enrichment in downstream plasma metabolites. Therefore, we developed an analytical workflow to determine weak 13C enrichments of diverse plasma metabolites with conventional gas chromatography-mass spectrometry (GC-MS. The limit of quantification was increased by optimizing (1 the metabolite extraction from plasma, (2 the GC-MS measurement, and (3 most importantly, the computational data processing. We applied our workflow to study the catabolic dynamics of 13C-enriched wheat bread in three human subjects. For that purpose, we collected time-resolved human plasma samples at 16 timepoints after the consumption of 13C-labeled bread and quantified 13C enrichment of 12 metabolites (glucose, lactate, alanine, glycine, serine, citrate, glutamate, glutamine, valine, isoleucine, tyrosine, and threonine. Based on isotopomer specific analysis, we were able to distinguish catabolic profiles of starch and protein hydrolysis. More generally, our study highlights that conventional GC-MS equipment is sufficient to detect isotope traces below 1% if an appropriate data processing is integrated.

Isotope dilution inductively coupled plasma quadrupole mass spectrometry in connection with a chromatographic separation for ultra trace determinations of platinum group elements (Pt, Pd, Ru, Ir) in environmental samples.

Science.gov (United States)

Müller, M; Heumann, K G

2000-09-01

An isotope dilution inductively coupled plasma quadrupole mass spectrometric (ID-ICP-QMS) method was developed for the simultaneous determination of the platinum group elements Pt, Pd, Ru, and Ir in environmental samples. Spike solutions, enriched with the isotopes 194Pt, 108Pd, 99Ru, and 191Ir, were used for the isotope dilution step. Interfering elements were eliminated by chromatographic separation using an anion-exchange resin. Samples were dissolved with aqua regia in a high pressure asher. Additional dissolution of possible silicate portions by hydrofluoric acid was usually not necessary. Detection limits of 0.15 ng x g(-1), 0.075 ng x g(-1), and 0.015 ng x g(-1) were achieved for Pt, Pd, Ru, and Ir, respectively, using sample weights of only 0.2 g. The reliability of the ID-ICP-QMS method was demonstrated by analyzing a Canadian geological reference material and by participating in an interlaboratory study for the determination of platinum and palladium in a homogenized road dust sample. Surface soil, sampled at different distances from a highway, showed concentrations in the range of 0.1-87 ng x g(-1). An exponential decrease of the platinum and palladium concentration with increasing distance and a small anthropogenic contribution to the natural background concentration of ruthenium and iridium was found in these samples.

Quantitating subcellular metabolism with multi-isotope imaging mass spectrometry

Science.gov (United States)

Steinhauser, Matthew L.; Bailey, Andrew; Senyo, Samuel E.; Guillermier, Christelle; Perlstein, Todd S.; Gould, Alex P.; Lee, Richard T.; Lechene, Claude P.

2011-01-01

Mass spectrometry with stable isotope labels has been seminal in discovering the dynamic state of living matter1,2 but is limited to bulk tissues or cells. We developed multi-isotope imaging mass spectrometry (MIMS) that allowed us to view and measure stable isotope incorporation with sub-micron resolution3,4. Here we apply MIMS to diverse organisms, including Drosophila, mice, and humans. We test the “immortal strand hypothesis,” which predicts that during asymmetric stem cell division chromosomes containing older template DNA are segregated to the daughter destined to remain a stem cell, thus insuring lifetime genetic stability. After labeling mice with 15N-thymidine from gestation through post-natal week 8, we find no 15N label retention by dividing small intestinal crypt cells after 4wk chase. In adult mice administered 15N-thymidine pulse-chase, we find that proliferating crypt cells dilute label consistent with random strand segregation. We demonstrate the broad utility of MIMS with proof-of-principle studies of lipid turnover in Drosophila and translation to the human hematopoietic system. These studies show that MIMS provides high-resolution quantitation of stable isotope labels that cannot be obtained using other techniques and that is broadly applicable to biological and medical research. PMID:22246326

ICP-MS as the method of the determination of gallium, indium and thallium isotope ratios in the studies of isotope effects in the chromatography systems

International Nuclear Information System (INIS)

Herdzik, I.

2006-01-01

The procedure of the determination of gallium, indium and thallium isotope ratios and its application to the studies of the isotope effects in chromatography systems by the ICP-MS method (inductively coupled plasma-mass spectrometry) are presented. It was shown that it is possible to determine the isotope ratios of gallium ( 69/71 Ga), indium ( 113/115 In) and thallium ( 203/205 Tl) with the relative standard deviation 0.03-0.07%. Such precision appeared to be sufficient to calculate the unit separation factors in the column chromatographic processes. (author) [pl

Magnesium isotope fractionation in cation-exchange chromatography

International Nuclear Information System (INIS)

Oi, T.; Yanase, S.; Kakihana, H.

1987-01-01

Band displacement chromatography of magnesium has been carried out successfully for the purpose of magnesium isotope separation by using a strongly acidic cation-exchange resin and the strontium ion as the replacement ion. A small but definite accumulation of the heavier isotopes ( 25 Mg, 26 Mg) has been observed at the front parts of the magnesium chromatograms. The heavier isotopes have been fractionated preferentially into the solution phase. The single-stage separation factors have been calculated for the 25 Mg/ 24 Mg and 26 Mg/ 24 isotopic pairs at 25 0 C. The reduced partition function ratios of magnesium species involved in the present study have been estimated

Identification of fentanyl metabolites in rat urine by gas chromatography-mass spectrometry with stable-isotope tracers

Energy Technology Data Exchange (ETDEWEB)

Goromaru, T.; Matsuura, H.; Furuta, T.; Baba, S.; Yoshimura, N.; Miyawaki, T.; Sameshima, T.

The metabolites of fentanyl (l), which has been widely used as a neuroleptic analgesic agent, were identified in urine of rats by gas chromatography-mass spectrometry combined with a stable-isotope tracer technique. After the oral administration of an equimolar mixture of l and deuterium-labeled l (l/l-d5), the urinary metabolites were extracted with chloroform at pH 9.0. Extracts were derivatized and analyzed by GC/MS. Metabolites were identified by the presence of doublet ion peaks separated by 5 amu, and chemical structures were established from analyses of fragmentation pathways. The metabolites were identified as 4-N-(N-propionylanilino)-piperidine, 4-N-(N-hydroxypropionylanilino)piperidine, 4-N-(N-propionylanilino) hydroxypiperidine, 1-(2-phenethyl)-4-N-(N-hydroxypropionylanilino)piperidine and 1-(2-phenethyl)-4-N-(N-propionylanilino)hydroxypiperidine. These metabolites, together with unchanged l, were also detected in urine of rats receiving l/l-d5 intravenously, by selected-ion monitoring of the specific cluster ions.

Potential application of gas chromatography to the analysis of hydrogen isotopes

International Nuclear Information System (INIS)

Warner, D.K.; Sprague, R.E.; Bohl, D.R.

1976-01-01

Gas chromatography is used at Mound Laboratory for the analysis of hydrogen isotopic impurities in gas mixtures. This instrumentation was used to study the applicability of the gas chromatography technique to the determination of the major components of hydrogen isotopic gas mixtures. The results of this study, including chromatograms and precision data, are presented

Quantification of Fatty Acid Oxidation Products Using On-line High Performance Liquid Chromatography Tandem Mass Spectrometry

Science.gov (United States)

Levison, Bruce S.; Zhang, Renliang; Wang, Zeneng; Fu, Xiaoming; DiDonato, Joseph A.; Hazen, Stanley L.

2013-01-01

Oxidized fatty acids formed via lipid peroxidation are implicated in pathological processes such as inflammation and atherosclerosis. A number of methods may be used to detect specific oxidized fatty acids containing a single or multiple combinations of epoxide, hydroxyl, ketone and hydroperoxide moieties on varying carbon chain lengths from C8 up to C30. Some of these methods are nonspecific and their use in biological systems is fraught with difficulty. Measures of specific-oxidized fatty acid derivatives help in identifying oxidation pathways in pathological processes. We used liquid chromatography coupled with electrospray ionization tandem mass spectrometry (LC-MS/MS) as efficient, selective and sensitive methods for identifying and analyzing multiple specific fatty acid peroxidation products in human plasma and other biological matrices. We then distilled the essential components of a number of these analyses to provide an efficient protocol by which fatty acid oxidation products and their parent compounds can be determined. In this protocol, addition of synthetic internal standard to the sample, followed by base hydrolysis at elevated temperature, and liquid-liquid phase sample extraction with lighter than water solvents facilitates isolation of the oxidized fatty acid species. These species can be identified and accurately quantified using stable isotope dilution and multiple reaction monitoring. Use of a coupled multiplexed gradient HPLC system on the front end enables high-throughput chromatography and more efficient use of mass spectrometer time. PMID:23499838

Doping control analysis of 46 polar drugs in horse plasma and urine using a 'dilute-and-shoot' ultra high performance liquid chromatography-high resolution mass spectrometry approach.

Science.gov (United States)

Kwok, Wai Him; Choi, Timmy L S; Kwok, Karen Y; Chan, George H M; Wong, Jenny K Y; Wan, Terence S M

2016-06-17

The high sensitivity of ultra high performance liquid chromatography coupled with high resolution mass spectrometry (UHPLC-HRMS) allows the identification of many prohibited substances without pre-concentration, leading to the development of simple and fast 'dilute-and-shoot' methods for doping control for human and equine sports. While the detection of polar drugs in plasma and urine is difficult using liquid-liquid or solid-phase extraction as these substances are poorly extracted, the 'dilute-and-shoot' approach is plausible. This paper describes a 'dilute-and-shoot' UHPLC-HRMS screening method to detect 46 polar drugs in equine urine and plasma, including some angiotensin-converting enzyme (ACE) inhibitors, sympathomimetics, anti-epileptics, hemostatics, the new doping agent 5-aminoimidazole-4-carboxamide-1-β-d-ribofuranoside (AICAR), as well as two threshold substances, namely dimethyl sulfoxide and theobromine. For plasma, the sample (200μL) was protein precipitated using trichloroacetic acid, and the resulting supernatant was diluted using Buffer A with an overall dilution factor of 3. For urine, the sample (20μL) was simply diluted 50-fold with Buffer A. The diluted plasma or urine sample was then analysed using a UHPLC-HRMS system in full-scan ESI mode. The assay was validated for qualitative identification purpose. This straightforward and reliable approach carried out in combination with other screening procedures has increased the efficiency of doping control analysis in the laboratory. Moreover, since the UHPLC-HRMS data were acquired in full-scan mode, the method could theoretically accommodate an unlimited number of existing and new doping agents, and would allow a retrospectively search for drugs that have not been targeted at the time of analysis. Copyright © 2016 Elsevier B.V. All rights reserved.

Determination of agmatine using isotope dilution UPLC-tandem mass spectrometry: application to the characterization of the arginine decarboxylase pathway in Pseudomonas aeruginosa

Science.gov (United States)

McCurtain, Jennifer L.; Gilbertsen, Adam J.; Kalstabakken, Kyle A.; Williams, Bryan J.

2018-01-01

A method has been developed for the direct determination of agmatine in bacterial culture supernatants using isotope dilution ultra performance liquid chromatography (UPLC)-tandem mass spectrometry (UPLC-MS/MS). Agmatine determination in bacterial supernatants is comprised of spiking culture or isolate supernatants with a fixed concentration of uniformly labeled 13C5,15N4-agmatine (synthesized by decarboxylation of uniformly labeled 13C6,15N4-arginine using arginine decarboxylase from Pseudomonas aeruginosa) as an internal standard, followed by derivatization with 4-fluoro-7-nitro-2,l,3-benzoxadiazole (NBDF) to improve the reversed-phase chromatographic retention characteristics of agmatine, as well as the selectivity and sensitivity of UPLC-MS/MS detection of this amine in complex biologically derived mixtures. Intrasample precisions for measurement of agmatine in culture supernatants average 4.1 % (relative standard deviation). Calibration curves are linear over the range 5 nM to 10 μM, and the detection limit is estimated at 1.5 nM. To demonstrate the utility of the method, agmatine levels in supernatants of overnight cultures of wild-type (UCBPP-PA14), as well as arginine decarboxylase and agmatine deiminase mutant strains of P. aeruginosa strain UCBPP-PA14 were measured. This method verified that the mutant strains are lacking the specific metabolic capabilities to produce and metabolize agmatine. In addition, measurement of agmatine in supernatants of a panel of clinical isolates from patients with cystic fibrosis revealed that three of the P. aeruginosa isolates hyper-secreted agmatine into the supernatant, hypothesized to be a result of a mutation in the aguA gene. Because agmatine has potential inflammatory activities in the lung, this phenotype may be a virulence factor for P. aeruginosa in the lung environment of cystic fibrosis patients. PMID:25957842

Determination of agmatine using isotope dilution UPLC-tandem mass spectrometry: application to the characterization of the arginine decarboxylase pathway in Pseudomonas aeruginosa.

Science.gov (United States)

Dalluge, Joseph J; McCurtain, Jennifer L; Gilbertsen, Adam J; Kalstabakken, Kyle A; Williams, Bryan J

2015-07-01

A method has been developed for the direct determination of agmatine in bacterial culture supernatants using isotope dilution ultra performance liquid chromatography (UPLC)-tandem mass spectrometry (UPLC-MS/MS). Agmatine determination in bacterial supernatants is comprised of spiking culture or isolate supernatants with a fixed concentration of uniformly labeled (13)C5,(15)N4-agmatine (synthesized by decarboxylation of uniformly labeled (13)C6,(15)N4-arginine using arginine decarboxylase from Pseudomonas aeruginosa) as an internal standard, followed by derivatization with 4-fluoro-7-nitro-2,1,3-benzoxadiazole (NBDF) to improve the reversed-phase chromatographic retention characteristics of agmatine, as well as the selectivity and sensitivity of UPLC-MS/MS detection of this amine in complex biologically derived mixtures. Intrasample precisions for measurement of agmatine in culture supernatants average 4.1% (relative standard deviation). Calibration curves are linear over the range 5 nM to 10 μM, and the detection limit is estimated at 1.5 nM. To demonstrate the utility of the method, agmatine levels in supernatants of overnight cultures of wild-type (UCBPP-PA14), as well as arginine decarboxylase and agmatine deiminase mutant strains of P. aeruginosa strain UCBPP-PA14 were measured. This method verified that the mutant strains are lacking the specific metabolic capabilities to produce and metabolize agmatine. In addition, measurement of agmatine in supernatants of a panel of clinical isolates from patients with cystic fibrosis revealed that three of the P. aeruginosa isolates hyper-secreted agmatine into the supernatant, hypothesized to be a result of a mutation in the aguA gene. Because agmatine has potential inflammatory activities in the lung, this phenotype may be a virulence factor for P. aeruginosa in the lung environment of cystic fibrosis patients.

Evaluation of matrix effect in isotope dilution mass spectrometry based on quantitative analysis of chloramphenicol residues in milk powder

International Nuclear Information System (INIS)

Li, Xiu Qin; Yang, Zong; Zhang, Qing He; Li, Hong Mei

2014-01-01

Graphical abstract: -- Highlights: •We develop a strategy to evaluate matrix effect and its impact on the IDMS results. •Matrix effect and IDMS correction factor from different conditions are evaluated. •Ion suppression effect is observed in LLE and HLB pre-treated sample solutions. •Ion enhancement effect is found in MCX pre-treated sample solution. •IDMS correction factor in HLB and MCX solutions in three instruments is close to 1 -- Abstract: In the present study, we developed a comprehensive strategy to evaluate matrix effect (ME) and its impact on the results of isotope dilution mass spectrometry (IDMS) in analysis of chloramphenicol (CAP) residues in milk powder. Stable isotope-labeled internal standards do not always compensate ME, which brings the variation of the ratio (the peak area of analyte/the peak area of isotope). In our investigation, impact factors of this variation were studied in the extraction solution of milk powder using three mass spectrometers coupled with different ion source designs, and deuterium-labeled chloramphenicol (D5-CAP) was used as the internal standard. ME from mobile phases, sample solvents, pre-treatment methods, sample origins and instruments was evaluated, and its impact on the results of IDMS was assessed using the IDMS correction factor (θ). Our data showed that the impact of ME of mobile phase on the correction factor was significantly greater than that of sample solvent. Significant ion suppression and enhancement effects were observed in different pre-treated sample solutions. The IDMS correction factor in liquid–liquid extraction (LLE) and molecular imprinted polymer (MIP) extract with different instruments was greater or less 1.0, and the IDMS correction factor in hydrophilic lipophilic balance (HLB) and mix-mode cation exchange (MCX) extract with different instruments was all close to 1.0. To the instrument coupled with different ion source design, the impact of ME on IDMS quantitative results was

Application of Isotope Dilution Mass Spectrometry for Reference Measurements of Cadmium. Copper, Mercury, Lead, Zinc and Methyl Mercury in Marine Sediment Sample

Directory of Open Access Journals (Sweden)

Vasileva E.

2013-04-01

Full Text Available Marine sediment was selected as a test sample for the laboratory inter-comparison studies organized by the Environment Laboratoryes of the International Atomic Energy. The analytical procedure to establish the reference values for the Cd, Cu, Hg, Methyl Hg, Pb and Zn amount contents was based on Isotope Dilution Inductively Coupled Plasma-Mass Spectrometry (ID ICP-MS applied as a primary method of measurement..The Hg and Methyl Hg determination will be detailed more specifically because of the problems encountered with this element, including sample homogeneity issues, memory effects and possible matrix effects during the ICP- MS measurement stage. Reference values, traceable to the SI, with total uncertainties of less than 2% relative expanded uncertainty (k=2 were obtained for Cd, Cu, Zn and Pb and around 5% for Hg and CH3Hg.

Validation of multi-element isotope dilution ICPMS for the analysis of basalts

Energy Technology Data Exchange (ETDEWEB)

Willbold, M.; Jochum, K.P.; Raczek, I.; Amini, M.A.; Stoll, B.; Hofmann, A.W. [Max-Planck-Institut fuer Chemie, Mainz (Germany)

2003-09-01

In this study we have validated a newly developed multi-element isotope dilution (ID) ICPMS method for the simultaneous analysis of up to 12 trace elements in geological samples. By evaluating the analytical uncertainty of individual components using certified reference materials we have quantified the overall analytical uncertainty of the multi-element ID ICPMS method at 1-2%. Individual components include sampling/weighing, purity of reagents, purity of spike solutions, calibration of spikes, determination of isotopic ratios, instrumental sources of error, correction of mass discrimination effect, values of constants, and operator bias. We have used the ID-determined trace elements for internal standardization to improve indirectly the analysis of 14 other (mainly mono-isotopic trace elements) by external calibration. The overall analytical uncertainty for those data is about 2-3%. In addition, we have analyzed USGS and MPI-DING geological reference materials (BHVO-1, BHVO-2, KL2-G, ML3B-G) to quantify the overall bias of the measurement procedure. Trace element analysis of geological reference materials yielded results that agree mostly within about 2-3% relative to the reference values. Since these results match the conclusions obtained by the investigation of the overall analytical uncertainty, we take this as a measure for the validity of multi-element ID ICPMS. (orig.)

Assay of cortisol with a radioimmunoassay method calibrated by isotope dilution-mass spectrometry. A Nordic collaborative study

International Nuclear Information System (INIS)

Lantto, O.; Lindback, B.; Aakvaag, A.; Bjoerkhem, I.; Damkjaer-Nielsen, M.; Pomoell, U.M.; Helsinki University Hospital

1983-01-01

A reference method for serum cortisol, based on isotope dilution-mass spectrometry (ID-MS), was compared with a modified commercial RIA method. The modification solely concerned the calibration standards used in the RIA method. These were replaced by a series of human serum samples, in which the concentration of cortisol had been determined by the reference ID-MS method. Samples were selected to cover the whole range of the standard curve. Serum samples from healthy, untreated subjects with cortisol concentrations 270-1134 nmol/l were analysed with the ID-MS calibrated RIA method in four laboratories, one in each of the four Nordic countries. Mean values based on results from all four laboratories were almost identical with the values obtained with the reference method. Serum samples from 11 patients with endocrine disorders with cortisol concentrations 31-916 nmol/l were analysed in three of the four laboratories. In three of the samples significant differences were observed between the values obtained with the ID-MS and the ID-MS calibrated RIA method. The value obtained with the ID-MS calibrated RIA was however always more accurate than the corresponding value obtained with RIA with the use of a commercial calibration standard. (author)

Accurate quantification of polycyclic aromatic hydrocarbons in dust samples using microwave-assisted solvent extraction combined with isotope-dilution mass spectrometry

International Nuclear Information System (INIS)

Itoh, Nobuyasu; Fushimi, Akihiro; Yarita, Takashi; Aoyagi, Yoshie; Numata, Masahiko

2011-01-01

Highlights: → We applied MAE-IDMS for accurate quantification of PAHs in dust samples. → Both partitioning and isotopic equilibria can be achieved using this technique. → MAE-IDMS can provide accurate concentrations even if extraction efficiencies were low. → Characteristics of samples strongly affected for low extraction efficiencies of PAHs. - Abstract: For accurate quantification of polycyclic aromatic hydrocarbons (PAHs) in dust samples, we investigated the use of microwave-assisted solvent extraction (MAE) combined with isotope-dilution mass spectrometry (IDMS) using deuterium-labelled PAHs (D-PAHs). Although MAE with a methanol/toluene mixture (1:3 by volume) at 160 deg. C for 40 min was best for extracting PAHs from tunnel dust among examined, the recovery yields of D-PAHs decreased with increasing molecular weight (<40% for MW ≥ 264; that of deuterium-labelled indeno[123-cd]pyrene (D-IcdP) was only 7.1%). Although the residues were extracted a second time, the observed concentrations did not change dramatically (<5%), and the recovery yields of heavier D-PAHs (i.e., MW ≥ 264) were approximately half of those of the first extract, including D-IcdP (3.4%). These results suggest that both partitioning and isotopic equilibria of PAHs and D-PAHs between sample and solvent were achieved for extractable heavier PAHs under the condition. Thus, the observed concentrations of PAHs obtained by MAE-IDMS were reasonable, even though recovery yields of D-PAHs were <50%. From the results of carbon analyses and extractable contents, lower recovery yields of D-PAHs from the tunnel dust were due to a large content of char with low extractable contents.

High-precision quadruple isotope dilution method for simultaneous determination of nitrite and nitrate in seawater by GCMS after derivatization with triethyloxonium tetrafluoroborate

Energy Technology Data Exchange (ETDEWEB)

Pagliano, Enea, E-mail: enea.pagliano@nrc-cnrc.gc.ca; Meija, Juris; Mester, Zoltán

2014-05-01

Highlights: • High-precision determination of nitrite and nitrate in seawater. • Use of quadruple isotope dilution. • Aqueous Et₃O⁺BF₄]⁻ derivatization chemistry for GCMS analysis of nitrite and nitrate. Abstract: Quadruple isotope dilution mass spectrometry (ID⁴MS) has been applied for simultaneous determination of nitrite and nitrate in seawater. ID⁴MS allows high-precision measurements and entails the use of isotopic internal standards (¹⁸O-nitrite and ¹⁵N-nitrate). We include a tutorial on ID⁴MS outlining optimal experimental design which generates results with low uncertainties and obviates the need for direct (separate) evaluation of the procedural blank. Nitrite and nitrate detection was achieved using a headspace GCMS procedure based on single-step aqueous derivatization with triethyloxonium tetrafluoroborate at room temperature. In this paper the sample preparation was revised and fundamental aspects of this chemistry are presented. The proposed method has detection limits in the low parts-per-billion for both analytes, is reliable, precise, and has been validated using a seawater certified reference material (MOOS-2). Simplicity of the experimental design, low detection limits, and the use of quadruple isotope dilution makes the present method superior to the state-of-the-art for determination of nitrite and nitrate, and an ideal candidate for reference measurements of these analytes in seawater.

Internal correction of spectral interferences and mass bias for selenium metabolism studies using enriched stable isotopes in combination with multiple linear regression.

Science.gov (United States)

Lunøe, Kristoffer; Martínez-Sierra, Justo Giner; Gammelgaard, Bente; Alonso, J Ignacio García

2012-03-01

The analytical methodology for the in vivo study of selenium metabolism using two enriched selenium isotopes has been modified, allowing for the internal correction of spectral interferences and mass bias both for total selenium and speciation analysis. The method is based on the combination of an already described dual-isotope procedure with a new data treatment strategy based on multiple linear regression. A metabolic enriched isotope ((77)Se) is given orally to the test subject and a second isotope ((74)Se) is employed for quantification. In our approach, all possible polyatomic interferences occurring in the measurement of the isotope composition of selenium by collision cell quadrupole ICP-MS are taken into account and their relative contribution calculated by multiple linear regression after minimisation of the residuals. As a result, all spectral interferences and mass bias are corrected internally allowing the fast and independent quantification of natural abundance selenium ((nat)Se) and enriched (77)Se. In this sense, the calculation of the tracer/tracee ratio in each sample is straightforward. The method has been applied to study the time-related tissue incorporation of (77)Se in male Wistar rats while maintaining the (nat)Se steady-state conditions. Additionally, metabolically relevant information such as selenoprotein synthesis and selenium elimination in urine could be studied using the proposed methodology. In this case, serum proteins were separated by affinity chromatography while reverse phase was employed for urine metabolites. In both cases, (74)Se was used as a post-column isotope dilution spike. The application of multiple linear regression to the whole chromatogram allowed us to calculate the contribution of bromine hydride, selenium hydride, argon polyatomics and mass bias on the observed selenium isotope patterns. By minimising the square sum of residuals for the whole chromatogram, internal correction of spectral interferences and mass

Isotope dilution alpha spectrometry for the determination of plutonium concentration in irradiated fuel dissolver solution : IDAS and R-IDAS

International Nuclear Information System (INIS)

Ramaniah, M.V.; Jain, H.C.; Aggarwal, S.K.; Chitambar, S.A.; Kavimandan, V.D.; Almaula, A.I.; Shah, P.M.; Parab, A.R.; Sant, V.L.

1980-01-01

The report presents a new technique, Isotope Dilution Alpha Spectrometry (IDAS) and Reverse Isotope Dilution Alpha Spectrometry (R-IDAS) for determining the concentration of plutonium in the irradiated fuel dissolver solution. The method exploits sup(238)Pu in IDAS and sup(239)Pu in R-IDAS as a spike and provides an alternative method to Isotope Dilution Mass Spectrometry (IDMS) which requires enriched sup(242)Pu as a spike. Depending upon the burn-up of the fuel, sup(238)Pu or sup(239)Pu is used as a spike to change the sup(238)Pu/(sup(239)Pu+sup(240)Pu)α activity ratio in the sample by a factor of 10. This change is determined by α-spectrometry on electrodeposited sources using a solid state silicon surface barrier detector coupled to a multichannel analyser. The validity of a simple method based on the geometric progression (G.P.) decrease for the far tail of the spectrum to correct for the tail contribution of sup(238)Pu peak (5.50 MeV) to the low energy sup(239)Pu + sup(240)Pu peak (5.17 MeV) is established. Results for the plutonium concentration on different irradiated fuel dissolver solutions with burn-uo ranging from J,000 to 100,000 MWD/TU are presented and compared with those obtained by IDMS. The values obtained by IDAS or R-IDAS and IDMS agree within 0.5%. (auth.)

High-precision measurement of phenylalanine δ15N values for environmental samples: a new approach coupling high-pressure liquid chromatography purification and elemental analyzer isotope ratio mass spectrometry.

Science.gov (United States)

Broek, Taylor A B; Walker, Brett D; Andreasen, Dyke H; McCarthy, Matthew D

2013-11-15

Compound-specific isotope analysis of individual amino acids (CSI-AA) is a powerful new tool for tracing nitrogen (N) source and transformation in biogeochemical cycles. Specifically, the δ(15)N value of phenylalanine (δ(15)N(Phe)) represents an increasingly used proxy for source δ(15)N signatures, with particular promise for paleoceanographic applications. However, current derivatization/gas chromatography methods require expensive and relatively uncommon instrumentation, and have relatively low precision, making many potential applications impractical. A new offline approach has been developed for high-precision δ(15)N measurements of amino acids (δ(15)N(AA)), optimized for δ(15)N(Phe) values. Amino acids (AAs) are first purified via high-pressure liquid chromatography (HPLC), using a mixed-phase column and automated fraction collection. The δ(15)N values are determined via offline elemental analyzer-isotope ratio mass spectrometry (EA-IRMS). The combined HPLC/EA-IRMS method separated most protein AAs with sufficient resolution to obtain accurate δ(15)N values, despite significant intra-peak isotopic fractionation. For δ(15)N(Phe) values, the precision was ±0.16‰ for standards, 4× better than gas chromatography/combustion/isotope ratio mass spectrometry (GC/C/IRMS; ±0.64‰). We also compared a δ(15)N(Phe) paleo-record from a deep-sea bamboo coral from Monterey Bay, CA, USA, using our method versus GC/C/IRMS. The two methods produced equivalent δ(15)N(Phe) values within error; however, the δ(15)N(Phe) values from HPLC/EA-IRMS had approximately twice the precision of GC/C/IRMS (average stdev of 0.27‰ ± 0.14‰ vs 0.60‰ ± 0.20‰, respectively). These results demonstrate that offline HPLC represents a viable alternative to traditional GC/C/IMRS for δ(15)N(AA) measurement. HPLC/EA-IRMS is more precise and widely available, and therefore useful in applications requiring increased precision for data interpretation (e.g. δ(15)N paleoproxies

High accuracy determination of trace elements in NIST standard reference materials by isotope dilution ICP-MS

International Nuclear Information System (INIS)

Paulsen, P.J.; Beary, E.S.

1996-01-01

At NIST (National Institute of Standards and Technology), ICP-MS ID (inductively coupled mass spectrometry isotope dilution) has been used to certify a wide range of elements in a variety of materials with high accuracy. Both the chemical preparation and instrumental procedures are simpler than with other ID mass spectrometric techniques. The ICP-MS has picogram/ml detection limits for most elements using fixed operating parameters. Chemical separations are required only to remove an interference (from molecular ions as well as isobaric atoms), or to pre-concentrate the analyte. For example, chemical separations were required for the analysis of SRM 2711, Montana II Soil, but not for boron in peach leaves, SRM 1547.(3 refs., 3 tabs., 2 figs

Stable isotope dilution assay (SIDA) and HS-SPME-GCMS quantification of key aroma volatiles for fruit and sap of Australian mango cultivars.

Science.gov (United States)

San, Anh T; Joyce, Daryl C; Hofman, Peter J; Macnish, Andrew J; Webb, Richard I; Matovic, Nicolas J; Williams, Craig M; De Voss, James J; Wong, Siew H; Smyth, Heather E

2017-04-15

Reported herein is a high throughput method to quantify in a single analysis the key volatiles that contribute to the aroma of commercially significant mango cultivars grown in Australia. The method constitutes stable isotope dilution analysis (SIDA) in conjunction with headspace (HS) solid-phase microextraction (SPME) coupled with gas-chromatography mass spectrometry (GCMS). Deuterium labelled analogues of the target analytes were either purchased commercially or synthesised for use as internal standards. Seven volatiles, hexanal, 3-carene, α-terpinene, p-cymene, limonene, α-terpinolene and ethyl octanoate, were targeted. The resulting calibration functions had determination coefficients (R 2 ) ranging from 0.93775 to 0.99741. High recovery efficiencies for spiked mango samples were also achieved. The method was applied to identify the key aroma volatile compounds produced by 'Kensington Pride' and 'B74' mango fruit and by 'Honey Gold' mango sap. This method represents a marked improvement over current methods for detecting and measuring concentrations of mango fruit and sap volatiles. Copyright © 2016 Elsevier Ltd. All rights reserved.

Calcium isotope fractionation in ion-exchange chromatography

International Nuclear Information System (INIS)

Russell, W.A.; Papanastassiou, D.A.

1978-01-01

Significant fractionation of the isotopes of calcium has been observed during elution through short ion-exchange columns packed with Dowex 50W-X8 resin. A double isotopic tracer was used to provide correction for instrumental fractionation effects. The absolute 40 Ca/ 44 Ca ratio is determined by this method to 0.05% and provides a measure of the fractionation of all Ca isotopes. It is found that the lighter isotopes are preferentially retained by the resin, with variations in 40 Ca/ 44 Ca between the first and last fractions of up to 1.1%. An estimate of the separation factor between batch solute and resin gives epsilon = 2.1 x 10 -4 . Details of the chemical or physical mechanisms causing isotope fractionation of Li, Na, Ca, and other elements during ion-exchange chromatography are not yet clear

Measurement of rimantadine in plasma by capillary gas chromatography/mass spectrometry with a deuterium-labeled internal standard

International Nuclear Information System (INIS)

Herold, D.A.; Anonick, P.K.; Kinter, M.; Hayden, F.G.

1988-01-01

Rimantadine is a synthetic antiviral agent used in prophylaxis and in treating the early stages of uncomplicated influenza A illness. We describe a stable isotope-dilution assay involving capillary gas chromatography/mass spectrometry. We used 200 ng of d3-rimantadine, added to 1 mL of plasma, as the internal standard. The rimantadine was extracted from the plasma with a Bond-Elut CN column, the column was washed with water, and the rimantadine was eluted with methanol, dried, and treated to form the t-butyldimethylsilyl derivative. The mass spectrometer was operated in the selected ion monitoring mode. Ions at m/z 236 and m/z 239 were monitored, corresponding to the loss of C4H9 from the rimantadine derivative and d3-rimantadine, respectively. Within-run precision (CVs) ranged from 8.9% at 29 micrograms/L to 3.2% at 1666 micrograms/L. Corresponding data for between-run precision were 5.4% and 1.7%. Treated volunteers (n = 86) provided plasma samples with a concentration range of 153 to 1127 micrograms/L. This simplified method allows rapid, precise assay of rimantadine in plasma

Quantification of transformation rates of soil amino sugars and amino acids by a novel isotope pool dilution approach via liquid chromatography/high resolution mass spectrometry (LC/HRMS)

Science.gov (United States)

Hu, Yuntao; Zheng, Qing; Noll, Lisa; Zhang, Shasha; Wanek, Wolfgang

2017-04-01

Organic nitrogen transformation processes are the key driver of soil nitrogen availability, strongly affecting the nitrogen turnover and carbon cycling of terrestrial ecosystems. Low molecular weight organic nitrogen compounds (e.g. amino acids and amino sugars) that can be directly utilized by plants or microorganisms are released by the extracellular cleavage of high molecular weight organic nitrogen compounds (e.g. proteins, peptidoglycan, and chitin) by hydrolytic enzymes. This decomposition process is believed to be the rate-limiting step in the soil N cycle. Direct measurements of the in situ transformation rates of these small N compounds is highly challenging but can be realized by applying the isotope pool dilution (IPD) technique, in which the target compound pool is labeled with isotopic tracers and subsequently the dilution of the tracers is measured. We have recently pioneered the development of IPD assays to investigate the in situ flux of proteinaceous amino acids and glucose due to decomposition of organic matter and microbial utilization, but the roles of fluxes of amino sugars and amino acid enantiomers in soil nitrogen transformation processes are still unknown due to the lack of feasible extraction, purification, separation and detection methods. Here we developed a 15N IPD assay by utilizing a novel LC/HRMS (Orbitrap) platform, with the aim to measure transformation rates of amino sugars and amino acid enantiomers. After the tracer experiments soil extracts were purified by solid phase extraction prior to the analysis by MS. The utilization of Orbitrap-HRMS allowed us to resolve the mass signals of unlabeled analytes, and their 15N labeled (tracers) and 13C labeled (internal standards) analogues. The commercially unavailable 15N and 13C labeled amino sugars and amino acid enantiomers were produced from bacterial cell walls after batch culture in labeled growth media. This workflow was validated with soils from two sampling sites, allowing us to

Hyphenation of supercritical fluid chromatography with tandem mass spectrometry for fast determination of four aflatoxins in edible oil.

Science.gov (United States)

Lei, Fang; Li, Chenglong; Zhou, Shuang; Wang, Dan; Zhao, Yunfeng; Wu, Yongning

2016-08-01

Aflatoxins (AFTs) are of great concern all over the world. Supercritical fluid chromatography (SFC) has the advantage of fast, high resolution and excellent compatibility with a broad range of organic solvents and samples, thus hyphenating SFC with tandem mass spectrometry (MS/MS) can be used for the easy and fast determination of AFTs in edible oils. Edible oil was spiked with isotope-labeled aflatoxin standards, diluted with hexane and extracted with acetonitrile. The extraction was directly loaded to an SFC apparatus and separated on a UPC(2) 2-EP column with CO2 -methanol gradient elution. A post-column make-up flow was introduced to facilitate mass spectrometry performance, and the mixture was analyzed by MS/MS with an electrospray ionization (ESI) source. The SFC conditions including separation column, modifier and sample solvent were optimized, and the four target aflatoxins were baseline separated. The ESI interface parameters were also investigated, implicating the make-up flow as a critical factor for sensitive determination by SFC-MS/MS. The LOQs for the AFTs were 0.05-0.12 μg L(-1) , while the RSDs were lower than 8.5%. Supercritical fluid chromatography was successfully coupled to tandem mass spectrometry to establish a simple, fast and sensitive method for the analysis of four aflatoxins in edible oil. This shows the combination of SFC-MS/MS has great potential in determination of trace contaminants in food. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Boron isotope fractionation in column chromatography with glucamine type fibers

International Nuclear Information System (INIS)

Sonoda, Akinari; Makita, Yoji; Hirotsu, Takahiro

2008-01-01

Glucamine type polymers have specific affinity toward boric acid and borate ion. Among them, Chelest Fiber GRY-L showed larger fractionation for boron isotopes than other polymers in our previous study. For this study, we used Chelest Fibers with different fiber lengths (1.0 mm, 0.5 mm, and 0.3 mm) as column packing materials to perform chromatographic separation of boron isotopes. The shorter fiber has larger packing density when packed into the column using a dry method. The 0.3-mm-long fiber has a larger backpressure than fibers of other lengths. Boron adsorption capacities were measured using the breakthrough operation. At this time, the 0.5-mm-long fiber showed the highest capacity. When we measured the isotope ratio profile for fibers of different length using column chromatography, 0.5-mm-long fibers displayed the highest boron isotope fractionation. The 0.5-mm-long fiber is promising as a packing material of column chromatography for boron isotope separation. We also changed operation methods. The lower eluent concentration and the slower flow rate are suitable for boron isotope separation. (author)

Single-step transesterification with simultaneous concentration and stable isotope analysis of fatty acid methyl esters by gas chromatography-combustion-isotope ratio mass spectrometry.

Science.gov (United States)

Panetta, Robert J; Jahren, A Hope

2011-05-30

Gas chromatography-combustion-isotope ratio mass spectrometry (GC-C-IRMS) is increasingly applied to food and metabolic studies for stable isotope analysis (δ(13) C), with the quantification of analyte concentration often obtained via a second alternative method. We describe a rapid direct transesterification of triacylglycerides (TAGs) for fatty acid methyl ester (FAME) analysis by GC-C-IRMS demonstrating robust simultaneous quantification of amount of analyte (mean r(2) =0.99, accuracy ±2% for 37 FAMEs) and δ(13) C (±0.13‰) in a single analytical run. The maximum FAME yield and optimal δ(13) C values are obtained by derivatizing with 10% (v/v) acetyl chloride in methanol for 1 h, while lower levels of acetyl chloride and shorter reaction times skewed the δ(13) C values by as much as 0.80‰. A Bland-Altman evaluation of the GC-C-IRMS measurements resulted in excellent agreement for pure oils (±0.08‰) and oils extracted from French fries (±0.49‰), demonstrating reliable simultaneous quantification of FAME concentration and δ(13) C values. Thus, we conclude that for studies requiring both the quantification of analyte and δ(13) C data, such as authentication or metabolic flux studies, GC-C-IRMS can be used as the sole analytical method. Copyright © 2011 John Wiley & Sons, Ltd.

Determination of photooxygenation products of rotenone with isotope dilution method

International Nuclear Information System (INIS)

Chubachi, Mitsuo; Hamada, Masayuki

1975-01-01

When rotenone dissolved in certain solvent was photochemically oxidized, rotenolones, dehydrorotenone and rotenonone were obtained as main products. In order to determine the quantitative yields of these compounds in photooxygenation products, four compounds mentioned above were labeled with carbon-14 and the isotope dilution method by these labeled compounds was applied to the product analysis. (auth.)

Stable Isotope Quantitative N-Glycan Analysis by Liquid Separation Techniques and Mass Spectrometry.

Science.gov (United States)

Mittermayr, Stefan; Albrecht, Simone; Váradi, Csaba; Millán-Martín, Silvia; Bones, Jonathan

2017-01-01

Liquid phase separation analysis and subsequent quantitation remains a challenging task for protein-derived oligosaccharides due to their inherent structural complexity and diversity. Incomplete resolution or co-detection of multiple glycan species complicates peak area-based quantitation and associated statistical analysis when optical detection methods are used. The approach outlined herein describes the utilization of stable isotope variants of commonly used fluorescent tags that allow for mass-based glycan identification and relative quantitation following separation by liquid chromatography (LC) or capillary electrophoresis (CE). Comparability assessment of glycoprotein-derived oligosaccharides is performed by derivatization with commercially available isotope variants of 2-aminobenzoic acid or aniline and analysis by LC- and CE-mass spectrometry. Quantitative information is attained from the extracted ion chromatogram/electropherogram ratios generated from the light and heavy isotope clusters.

Redox substoichiometry in isotope dilution analysis Pt. 4

International Nuclear Information System (INIS)

Kambara, T.; Yoshioka, H.; Ugai, Y.

1980-01-01

The oxidation reaction of antimony(III) with potassium dichromate has been investigated radiometrically. The quantitative oxidation of antimony(III) was found to be not disturbed even in large amounts of tin(IV). On the basis of these results the redox substoichiometric isotope dilution analysis using potassium dichromate as the oxidizing agent was proposed for the determination of antimony in metallic tin. An antimony content of 1.22+-0.05 μg in metallic tin (10 mg) was determined without separation of the matrix element. (author)

Preparation of [13C3]-melamine and [13C3]-cyanuric acid and their application to the analysis of melamine and cyanuric acid in meat and pet food using liquid chromatography-tandem mass spectrometry.

Science.gov (United States)

Varelis, P; Jeskelis, R

2008-10-01

For the determination of melamine and cyanuric acid the labelled internal standards [(13)C(3)]-melamine and [(13)C(3)]-cyanuric acid were synthesized using the common substrate [(13)C(3)]-cyanuric chloride by reaction with ammonia and acidified water, respectively. Standards with excellent isotopic and chemical purities were obtained in acceptable yields. These compounds were used to develop an isotope dilution liquid chromatography/mass spectrometry (LC/MS) method to determine melamine and cyanuric acid in catfish, pork, chicken, and pet food. The method involved extraction into aqueous methanol, liquid-liquid extraction and ion exchange solid phase clean-up, with normal phase high-performance liquid chromatography (HPLC) in the so-called hydrophilic interaction mode. The method had a limit of detection (LOD) of 10 microg kg(-1) for both melamine and cyanuric acid in the four foods with a percentage coefficient of variation (CV) of less than 10%. The recovery of the method at this level was in the range of 87-110% and 96-110% for melamine and cyanuric acid, respectively.

Validity of the tritiated thymidine method for estimating bacterial growth rates: measurement of isotope dilution during DNA synthesis

International Nuclear Information System (INIS)

Pollard, P.C.; Moriarty, D.J.W.

1984-01-01

The rate of tritiated thymidine incorporation into DNA was used to estimate bacterial growth rates in aquatic environments. To be accurate, the calculation of growth rates has to include a factor for the dilution of isotope before incorporation. The validity of an isotope dilution analysis to determine this factor was verified in experiments reported here with cultures of a marine bacterium growing in a chemostat. Growth rates calculated from data on chemostat dilution rates and cell density agreed well with rates calculated by tritiated thymidine incorporation into DNA and isotope dilution analysis. With sufficiently high concentrations of exogenous thymidine, de novo synthesis of deoxythymidine monophosphate was inhibited, thereby preventing the endogenous dilution of isoope. The thymidine technique was also shown to be useful for measuring growth rates of mixed suspensions of bacteria growing anaerobically. Thymidine was incorporated into the DNA of a range of marine pseudomonads that were investigated. Three species did not take up thymidine. The common marine cyanobacterium Synechococcus species did not incorporate thymidine into DNA

Easy Extraction Method To Evaluate δ13C Vanillin by Liquid Chromatography-Isotopic Ratio Mass Spectrometry in Chocolate Bars and Chocolate Snack Foods.

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Bononi, Monica; Quaglia, Giancarlo; Tateo, Fernando

2015-05-20

An easy extraction method that permits the use of a liquid chromatography-isotopic ratio mass spectrometry (LC-IRMS) system to evaluate δ(13)C of vanillin in chocolate products and industrial flavorings is presented. The method applies the determination of stable isotopes of carbon to discriminate between natural vanillin from vanilla beans and vanillin from other sources (mixtures from beans, synthesis, or biotechnology). A series of 13 chocolate bars and chocolate snack foods available on the Italian market and 8 vanilla flavorings derived from industrial quality control processes were analyzed. Only 30% of products considered in this work that declared "vanilla" on the label showed data that permitted the declaration "vanilla" according to European Union (EU) Regulation 1334/2008. All samples not citing "vanilla" or "natural flavoring" on the label gave the correct declaration. The extraction method is presented with data useful for statistical evaluation.

Evaluation of isotopic dilution method for measuring N2 fixation in azolla: comparison with other methods

International Nuclear Information System (INIS)

Sah, R.N.; Goyal, S.S.; Rains, D.W.; Paige, D.F.

1989-01-01

An isotopic dilution method that overcomes the drawbacks of commonly used methods for measuring N 2 fixation by aquatic N‐fixers such as Azolla pinnata‐Anabaena azollae association (Azolla) is presented. The method was compared with 15 N2 gas (while maintaining CO 2 ) and the difference methods of measuring N 2 fixation. The isotopic dilution method was used for two conditions: a. For 15 N‐free growth medium, Azolla was pre‐enriched with 15 N, and N 2 fixation was determined by measuring the dilution of 15 N in the tissue. b. For the growth medium containing N, N2 fixation was determined by providing 15 N enriched ammonium sulfate in the growth medium and measuring 15 N to 14 N ratio in the tissue. An airtight chamber, necessary for 15 N 2 gas and acetylene reduction methods, was not representative of the growing environment of Azolla. Temperature in the airtight chamber was far from uniform and CO 2 was rapidly depleted. The isotopic dilution method is simpler, relatively inexpensive, subject to fewer errors and applicable to more diverse conditions, and yet was as accurate as 15 N2‐gas method. (author)

Determination of selected endogenous anabolic androgenic steroids and ratios in urine by ultra high performance liquid chromatography tandem mass spectrometry and isotope pattern deconvolution.

Science.gov (United States)

Pitarch-Motellón, J; Sancho, J V; Ibáñez, M; Pozo, O; Roig-Navarro, A F

2017-09-15

An isotope dilution mass spectrometry (IDMS) method for the determination of selected endogenous anabolic androgenic steroids (EAAS) in urine by UHPLC-MS/MS has been developed using the isotope pattern deconvolution (IPD) mathematical tool. The method has been successfully validated for testosterone, epitestosterone, androsterone and etiocholanolone, employing their respective deuterated analogs using two certified reference materials (CRM). Accuracy was evaluated as recovery of the certified values and ranged from 75% to 108%. Precision was assessed in intraday (n=5) and interday (n=4) experiments, with RSDs below 5% and 10% respectively. The method was also found suitable for real urine samples, with limits of detection (LOD) and quantification (LOQ) below the normal urinary levels. The developed method meets the requirements established by the World Anti-Doping Agency for the selected steroids for Athlete Biological Passport (ABP) measurements, except in the case of androsterone, which is currently under study. Copyright © 2017. Published by Elsevier B.V.

Certification of the Cu and Cd amount contents in artificial food digest using isotope dilution inductively coupled plasma mass spectrometry for Pilot Study 13 of the Comite Consultatif pour la Quantite de Matiere

International Nuclear Information System (INIS)

Vassileva, E.; Quetel, C.R.; Petrov, I.

2003-01-01

The Comite Consultatif pour la Quantite de Matiere (CCQM) launched the Pilot Study 13, an interlaboratory comparison between the metrological organizations worldwide on the determination of Ca, Cu and Cd in artificial food digests. These samples (available in 7% HNO 3 and with a salinity evaluated around 370 mg kg -1 , including approx. 30 mg Na kg -1 ) were prepared by gravimetrical mixing, and thus reference values traceable to the Kg for the three elements were available eventually. This paper describes the contribution of IRMM for the certification of the Cu and the Cd amount contents. The analytical protocol developed was based on isotope dilution associated to inductively coupled plasma mass spectrometry (ID-ICP-MS). The Cu measurements required 125-fold dilution of the initial sample solution. An interference of 23 Na 40 Ar + on 63 Cu + was identified but, since the ratio between both species was over 1000, it was successfully overcome by the calculation of a correction factor for its effect on the Cu amount content directly. Dilution of the sample was not possible for Cd only present at the low ng g -1 level. Up to 1% difference was observed on Cd isotope ratio results between measurements performed directly or after matrix separation. This is rarely shown. As similar results could be obtained either way after the necessary corrections, the direct measurements approach associated to a correction for mass discrimination effects using the CCQM-P13 sample itself (and the IUPAC table values as reference for the natural Cd isotopic composition) was preferred as it was the easiest. SI traceable values were obtained for Cu and Cd with less than 1 and 1.5% combined uncertainty, respectively (6 995±55 (k=2) nmol kg -1 and 45.53±0.64 (k=2) nmol kg -1 ). The excellent agreement between these results and the reference values (less than 0.6 and 0.08% difference) further validated the analytical protocols developed

Pentafluorobenzyl bromide-A versatile derivatization agent in chromatography and mass spectrometry: I. Analysis of inorganic anions and organophosphates.

Science.gov (United States)

Tsikas, Dimitrios

2017-02-01

Pentafluorobenzyl bromide (PFB-Br) is a versatile derivatization agent. It is widely used in chromatography and mass spectrometry since several decades. The bromide atom is largely the single leaving group of PFB-Br. It is substituted by wide a spectrum of nucleophiles in aqueous and non-aqueous systems to form electrically neutral, in most organic solvents soluble, generally thermally stable, volatile, strongly electron-capturing and ultraviolet light-absorbing derivatives. Because of these greatly favoured physicochemical properties, PFB-Br emerged an ideal derivatization agent for highly sensitive analysis of endogenous and exogenous substances including various inorganic and organic anions by electron capture detection or after electron-capture negative-ion chemical ionization in GC-MS. The present article attempts an appraisal of the utility of PFB-Br in analytical chemistry. It reviews and discusses papers dealing with the use of PFB-Br as the derivatization reagent in the qualitative and quantitative analysis of endogenous and exogenous inorganic anions in various biological samples, notably plasma, urine and saliva. These analytes include nitrite, nitrate, cyanide and dialkyl organophosphates. Special emphasis is given to mass spectrometry-based approaches and stable-isotope dilution techniques. Copyright © 2016 Elsevier B.V. All rights reserved.

An improved high-performance liquid chromatography-tandem mass spectrometric method to measure atrazine and its metabolites in human urine.

Science.gov (United States)

Panuwet, Parinya; Restrepo, Paula A; Magsumbol, Melina; Jung, Kyung Y; Montesano, M Angela; Needham, Larry L; Barr, Dana Boyd

2010-04-15

We report an improved solid-phase extraction-high-performance liquid chromatography-tandem mass spectrometry method with isotope dilution quantification to measure seven atrazine metabolites in urine. The metabolites measured were hydroxyatrazine (HA), diaminochloroatrazine (DACT), desisopropylatrazine (DIA), desethylatrazine (DEA), desethylatrazine mercapturate (DEAM), atrazine mercapturate (ATZM), and atrazine (ATZ). Using offline mixed-mode reversed-phase/cation-exchange solid-phase extraction dramatically increased recovery and sensitivity by reducing the influence of matrix components during separation and analysis. DACT extraction recovery improved to greater than 80% while the other analytes had similar extraction efficiencies as previously observed. Limits of detection were lower than our previous method (0.05-0.19 ng/mL) with relative standard deviations less than 10%. The total runtime was shorter (18 min) than the previous on-line method, thus it is suitable for large-scale sample analyses. We increased the throughput of our method twofold by using the newer extraction technique. Published by Elsevier B.V.

Protein Stable Isotope Fingerprinting (P-SIF): Multidimensional Protein Chromatography Coupled to Stable Isotope-Ratio Mass Spectrometry

Science.gov (United States)

Pearson, A.; Bovee, R. J.; Mohr, W.; Tang, T.

2012-12-01

As metagenomics increases our insight into microbial community diversity and metabolic potential, new approaches are required to determine the biogeochemical expression of this potential within ecosystems. Because stable isotopic analysis of the major bioactive elements (C, N) has been used historically to map flows of substrates and energy among macroscopic food webs, similar principles may apply to microbes. To address this challenge, we have developed a new analytical approach called Protein Stable Isotope Fingerprinting (P-SIF). P-SIF generates natural stable isotopic fingerprints of microbial individual or community proteomes. The main advantage of P-SIF is the potential to bridge the gap between diversity and function, thereby providing a window into the "black box" of environmental microbiology and helping to decipher the roles of uncultivated species. Our method implements a three-way, orthogonal scheme to separate mixtures of whole proteins into subfractions dominated by single or closely-related proteins. Protein extracts first are isoelectrically focused in a gel-free technique that yields 12 fractions separated over a gradient of pH 3-10. Each fraction then is separated by size-exclusion chromatography into 20 pools, ranging from >100kD to ~10kD. Finally, each of these pools is subjected to HPLC and collected in 40 time-slices based on protein hydrophobicity. Theoretical calculation reveals that the true chromatographic resolution of the total scheme is 5000, somewhat less than the 9600 resulting fractions. High-yielding fractions are subjected to δ13C analysis by spooling-wire microcombustion irMS (SWiM-irMS) optimized for samples containing 1-5 nmol carbon. Here we will present the method, results for a variety of pure cultures, and preliminary data for a sample of mixed environmental proteins. The data show the promise of this method for unraveling the metabolic complexity hidden within microbial communities.

Potential of ion chromatography coupled to isotope ratio mass spectrometry via a liquid interface for beverages authentication.

Science.gov (United States)

Guyon, Francois; Gaillard, Laetitia; Brault, Audrey; Gaultier, Nicolas; Salagoïty, Marie-Hélène; Médina, Bernard

2013-12-27

New tools for the determination of characteristic parameters for food authentication are requested to prevent food adulteration from which health concerns, unfair competition could follow. A new coupling in the area of compound-specific carbon 13 isotope ratio (δ(13)C) analysis was developed to simultaneously quantify δ(13)C values of sugars and organic acids. The coupling of ion chromatography (IC) together with isotope ratio mass spectrometry (IRMS) can be achieved using a liquid interface allowing a chemical oxidation (co) of organic matter. Synthetic solutions containing 1 polyol (glycerol), 3 carbohydrates (sucrose, glucose and fructose) and 12 organic acids (gluconic, lactic, malic, tartaric, oxalic, fumaric, citric and isocitric) were used to optimize chromatographic conditions (concentration gradient and 3 types of column) and the studied isotopic range (-32.28 to -10.65‰) corresponds to the values found in food products. Optimum chromatographic conditions are found using an IonPac AS15, an elution flow rate of 0.3mLmin(-1) and a linear concentration gradient from 2 to 76mM (rate 21mMmin(-1)). Comparison between δ(13)C value individually obtained for each compound with the coupling IRMS and elemental analyzer, EA-IRMS, and the ones measured on the mixture of compounds by IC-co-IRMS does not reveal any isotope fractionation. Thus, under these experimental conditions, IC-co-IRMS results are accurate and reproducible. This new coupling was tested on two food matrices, an orange juice and a sweet wine. Some optimization is necessary as the concentration range between sugars and organic acids is too large: an increase in the filament intensity of the IRMS is necessary to simultaneously detect the two compound families. These first attempts confirm the good results obtained on synthetic solutions and the strong potential of the coupling IC-co-IRMS in food authentication area. Copyright © 2013 Elsevier B.V. All rights reserved.

Multi-isotope imaging mass spectrometry quantifies stem cell division and metabolism.

Science.gov (United States)

Steinhauser, Matthew L; Bailey, Andrew P; Senyo, Samuel E; Guillermier, Christelle; Perlstein, Todd S; Gould, Alex P; Lee, Richard T; Lechene, Claude P

2012-01-15

Mass spectrometry with stable isotope labels has been seminal in discovering the dynamic state of living matter, but is limited to bulk tissues or cells. We developed multi-isotope imaging mass spectrometry (MIMS) that allowed us to view and measure stable isotope incorporation with submicrometre resolution. Here we apply MIMS to diverse organisms, including Drosophila, mice and humans. We test the 'immortal strand hypothesis', which predicts that during asymmetric stem cell division chromosomes containing older template DNA are segregated to the daughter destined to remain a stem cell, thus insuring lifetime genetic stability. After labelling mice with (15)N-thymidine from gestation until post-natal week 8, we find no (15)N label retention by dividing small intestinal crypt cells after a four-week chase. In adult mice administered (15)N-thymidine pulse-chase, we find that proliferating crypt cells dilute the (15)N label, consistent with random strand segregation. We demonstrate the broad utility of MIMS with proof-of-principle studies of lipid turnover in Drosophila and translation to the human haematopoietic system. These studies show that MIMS provides high-resolution quantification of stable isotope labels that cannot be obtained using other techniques and that is broadly applicable to biological and medical research.

Pre-column dilution large volume injection ultra-high performance liquid chromatography-tandem mass spectrometry for the analysis of multi-class pesticides in cabbages.

Science.gov (United States)

Zhong, Qisheng; Shen, Lingling; Liu, Jiaqi; Yu, Dianbao; Li, Siming; Yao, Jinting; Zhan, Song; Huang, Taohong; Hashi, Yuki; Kawano, Shin-ichi; Liu, Zhaofeng; Zhou, Ting

2016-04-15

Pre-column dilution large volume injection (PD-LVI), a novel sample injection technique for reverse phase ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS), was developed in this study. The PD-LVI UHPLC-MS/MS system was designed by slightly modifying the commercial UHPLC-MS/MS equipment with a mixer chamber. During the procedure of PD-LVI, sample solution of 200μL was directly carried by the organic mobile phase to the mixer and diluted with the aqueous mobile phase. After the mixture was introduced to the UHPLC column in a mobile phase of acetonitrile-water (15/85, v/v), the target analytes were stacked on the head of the column until following separation. Using QuEChERS extraction, no additional steps such as solvent evaporation or residue redissolution were needed before injection. The features of PD-LVI UHPLC-MS/MS system were systematically investigated, including the injection volume, the mixer volume, the precondition time and the gradient elution. The efficiency of this approach was demonstrated by direct analysis of 24 pesticides in cabbages. Under the optimized conditions, low limits of detection (0.00074-0.8 ng/kg) were obtained. The recoveries were in the range of 63.3-109% with relative standard deviations less than 8.1%. Compared with common UHPLC-MS/MS technique, PD-LVI UHPLC-MS/MS showed significant advantages such as excellent sensitivity and reliability. The mechanism of PD-LVI was demonstrated to be based on the column-head stacking effect with pre-column dilution. Based on the results, PD-LVI as a simple and effective sample injection technique of reverse phase UHPLC-MS/MS for the analysis of trace analytes in complex samples showed a great promising prospect. Copyright © 2016 Elsevier B.V. All rights reserved.

A field survey of metal binding to metallothionein and other cytosolic ligands in liver of eels using an on-line isotope dilution method in combination with size exclusion (SE) high pressure liquid chromatography (HPLC) coupled to Inductively Coupled Plasma time-of-flight Mass Spectrometry (ICP-TOFMS).

Science.gov (United States)

Van Campenhout, Karen; Goenaga Infante, Heidi; Goemans, Geert; Belpaire, Claude; Adams, Freddy; Blust, Ronny; Bervoets, Lieven

2008-05-15

The effect of metal exposure on the accumulation and cytosolic speciation of metals in livers of wild populations of European eel with special emphasis on metallothioneins (MT) was studied. Four sampling sites in Flanders showing different degrees of heavy metal contamination were selected for this purpose. An on-line isotope dilution method in combination with size exclusion (SE) high pressure liquid chromatography (HPLC) coupled to Inductively Coupled Plasma time-of-flight Mass Spectrometry (ICP-TOFMS) was used to study the cytosolic speciation of the metals. The distribution of the metals Cd, Cu, Ni, Pb and Zn among cytosolic fractions displayed strong differences. The cytosolic concentration of Cd, Ni and Pb increased proportionally with the total liver levels. However, the cytosolic concentrations of Cu and Zn only increased above a certain liver tissue threshold level. Cd, Cu and Zn, but not Pb and Ni, were largely associated with the MT pool in correspondence with the environmental exposure and liver tissue concentrations. Most of the Pb and Ni and a considerable fraction of Cu and Zn, but not Cd, were associated to High Molecular Weight (HMW) fractions. The relative importance of the Cu and Zn in the HMW fraction decreased with increasing contamination levels while the MT pool became progressively more important. The close relationship between the cytosolic metal load and the total MT levels or the metals bound on the MT pool indicates that the metals, rather than other stress factors, are the major factor determining MT induction.

Development of chemical isotope labeling liquid chromatography mass spectrometry for silkworm hemolymph metabolomics

International Nuclear Information System (INIS)

Shen, Weifeng; Han, Wei; Li, Yunong; Meng, Zhiqi; Cai, Leiming; Li, Liang

2016-01-01

Silkworm (Bombyx mori) is a very useful target insect for evaluation of endocrine disruptor chemicals (EDCs) due to mature breeding techniques, complete endocrine system and broad basic knowledge on developmental biology. Comparative metabolomics of silkworms with and without EDC exposure offers another dimension of studying EDCs. In this work, we report a workflow on metabolomic profiling of silkworm hemolymph based on high-performance chemical isotope labeling (CIL) liquid chromatography mass spectrometry (LC-MS) and demonstrate its application in studying the metabolic changes associated with the pesticide dichlorodiphenyltrichloroethane (DDT) exposure in silkworm. Hemolymph samples were taken from mature silkworms after growing on diet that contained DDT at four different concentrations (1, 0.1, 0.01, 0.001 ppm) as well as on diet without DDT as controls. They were subjected to differential "1"2C-/"1"3C-dansyl labeling of the amine/phenol submetabolome, LC-UV quantification of the total amount of labeled metabolites for sample normalization, and LC-MS detection and relative quantification of individual metabolites in comparative samples. The total concentration of labeled metabolites did not show any significant change between four DDT-treatment groups and one control group. Multivariate statistical analysis of the metabolome data set showed that there was a distinct metabolomic separation between the five groups. Out of the 2044 detected peak pairs, 338 and 1471 metabolites have been putatively identified against the HMDB database and the EML library, respectively. 65 metabolites were identified by the dansyl library searching based on the accurate mass and retention time. Among the 65 identified metabolites, 33 positive metabolites had changes of greater than 1.20-fold or less than 0.83-fold in one or more groups with p-value of smaller than 0.05. Several useful biomarkers including serine, methionine, tryptophan, asymmetric dimethylarginine, N

Development of chemical isotope labeling liquid chromatography mass spectrometry for silkworm hemolymph metabolomics

Energy Technology Data Exchange (ETDEWEB)

Shen, Weifeng [Key Laboratory of Detection for Pesticide Residues, Ministry of Agriculture (China); Sericultural Research Institute, Zhejiang Academy of Agricultural Sciences, Hangzhou (China); Han, Wei; Li, Yunong [Department of Chemistry, University of Alberta, Edmonton, Alberta (Canada); Meng, Zhiqi [Sericultural Research Institute, Zhejiang Academy of Agricultural Sciences, Hangzhou (China); Cai, Leiming, E-mail: cailm@mail.zaas.ac.cn [Institute of Quality and Standard for Agro-products, Zhejiang Academy of Agricultural Sciences, Hangzhou (China); Li, Liang, E-mail: Liang.Li@ualberta.ca [Department of Chemistry, University of Alberta, Edmonton, Alberta (Canada)

2016-10-26

Silkworm (Bombyx mori) is a very useful target insect for evaluation of endocrine disruptor chemicals (EDCs) due to mature breeding techniques, complete endocrine system and broad basic knowledge on developmental biology. Comparative metabolomics of silkworms with and without EDC exposure offers another dimension of studying EDCs. In this work, we report a workflow on metabolomic profiling of silkworm hemolymph based on high-performance chemical isotope labeling (CIL) liquid chromatography mass spectrometry (LC-MS) and demonstrate its application in studying the metabolic changes associated with the pesticide dichlorodiphenyltrichloroethane (DDT) exposure in silkworm. Hemolymph samples were taken from mature silkworms after growing on diet that contained DDT at four different concentrations (1, 0.1, 0.01, 0.001 ppm) as well as on diet without DDT as controls. They were subjected to differential {sup 12}C-/{sup 13}C-dansyl labeling of the amine/phenol submetabolome, LC-UV quantification of the total amount of labeled metabolites for sample normalization, and LC-MS detection and relative quantification of individual metabolites in comparative samples. The total concentration of labeled metabolites did not show any significant change between four DDT-treatment groups and one control group. Multivariate statistical analysis of the metabolome data set showed that there was a distinct metabolomic separation between the five groups. Out of the 2044 detected peak pairs, 338 and 1471 metabolites have been putatively identified against the HMDB database and the EML library, respectively. 65 metabolites were identified by the dansyl library searching based on the accurate mass and retention time. Among the 65 identified metabolites, 33 positive metabolites had changes of greater than 1.20-fold or less than 0.83-fold in one or more groups with p-value of smaller than 0.05. Several useful biomarkers including serine, methionine, tryptophan, asymmetric dimethylarginine, N

Elemental labelling combined with liquid chromatography inductively coupled plasma mass spectrometry for quantification of biomolecules: A review

International Nuclear Information System (INIS)

Kretschy, Daniela; Koellensperger, Gunda; Hann, Stephan

2012-01-01

Highlights: ► Survey of bio-analytical approaches utilizing biomolecule labelling. ► Detailed discussion of methodology and chemistry of elemental labelling. ► Biomedical and bio-analytical applications of elemental labelling. ► FI-ICP-MS and LC–ICP-MS for quantification of elemental labelled biomolecules. ► Review of selected applications. - Abstract: This article reviews novel quantification concepts where elemental labelling is combined with flow injection inductively coupled plasma mass spectrometry (FI-ICP-MS) or liquid chromatography inductively coupled plasma mass spectrometry (LC–ICP-MS), and employed for quantification of biomolecules such as proteins, peptides and related molecules in challenging sample matrices. In the first sections an overview on general aspects of biomolecule quantification, as well as of labelling will be presented emphasizing the potential, which lies in such methodological approaches. In this context, ICP-MS as detector provides high sensitivity, selectivity and robustness in biological samples and offers the capability for multiplexing and isotope dilution mass spectrometry (IDMS). Fundamental methodology of elemental labelling will be highlighted and analytical, as well as biomedical applications will be presented. A special focus will lie on established applications underlining benefits and bottlenecks of such approaches for the implementation in real life analysis. Key research made in this field will be summarized and a perspective for future developments including sophisticated and innovative applications will given.

[Application of liquid chromatography-high resolution mass spectrometry in toxicological screening].

Science.gov (United States)

Li, Xiao-Wen; Shen, Bao-Hua; Zhuo, Xian-Yi

2011-10-01

Due to the diversity of toxicologically relevant substances, the uncertainty of target compounds and the specificity of samples, toxicological screening techniques have always been valued by the forensic toxicologists. Depending on its powerful separation ability, superhigh resolution and accurate mass measurement, combined with the two levels spectrum database matching and abundance ratio of isotope ion, the liquid chromatography-high resolution mass spectrometry (LC-HRMS) analyzers have increasingly advantage in screening and identification of chemical compound. This review focuses on the applications of LC-HRMS in screening and identification of drug-of-abuse, prescription drugs, pesticide and stimulant. The prospect of LC-HRMS in forensic toxicology analysis is also included.

Precision of glucose measurements in control sera by isotope dilution/mass spectrometry: proposed definitive method compared with a reference method

International Nuclear Information System (INIS)

Pelletier, O.; Arratoon, C.

1987-01-01

This improved isotope-dilution gas chromatographic/mass spectrometric (GC/MS) method, in which [ 13 C]glucose is the internal standard, meets the requirements of a Definitive Method. In a first study with five reconstituted lyophilized sera, a nested analysis of variance of GC/MS values indicated considerable among-vial variation. The CV for 32 measurements per serum ranged from 0.5 to 0.9%. However, concentration and uncertainty values (mmol/L per gram of serum) assigned to one serum by the NBS Definitive Method (7.56 +/- 0.28) were practically identical to those obtained with the proposed method (7.57 +/- 0.20). In the second study, we used twice more [ 13 C]glucose diluent to assay four serum pools and two lyophilized sera. The CV ranged from 0.26 to 0.5% for the serum pools and from 0.28 to 0.59% for the lyophilized sera. In comparison, results by the hexokinase/glucose-6-phosphate dehydrogenase reference method agreed within acceptable limits with those by the Definitive Method but tended to be slightly higher (up to 3%) for lyophilized serum samples or slightly lower (up to 2.5%) for serum pools

Stable isotope labeling – Liquid chromatography/mass spectrometry for quantitative analysis of androgenic and progestagenic steroids

International Nuclear Information System (INIS)

Guo, Ning; Liu, Ping; Ding, Jun; Zheng, Shu-Jian; Yuan, Bi-Feng; Feng, Yu-Qi

2016-01-01

Steroid hormones play important roles in mammal at very low concentrations and are associated with numerous endocrinology and oncology diseases. Therefore, quantitative analysis of steroid hormones can provide crucial information for uncovering underlying mechanisms of steroid hormones related diseases. In the current study, we developed a sensitive method for the detection of steroid hormones (progesterone, dehydroepiandrosterone, testosterone, pregnenolone, 17-hydroxyprogesterone, androstenedione and 17α-hydroxypregnenolone) in body fluids by stable isotope labeling coupled with liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) analysis. In this respect, a pair of isotopes labeling reagents, Girard reagent P (GP) and d_5-Girard reagent P (d_5-GP), were synthesized and utilized to label steroid hormones in follicular fluid samples and steroid hormone standards, respectively. The heavy labeled standards were used as internal standards for quantification to minimize quantitation deviation in MS analysis due to the matrix and ion suppression effects. The ionization efficiencies of steroid hormones were greatly improved by 4–504 folds through the introduction of a permanent charged moiety of quaternary ammonium from GP. Using the developed method, we successfully quantified steroid hormones in human follicular fluid. We found that the contents of testosterone and androstenedione exhibited significant increase while the content of pregnenolone had significant decrease in follicular fluid of polycystic ovarian syndrome (PCOS) patients compared with healthy controls, indicating that these steroid hormones with significant change may contribute to the pathogenesis of PCOS. Taken together, the developed stable isotope labeling coupled LC-ESI-MS/MS analysis demonstrated to be a promising method for the sensitive and accurate determination of steroid hormones, which may facilitate the in-depth investigation of steroid hormones related

Stable isotope labeling – Liquid chromatography/mass spectrometry for quantitative analysis of androgenic and progestagenic steroids

Energy Technology Data Exchange (ETDEWEB)

Guo, Ning; Liu, Ping; Ding, Jun; Zheng, Shu-Jian; Yuan, Bi-Feng; Feng, Yu-Qi, E-mail: yqfeng@whu.edu.cn

2016-01-28

Steroid hormones play important roles in mammal at very low concentrations and are associated with numerous endocrinology and oncology diseases. Therefore, quantitative analysis of steroid hormones can provide crucial information for uncovering underlying mechanisms of steroid hormones related diseases. In the current study, we developed a sensitive method for the detection of steroid hormones (progesterone, dehydroepiandrosterone, testosterone, pregnenolone, 17-hydroxyprogesterone, androstenedione and 17α-hydroxypregnenolone) in body fluids by stable isotope labeling coupled with liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) analysis. In this respect, a pair of isotopes labeling reagents, Girard reagent P (GP) and d{sub 5}-Girard reagent P (d{sub 5}-GP), were synthesized and utilized to label steroid hormones in follicular fluid samples and steroid hormone standards, respectively. The heavy labeled standards were used as internal standards for quantification to minimize quantitation deviation in MS analysis due to the matrix and ion suppression effects. The ionization efficiencies of steroid hormones were greatly improved by 4–504 folds through the introduction of a permanent charged moiety of quaternary ammonium from GP. Using the developed method, we successfully quantified steroid hormones in human follicular fluid. We found that the contents of testosterone and androstenedione exhibited significant increase while the content of pregnenolone had significant decrease in follicular fluid of polycystic ovarian syndrome (PCOS) patients compared with healthy controls, indicating that these steroid hormones with significant change may contribute to the pathogenesis of PCOS. Taken together, the developed stable isotope labeling coupled LC-ESI-MS/MS analysis demonstrated to be a promising method for the sensitive and accurate determination of steroid hormones, which may facilitate the in-depth investigation of steroid hormones

Redox substoichiometry in isotope dilution analysis Pt. 2

International Nuclear Information System (INIS)

Kambara, T.; Suzuki, J.; Yoshioka, H.; Nakajima, N.

1978-01-01

Isotope dilution analysis using the redox substoichiometric principle has been applied to the determination of antimony content in metallic zinc. As the substoichiometric reaction, the oxidation of trivalent to pentavalent antimony with potassium permanganate was used, followed by separation of these species by the BHPA extraction of trivalent antimony. Determination of antimony contents less than 0.5 μg was found to be possible with good accuracy, without separation of zinc ions. The antimony content in a metallic zinc sample was determined to be 19.7+-0.8 ppm, in good agreement with the results obtained by the other analytical methods. (author)

Spectrophotometric-isotope dilution determination of arsenic in soils and rock

Science.gov (United States)

Brown, F.W.; Simon, F.O.; Greenland, L.P.

1975-01-01

Arsenic in soil and rock samples may be determined in part-per-million concentrations using a radiochemical-isotope dilution method. Arsenic in the sample plus added As76 tracer is separated as arsine and determined spectrophotometrically as a molybdenum blue complex. The As76 activity in the absorbing solution allows corrections for chemical losses. A lower limit of 1 ppm is determinate in a 0.5-g sample.

Analysis of urinary 8-isoprostane as an oxidative stress biomarker by stable isotope dilution using automated online in-tube solid-phase microextraction coupled with liquid chromatography-tandem mass spectrometry.

Science.gov (United States)

Mizuno, Keisuke; Kataoka, Hiroyuki

2015-08-10

We have developed a simple and sensitive method for the determination of the oxidative stress biomarker 8-isoprostane (8-IP) in human urine by automated online in-tube solid-phase microextraction (SPME) coupled with liquid chromatography-tandem mass spectrometry (LC-MS/MS) using a Zorbax Eclipse XDB-8 column and 0.1% formic acid/methanol (25/75, v/v) as a mobile phase. Electrospray MS/MS for 8-IP was performed on an API 4000 triple quadruple mass spectrometer in negative ion mode. The optimum in-tube SPME conditions were 20 draw/eject cycles with a sample size of 40 μL using a Carboxen 1006 PLOT capillary column for the extraction. The extracted compounds were easily desorbed from the capillary by passage of the mobile phase, and no carryover was observed. Total analysis time of this method including online extraction and analysis was about 30 min for each sample. The in-tube SPME LC-MS/MS method showed good linearity in the concentration range of 20-1000 pg/mL with a correlation coefficient r = 0.9999 for 8-IP using a stable isotope-labeled internal standard, 8-IP-d4. The detection limit of 8-IP was 3.3 pg/mL and the proposed method showed 42-fold higher sensitivity than the direct injection method. The intra-day and inter-day precisions (relative standard deviations) were below 5.0% and 8.5% (n = 5), respectively. This method was applied successfully to the analysis of urine samples without pretreatment or interference peaks. The recovery rates of 8-IP spiked into urine samples were above 92%. This method is useful for assessing the effects of oxidative stress and antioxidant intake. Copyright © 2015 Elsevier B.V. All rights reserved.

Using GC-combustion isotope ratio mass spectrometry for confirming steroid administration from urinary metabolites in humans and animals

International Nuclear Information System (INIS)

Phillips, A.; Churchman, D.; Davis, S.

2000-01-01

Gas chromatography-combustion-isotope ratio mass spectrometry (GC-C-IRMS) was used to study the incorporation of exogenous testosterone enanthate into excreted urinary 5α- and 5β-androstane-3α, 17β-diols

Carbon isotopic analysis of atmospheric methane by isotope-ratio-monitoring gas chromatography-mass spectrometry

Science.gov (United States)

Merritt, Dawn A.; Hayes, J. M.; Des Marais, David J.

1995-01-01

Less than 15 min are required for the determination of delta C(sub PDB)-13 with a precision of 0.2 ppt(1 sigma, single measurement) in 5-mL samples of air containing CH4 at natural levels (1.7 ppm). An analytical system including a sample-introduction unit incorporating a preparative gas chromatograph (GC) column for separation of CH4 from N2, O2, and Ar is described. The 15-min procedure includes time for operation of that system, high-resolution chromatographic separation of the CH4, on-line combustion and purification of the products, and isotopic calibration. Analyses of standards demonstrate that systematic errors are absent and that there is no dependence of observed values of delta on sample size. For samples containing 100 ppm or more CH4, preconcentration is not required and the analysis time is less than 5 min. The system utilizes a commercially available, high-sensitivity isotope-ratio mass spectrometer. For optimal conditions of smaple handling and combustion, performance of the system is within a factor of 2 of the shot-noise limit. The potential exists therefore for analysis of samples as small as 15 pmol CH4 with a standard deviation of less than 1 ppt.

A Computational Drug Metabolite Detection Using the Stable Isotopic Mass-Shift Filtering with High Resolution Mass Spectrometry in Pioglitazone and Flurbiprofen

Directory of Open Access Journals (Sweden)

Yohei Miyamoto

2013-09-01

Full Text Available The identification of metabolites in drug discovery is important. At present, radioisotopes and mass spectrometry are both widely used. However, rapid and comprehensive identification is still laborious and difficult. In this study, we developed new analytical software and employed a stable isotope as a tool to identify drug metabolites using mass spectrometry. A deuterium-labeled compound and non-labeled compound were both metabolized in human liver microsomes and analyzed by liquid chromatography/time-of-flight mass spectrometry (LC-TOF-MS. We computationally aligned two different MS data sets and filtered ions having a specific mass-shift equal to masses of labeled isotopes between those data using our own software. For pioglitazone and flurbiprofen, eight and four metabolites, respectively, were identified with calculations of mass and formulas and chemical structural fragmentation analysis. With high resolution MS, the approach became more accurate. The approach detected two unexpected metabolites in pioglitazone, i.e., the hydroxypropanamide form and the aldehyde hydrolysis form, which other approaches such as metabolite-biotransformation list matching and mass defect filtering could not detect. We demonstrated that the approach using computational alignment and stable isotopic mass-shift filtering has the ability to identify drug metabolites and is useful in drug discovery.

A 233U/236U/242Pu/244Pu spike for isotopic and isotope dilution analysis by mass spectrometry with internal calibration

International Nuclear Information System (INIS)

Stepanov, A.; Belyaev, B.; Buljanitsa, L.

1989-11-01

The Khlopin Radium Institute prepared on behalf of the IAEA a synthetic mixture of 233 U, 236 U, 242 Pu and 244 Pu isotopes. The isotopic composition and elemental concentration of uranium and plutonium were certified on the basis of analyses done by four laboratories of the IAEA Network, using mass spectrometry with internal standardization. The certified values for 233 U/ 236 U ratio and the 236 U chemical concentration have a coefficient of variation of 0.05%. The latter is fixed by the uncertainty in the 235 U/ 238 U ratio of NBS500 used as internal standard. The coefficients of variation of the 244 Pu/ 242 Pu ratio and the 242 Pu chemical concentration are respectively 0.10% and 0.16% and limited by the uncertainty in the 240 Pu/ 239 Pu ratio of NBS947. This four isotope mixture was used as an internal standard as well as a spike, to analyze 30 batches of LWR spent fuel solutions. The repeatability of the mass spectrometric measurements have a coefficient of variation of 0.025% for the uranium concentration, and of 0.039% for the plutonium concentration. The spiking and treatment errors had a coefficient of variation of 0.048%. (author). Refs, figs and tabs

Determination of microquantities of silver in platinum by isotope dilution

International Nuclear Information System (INIS)

Yedinakova, V.; Sladkovska, Y.

1980-01-01

A method is described for determining microquantities of silver in platinum. It is based on isotope dilution by means of substoichiometric extraction of dithizonates with carbon tetrachloride. The determination of silver according to this technique is not interfered by zinc or gold in quantities exceeding the silver content by one order of magnitude nor by a great excess of platinum. In the presence of copper the addition of complexon is necessary. (author)

Simultaneous determination of tyrosine, phenylalanine and deoxyguanosine oxidation products by liquid chromatography-tandem mass spectrometry as non-invasive biomarkers for oxidative damage

NARCIS (Netherlands)

Orhan, Hilmi; Vermeulen, Nico P E; Tump, Cornelis; Zappey, Herman; Meerman, John H N

2004-01-01

We developed an isotope dilution HPLC-atmospheric pressure chemical ionization-tandem mass spectrometry (HPLC-APCI-MS/MS) method for the simultaneous determination of p-tyrosine, phenylalanine, o,o'-dityrosine, m-tyrosine, o-tyrosine, 3-chlorotyrosine and 3-nitrotyrosine and

"Dilute-and-inject" multi-target screening assay for highly polar doping agents using hydrophilic interaction liquid chromatography high resolution/high accuracy mass spectrometry for sports drug testing.

Science.gov (United States)

Görgens, Christian; Guddat, Sven; Orlovius, Anne-Katrin; Sigmund, Gerd; Thomas, Andreas; Thevis, Mario; Schänzer, Wilhelm

2015-07-01

In the field of LC-MS, reversed phase liquid chromatography is the predominant method of choice for the separation of prohibited substances from various classes in sports drug testing. However, highly polar and charged compounds still represent a challenging task in liquid chromatography due to their difficult chromatographic behavior using reversed phase materials. A very promising approach for the separation of hydrophilic compounds is hydrophilic interaction liquid chromatography (HILIC). Despite its great potential and versatile advantages for the separation of highly polar compounds, HILIC is up to now not very common in doping analysis, although most manufacturers offer a variety of HILIC columns in their portfolio. In this study, a novel multi-target approach based on HILIC high resolution/high accuracy mass spectrometry is presented to screen for various polar stimulants, stimulant sulfo-conjugates, glycerol, AICAR, ethyl glucuronide, morphine-3-glucuronide, and myo-inositol trispyrophosphate after direct injection of diluted urine specimens. The usage of an effective online sample cleanup and a zwitterionic HILIC analytical column in combination with a new generation Hybrid Quadrupol-Orbitrap® mass spectrometer enabled the detection of highly polar analytes without any time-consuming hydrolysis or further purification steps, far below the required detection limits. The methodology was fully validated for qualitative and quantitative (AICAR, glycerol) purposes considering the parameters specificity; robustness (rRT  0.99); intra- and inter-day precision at low, medium, and high concentration levels (CV < 20%); limit of detection (stimulants and stimulant sulfo-conjugates < 10 ng/mL; norfenefrine; octopamine < 30 ng/mL; AICAR < 10 ng/mL; glycerol 100 μg/mL; ETG < 100 ng/mL); accuracy (AICAR 103.8-105.5%, glycerol 85.1-98.3% at three concentration levels) and ion suppression/enhancement effects.

Frontal and band displacement chromatography of the hydrogen isotopes on palladium; Chromatographies frontale et de deplacement de bande des isotopes de l'hydrogene sur palladium

Energy Technology Data Exchange (ETDEWEB)

Botter, F; Menes, J; Tistchenko, S; Dirian, G [Commissariat a l' Energie Atomique, Saclay (France). Centre d' Etudes Nucleaires

1964-07-01

As a result of hydrogen isotope separations which we have carried out on supports containing palladium, we believe that we can now make a double contribution, theoretical and experimental, to the work which has already been published in this field. From the fundamental point of view we have developed and studied the validity of a simple model, in our particular case of a separation coefficient {alpha} which is very different to unity. This model, which is of a counter-current isotopic exchange, neglects the longitudinal diffusion in the gas phase and the lateral diffusion in the adsorbed phase and only takes into account the surface resistance to exchange between the phases. It is therefore possible to estimate the efficiency of a chromatography column in terms of the height equivalent of a theoretical plate (HETP). The slight differences observed between the actual chromatograms and the simple model justify both the research undertaken into a more complex model taking into account the diffusion, and the adoption of a simple model for comparing the efficiency of several columns. We describe also a new and simple graphical method for deducing the number of theoretical plates of a column in chromatograms of the frontal and band displacement types. Experimentally we give in particular the criteria for the validity of the model used, the law as a function of the {sup {alpha}}H{sub 2}-HD temperature, the study of the HETP as a function of the various parameters on several palladium containing supports, and the possibilities of an application to preparative chromatography. (authors) [French] Grace aux separations des isotopes de l'hydrogene que nous avons realisees sur masses palladiees, nous pensons apporter aux etudes precedemment publiees dans ce domaine, une double contribution, theorique et experimentale. Du point de vue fondamental, on a developpe et etudie la validite d'un modele simple, dans notre cas particulier d'un coefficient de separation {alpha} tres

Electrochemical separation and isotopic determination of thallium at the nanogram level by surface ionisation mass spectrometry

International Nuclear Information System (INIS)

Arden, J.W.

1983-01-01

A rapid low-blank procedure is described for the co-separation of thallium and lead by sequential cathodic and anodic electrodeposition from natural samples, especially complex natural silicates, for subsequent mass spectrometry. A micro anion-exchange procedure is also described for the separation of thallium and lead. Ion currents of 10 - 10 A can be obtained from 1 ng of thallium. The isotopic composition of 1 ng of thallium can be measured on a Faraday detector with a precision of 0.05-0.1%. The total procedural blank is 3 pg. By using stable isotope dilution, 0.2 ng of thallium can be measured with a precision of 0.6% with only a 2% blank correction. This allows the accurate determination of thallium in natural samples down to concentration levels of about 50 pg g - 1 . The detection limit is 50 fg. This procedure has been applied to meteorites and terrestrial rocks. The stable isotope dilution technique is suitable for geochemical, environmental and toxicological studies requiring a highly sensitive, accurate and precise method for the determination of thallium. (Auth.)

Experimental substantiation of separation techniques of lead and uranium microamounts using isotopic dilution method as control method

International Nuclear Information System (INIS)

Agapova, A.A.; Shcherbinina, N.K.

1983-01-01

Methods,ensuring at low levels of contamination a high degree of lead and uranium microamount separation from solutions of geological samples, have been selected and subjected to the detailed testing. The method of isotope dilution, , combining high accuracy and sensitivity of determinations, is used as the main control methods, is used as the main control method. Using the method, processe es of uranium extpaction are traced, special attention is paid to the detailed description of lead extraction at all the stages of the methods selected. Opera ations of ion exchange for lead and uranium in microcolumns with the Bio-Rad r sin are considered, as well as operations of lead electrolytic separation. The chemical procedures suggested permit to solve one of the main methodical tasks f sample preparation, containing microgram amounts of lead and uranium, for high h-prcision measurement of their isotope composition using mass-spectrometric method

Liquid chromatography mass spectrometry determination of perfluoroalkyl acids in environmental solid extracts after phospholipid removal and on-line turbulent flow chromatography purification.

Science.gov (United States)

Mazzoni, M; Polesello, S; Rusconi, M; Valsecchi, S

2016-07-01

An on-line TFC (Turbulent Flow Chromatography) clean up procedures coupled with UHPLC-MS/MS (Ultra High Performance Liquid Chromatography Mass Spectrometry) multi-residue method was developed for the simultaneous determination of 8 perfluroalkyl carboxylic acids (PFCA, from 5 to 12 carbon atoms) and 3 perfluoroalkyl sulfonic acids (PFSA, from 4 to 8 carbon atoms) in environmental solid matrices. Fast sample preparation procedure was based on a sonication-assisted extraction with acetonitrile. Phospholipids in biological samples were fully removed by an off-line SPE purification before injection, using HybridSPE(®) Phospholipid Ultra cartridges. The development of the on-line TFC clean-up procedure regarded the choice of the stationary phase, the optimization of the mobile phase composition, flow rate and injected volume. The validation of the optimized method included the evaluation of matrix effects, accuracy and reproducibility. Signal suppression in the analysis of fortified extracts ranged from 1 to 60%, and this problem was overcome by using isotopic dilution. Since no certified reference materials were available for PFAS in these matrices, accuracy was evaluated by recoveries on spiked clam samples which were 98-133% for PFCAs and 40-60% for PFSAs. MLDs and MLQs ranged from 0.03 to 0.3ngg(-1) wet weight and from 0.1 to 0.9ngg(-1) wet weight respectively. Repeatability (intra-day precision) and reproducibility (inter-day precision) showed RSD from 3 to 13% and from 4 to 27% respectively. Validated on-line TFC/UHPLC-MS/MS method has been applied for the determination of perfluoroalkyl acids in different solid matrices (sediment, fish, bivalves and bird yolk). Copyright © 2016 Elsevier B.V. All rights reserved.

Vitamin A metabolism, kinetic behavior and utilization: Rationale for the continued development and use of an isotope dilution technique for assessing vitamin A stores in human populations

International Nuclear Information System (INIS)

Green, M.H.

1997-01-01

The paper discusses the applicability of isotope dilution method in general and oral isotope dilution in particular to the assessment of vitamin A status in humans. It also highlights some aspects of vitamin A intake and metabolism as related to isotope dilution method. Areas of methodological research and development in vitamin A research are also proposed

Liquid-chromatography mass spectrometry (LC-MS) of steroid hormone metabolites and its applications

Science.gov (United States)

Penning, Trevor M.; Lee, Seon-Hwa; Jin, Yi; Gutierrez, Alejandro; Blair, Ian A.

2010-01-01

Advances in liquid chromatography-mass spectrometry (LC-MS) can be used to measure steroid hormone metabolites in vitro and in vivo. We find that LC-Electrospray Ionization (ESI)-MS using a LCQ ion trap mass spectrometer in the negative ion mode can be used to monitor the product profile that results from 5α–dihydrotestosterone(DHT)-17β-glucuronide, DHT-17β-sulfate, and tibolone-17β-sulfate reduction catalyzed by human members of the aldo-keto reductase (AKR) 1C subfamily and assign kinetic constants to these reactions. We also developed a stable-isotope dilution LC-electron capture atmospheric pressure chemical ionization (ECAPCI)-MS method for the quantitative analysis of estrone (E1) and its metabolites as pentafluorobenzyl (PFB) derivatives in human plasma in the attomole range. The limit of detection for E1-PFB was 740 attomole on column. Separations can be performed using normal-phase LC because ionization takes place in the gas phase rather than in solution. This permits efficient separation of the regioisomeric 2- and 4-methoxy-E1. The method was validated for the simultaneous analysis of plasma E2 and its metabolites: 2-methoxy-E2, 4-methoxy-E2, 16α-hydroxy-E2, estrone (E1), 2-methoxy-E1, 4-methoxy-EI, and 16α-hydroxy-E1 from 5 pg/mL to 2,000 pg/mL. Our LC-MS methods have sufficient sensitivity to detect steroid hormone levels in prostate and breast tumors and should aid their molecular diagnosis and treatment. PMID:20083198

Isotope dilution-GC-MS/MS analysis of 16 polycyclic aromatic hydrocarbons in selected medicinal herbs used as health food additives.

Science.gov (United States)

Yu, L; Cao, Y; Zhang, J; Cui, Z; Sun, H

2012-01-01

Medicinal herbs have a very important role in health protection and disease control, and have been used in health foods. Polycyclic aromatic hydrocarbons (PAHs) have carcinogenic, biological and mutagenic effects. In this paper, the content of 16 PAHs as representative contaminants in nine Chinese medicinal herbs, as additives for health foods, was investigated in order to ensure food safety from this source. A highly sensitive isotope dilution-gas chromatography-tandem mass spectrometry (ID-GC-MS/MS) method combined with gel permeation chromatography (GPC) and solid-phase extraction (SPE) was developed. Calibration curves showed good linearity for all PAHs (R² > 0.999), and the limit of quantification (LOQ) ranged from 0.42 to 2.7 µg kg⁻¹. Average recoveries for these compounds were in the range of 52.5-117%, 52.6-119% and 81.4-108% at the concentrations of 10, 50 and 250 µg kg⁻¹ with RSD of 1.8-15%, 0.9-15% and 1.0-15%, respectively. The proposed method was used for the analysis of nine Chinese medicinal herbs. Total levels of PAHs varied from 98.2 µg kg⁻¹ (cassia seed) to 2245 µg kg⁻¹ (eucommia bark). The highest level was found for phenanthrene (Phe) in liquorice root (631.3 µg kg⁻¹), indigowoad leaf (551.0 µg kg⁻¹), rose flower (435.2 µg kg⁻¹) and eucommia bark (432.3 µg kg⁻¹). The proposed method could provide a useful basis for safety monitoring of herbs and risk management for PAHs in the health food industry.

Pb and Sr isotope measurements by inductively coupled plasma mass spectrometer: efficient time management for precision improvement

Science.gov (United States)

Monna, F.; Loizeau, J.-L.; Thomas, B. A.; Guéguen, C.; Favarger, P.-Y.

1998-08-01

One of the factors limiting the precision of inductively coupled plasma mass spectrometry is the counting statistics, which depend upon acquisition time and ion fluxes. In the present study, the precision of the isotopic measurements of Pb and Sr is examined. The time of measurement is optimally shared for each isotope, using a mathematical simulation, to provide the lowest theoretical analytical error. Different algorithms of mass bias correction are also taken into account and evaluated in term of improvement of overall precision. Several experiments allow a comparison of real conditions with theory. The present method significantly improves the precision, regardless of the instrument used. However, this benefit is more important for equipment which originally yields a precision close to that predicted by counting statistics. Additionally, the procedure is flexible enough to be easily adapted to other problems, such as isotopic dilution.

Simultaneous detection of six urinary pteridines and creatinine by high-performance liquid chromatography-tandem mass spectrometry for clinical breast cancer detection.

Science.gov (United States)

Burton, Casey; Shi, Honglan; Ma, Yinfa

2013-11-19

Recent preliminary studies have implicated urinary pteridines as candidate biomarkers in a growing number of malignancies including breast cancer. While the developments of capillary electrophoresis-laser induced fluorescence (CE-LIF), high performance liquid chromatography (HPLC), and liquid chromatography-mass spectroscopy (LC-MS) pteridine urinalyses among others have helped to enable these findings, limitations including poor pteridine specificity, asynchronous or nonexistent renal dilution normalization, and a lack of information regarding adduct formation in mass spectrometry techniques utilizing electrospray ionization (ESI) have prevented application of these techniques to a larger clinical setting. In this study, a simple, rapid, specific, and sensitive high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method has been developed and optimized for simultaneous detection of six pteridines previously implicated in breast cancer and creatinine as a renal dilution factor in urine. In addition, this study reports cationic adduct formation of urinary pteridines under ESI-positive ionization for the first time. This newly developed technique separates and detects the following six urinary pteridines: 6-biopterin, 6-hydroxymethylpterin, d-neopterin, pterin, isoxanthopterin, and xanthopterin, as well as creatinine. The method detection limit for the pteridines is between 0.025 and 0.5 μg/L, and for creatinine, it is 0.15 μg/L. The method was also validated by spiked recoveries (81-105%), reproducibility (RSD: 1-6%), and application to 25 real urine samples from breast cancer positive and negative samples through a double-blind study. The proposed technique was finally compared directly with a previously reported CE-LIF technique, concluding that additional or alternative renal dilution factors are needed for proper investigation of urinary pteridines as breast cancer biomarkers.

Stable carbon and hydrogen isotope analysis of methyl tert-butyl ether and tert-amyl methyl ether by purge and trap-gas chromatography-isotope ratio mass spectrometry: method evaluation and application.

Science.gov (United States)

Kujawinski, Dorothea M; Stephan, Manuel; Jochmann, Maik A; Krajenke, Karen; Haas, Joe; Schmidt, Torsten C

2010-01-01

In order to monitor the behaviour of contaminants in the aqueous environment effective enrichment techniques often have to be employed due to their low concentrations. In this work a robust and sensitive purge and trap-gas chromatography-isotope ratio mass spectrometry method for carbon and hydrogen isotope analysis of fuel oxygenates in water is presented. The method evaluation included the determination of method detection limits, accuracy and reproducibility of deltaD and delta(13)C values. Lowest concentrations at which reliable delta(13)C values could be determined were 5 microg L(-1) and 28 microg L(-1) for TAME and MTBE, respectively. Stable deltaD values for MTBE and TAME could be achieved for concentrations as low as 25 and 50 microg L(-1). Good long-term reproducibility of delta(13)C and deltaD values was obtained for all target compounds. But deltaD values varying more than 5 per thousand were observed using different thermal conversion tubes. Thus, a correction of deltaD values in the analysis of groundwater samples was necessary to guarantee comparability of the results. The applicability of this method was shown by the analysis of groundwater samples from a gasoline contaminated site. By two dimensional isotope analysis two locations within this site were identified at which anaerobic and aerobic degradation of methyl tert-butyl ether occurred.

Determination of carbon isotope ratios for honey samples by means of a liquid chromatography/isotope ratio mass spectrometry system coupled with a post-column pump.

Science.gov (United States)

Kawashima, Hiroto; Suto, Momoka; Suto, Nana

2018-05-20

Liquid chromatography/isotope ratio mass spectrometry (LC/IRMS) has been used to authenticate and trace products such as honey, wine, and lemon juice, and compounds such as caffeine and pesticides. However, LC/IRMS has several disadvantages, including the high cost of the CO 2 membrane and blocking by solidified sodium persulfate. Here, we developed an improved system for determining carbon isotope ratios by LC/IRMS. The main improvement was the use of a post-column pump. Using the improved system, we determined δ 13 C values for glucose with high accuracy and precision (0.1‰ and 0.1‰, respectively; n = 3). The glucose, fructose, disaccharide, trisaccharide, and organic acid constituents of the honey samples were analyzed by LC/IRMS. The δ 13 C values for glucose, fructose, disaccharides, trisaccharides, and organic acids ranged from -27.0 to -24.2‰, -26.8 to -24.0‰, -28.8 to -24.0‰, -27.8 to -22.8‰, and -30.6 to -27.4‰, respectively. The analysis time was 1/3-1/2 the times required for analysis by previously reported methods. The column flow rate could be arbitrarily adjusted with the post-column pump. We applied the improved method to 26 commercial honey samples. Our results can be expected to be useful for other researchers who use LC/IRMS. This article is protected by copyright. All rights reserved.

Determination of acrylamide in Chinese traditional carbohydrate-rich foods using gas chromatography with micro-electron capture detector and isotope dilution liquid chromatography combined with electrospray ionization tandem mass spectrometry

International Nuclear Information System (INIS)

Zhang Yu; Ren Yiping; Zhao Hangmei; Zhang Ying

2007-01-01

The present study developed two analytical methods for quantification of acrylamide in complex food matrixes, such as Chinese traditional carbohydrate-rich foods. One is based on derivatization with potassium bromate and potassium bromide without clean-up prior to gas chromatography with micro-electron capture detector (GC-MECD). Alternatively, the underivatized acrylamide was detected by high-performance liquid chromatography coupled to quadrupole tandem mass spectrometry (HPLC-MS/MS) in the positive electrospray ionization mode. For both methods, the Chinese carbohydrate-rich samples were homogenized, defatted with petroleum ether and extracted with aqueous solution of sodium chloride. Recovery rates for acrylamide from spiked Chinese style foods with the spiking level of 50, 500 and 1000 μg kg -1 were in the range of 79-93% for the GC-MECD including derivatization and 84-97% for the HPLC-MS/MS method. Typical quantification limits of the HPLC-MSMS method were 4 μg kg -1 for acrylamide. The GC-MECD method achieved quantification limits of 10 μg kg -1 in Chinese style foods. Thirty-eight Chinese traditional foods purchased from different manufacturers were analyzed and compared with four Western style foods. Acrylamide contaminant was found in all of samples at the concentration up to 771.1 and 734.5 μg kg -1 detected by the GC and HPLC method, respectively. The concentrations determined with the two different quantitative methods corresponded well with each other. A convenient and fast pretreatment procedure will be optimized in order to satisfy further investigation of hundreds of samples

Differentiation of wood-derived vanillin from synthetic vanillin in distillates using gas chromatography/combustion/isotope ratio mass spectrometry for δ13 C analysis.

Science.gov (United States)

van Leeuwen, Katryna A; Prenzler, Paul D; Ryan, Danielle; Paolini, Mauro; Camin, Federica

2018-02-28

Typical storage in oak barrels releases in distillates different degradation products such as vanillin, which play an important role in flavour and aroma. The addition of vanillin, as well as other aroma compounds, of different origin is prohibited by European laws. As vanillin samples from different sources have different δ 13 C values, the δ 13 C value could be used to determine whether the vanillin is authentic (lignin-derived), or if it has been added from another source (e.g. synthetic). The δ 13 C values for vanillin derived from different sources, including natural, synthetic and tannins, were measured by gas chromatography/combustion/isotope ratio mass spectrometry (GC/C/IRMS), after diethyl ether addition and/or ethanol dilution. A method for analysing vanillin in distillates after dichloromethane extraction was developed. Tests were undertaken to prove the reliability, reproducibility and accuracy of the method with standards and samples. Distillate samples were run to measure the δ 13 C values of vanillin and to compare them with values for other sources of vanillin. δ 13 C values were determined for: natural vanillin extracts (-21.0 to -19.3‰, 16 samples); vanillin ex-lignin (-28.2‰, 1 sample); and synthetic vanillin (-32.6 to -29.3‰, 7 samples). Seventeen tannin samples were found to have δ 13 C values of -29.5 to -26.7‰, which were significantly different (p distillates (-28.9 to -25.7‰) were mainly in the tannin range, although one spirit (-32.5‰) was found to contain synthetic vanillin. The results show that synthetic vanillin added to a distillate could be differentiated from vanillin derived from oak barrels by their respective δ 13 C values. The GC/C/IRMS method could be a useful tool in the determination of adulteration of distillates. Copyright © 2017 John Wiley & Sons, Ltd.

Atomic masses of rare-earth isotopes

International Nuclear Information System (INIS)

Schmidt-Ott, W.D.; Kantus, R.; Runte, E.

1981-01-01

A survey is given of decay energies of rare-earth isotopes measured in electron-capture decay by relative Psub(K) ratios, ECsub(K)/β + , and EC/β + ratios. Atomic masses of A = 147 isotopes and of 146 Gd and 148 Dy were derived. The masses of these isotopes and of α-decaying precessors are compared with predictions of current mass formulae. The subshell closure at Z = 64 is shown for N = 82, and 84 isotones. (orig.)

Analysis of glycosaminoglycans in cerebrospinal fluid from patients with mucopolysaccharidoses by isotope-dilution ultra-performance liquid chromatography-tandem mass spectrometry.

Science.gov (United States)

Zhang, Haoyue; Young, Sarah P; Auray-Blais, Christiane; Orchard, Paul J; Tolar, Jakub; Millington, David S

2011-07-01

New therapies for the treatment of mucopolysaccharidoses that target the brain, including intrathecal enzyme replacement, are being explored. Quantitative analysis of the glycosaminoglycans (GAGs) that accumulate in these disorders is required to assess the disease burden and monitor the effect of therapy in affected patients. Because current methods lack the required limit of quantification and specificity to analyze GAGs in small volumes of cerebrospinal fluid (CSF), we developed a method based on ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Samples of CSF (25 μL) were evaporated to dryness and subjected to methanolysis. The GAGs were degraded to uronic acid-N-acetylhexosamine dimers and mixed with internal standards derived from deuteriomethanolysis of GAG standards. Specific dimers derived from heparan, dermatan and chondroitin sulfates (HS, DS and CS) were separated by UPLC and analyzed by electrospray ionization MS/MS using selected reaction monitoring for each targeted GAG product and its corresponding internal standard. CSF from control pediatric subjects (n = 22) contained <0.38 mg/L HS, 0.26 mg/L DS, and 2.8 mg/L CS, whereas CSF from patients with Hurler syndrome (n = 7) contained concentrations of DS and HS that were at least 6-fold greater than the upper control limits. These concentrations were reduced by 17.5% to 82.5% after allogeneic transplantation and treatment with intrathecal and intravenous enzyme replacement therapy. The method described here has potential value in monitoring patients with mucopolysaccharidoses receiving treatment targeted to the brain.

Gas chromatography: mass selective detector

International Nuclear Information System (INIS)

Lapinskas, R.

1988-01-01

The mechanism of mass spectrometry technique directed for detecting molecular structures is described, with some considerations about its operational features. This mass spectrometer is used as a gas chromatography detector. (author)

Calcium Isotope Analysis by Mass Spectrometry

Science.gov (United States)

Boulyga, S.; Richter, S.

2010-12-01

The variations in the isotopic composition of calcium caused by fractionation in heterogeneous systems and by nuclear reactions can provide insight into numerous biological, geological, and cosmic processes, and therefore isotopic analysis finds a wide spectrum of applications in cosmo- and geochemistry, paleoclimatic, nutritional, and biomedical studies. The measurement of calcium isotopic abundances in natural samples has challenged the analysts for more than three decades. Practically all Ca isotopes suffer from significant isobaric interferences, whereas low-abundant isotopes can be particularly affected by neighboring major isotopes. The extent of natural variations of stable isotopes appears to be relatively limited, and highly precise techniques are required to resolve isotopic effects. Isotope fractionation during sample preparation and measurements and instrumental mass bias can significantly exceed small isotope abundance variations in samples, which have to be investigated. Not surprisingly, a TIMS procedure developed by Russell et al. (Russell et al., 1978. Geochim Cosmochim Acta 42: 1075-1090) for Ca isotope measurements was considered as revolutionary for isotopic measurements in general, and that approach is used nowadays (with small modifications) for practically all isotopic systems and with different mass spectrometric techniques. Nevertheless, despite several decades of calcium research and corresponding development of mass spectrometers, the available precision and accuracy is still not always sufficient to achieve the challenging goals. This presentation discusses figures of merits of presently used analytical methods and instrumentation, and attempts to critically assess their limitations. Additionally, the availability of Ca isotope reference materials will be discussed.

Critical mass variation of 239Pu with water dilution

International Nuclear Information System (INIS)

Pearlstein, S.

1996-01-01

The critical mass of an unreflected solid sphere of 239 Pu is ∼ 10 kg. The increase in critical mass observed for small water dilutions of unreflected 239 Pu spheres is paradoxical. Introducing small amounts of water uniformly throughout the sphere increases the spherical volume containing the same amount of 239 Pu as the critical solid sphere. The increase in radius decreases the surface-to-volume ratio of the sphere, which has the effect to first order of decreasing the neutron leakage, which is proportional to the surface, relative to the fissions, which are proportional to the volume. The reduction in neutron leakage is expected to reduce the critical mass, but instead, the critical mass is observed to increase. It is discussed how changes in the fast neutron spectrum with corresponding changes in the nuclear parameters result in an increase in critical mass for small water dilutions

Candidate processes for diluting the 235U isotope in weapons-capable highly enriched uranium

International Nuclear Information System (INIS)

Snider, J.D.

1996-02-01

The United States Department of Energy (DOE) is evaluating options for rendering its surplus inventories of highly enriched uranium (HEU) incapable of being used to produce nuclear weapons. Weapons-capable HEU was earlier produced by enriching uranium in the fissile 235 U isotope from its natural occurring 0.71 percent isotopic concentration to at least 20 percent isotopic concentration. Now, by diluting its concentration of the fissile 235 U isotope in a uranium blending process, the weapons capability of HEU can be eliminated in a manner that is reversible only through isotope enrichment, and therefore, highly resistant to proliferation. To the extent that can be economically and technically justified, the down-blended uranium product will be made suitable for use as commercial reactor fuel. Such down-blended uranium product can also be disposed of as waste if chemical or isotopic impurities preclude its use as reactor fuel

Selection of mode for the measurement of lead isotope ratios by inductively coupled plasma mass spectrometry and its application to milk powder analysis

International Nuclear Information System (INIS)

Dean, J.R.; Ebdon, L.; Massey, R.

1987-01-01

An investigation into the selection of the optimum mode for the measurement of isotope ratios in inductively coupled plasma mass spectrometry (ICP-MS) is reported, with particular reference to lead isotope ratios. Variation in the accuracy and precision achievable using the measurement modes of scanning and peak jumping are discussed. It is concluded that if sufficient sample and time are available, scanning gives best accuracy and precision. Isotope dilution analysis (IDA) has been applied to the measurement of the lead content of two dried milk powders of Australian and European origin introduced as slurries into ICP-MS. Differences in the lead isotope ratios in the two milk powders were investigated and the total lead content determined by IDA. Isotope dilution analysis permitted accurate data to be obtained with an RSD of 4.2% or milk powder containing less than 30 ng g -1 of lead. The ICP-MS technique is confirmed as a useful tool for IDA. (author)

Inter-laboratory comparison of elemental analysis and gas chromatography combustion isotope ratio mass spectrometry (GC-C-IRMS). Part I: delta13C measurements of selected compounds for the development of an isotopic Grob-test.

Science.gov (United States)

Serra, F; Janeiro, A; Calderone, G; Rojas, J M Moreno; Rhodes, C; Gonthier, L A; Martin, F; Lees, M; Mosandl, A; Sewenig, S; Hener, U; Henriques, B; Ramalho, L; Reniero, F; Teixeira, A J; Guillou, C

2007-03-01

This study was directed towards investigating suitable compounds to be used as stable isotope reference materials for gas chromatography combustion isotope ratio mass spectrometry (GC-C-IRMS) calibration. Several compounds were selected from those used in the 'Grob-test' mixture. Oxygen- and nitrogen-containing substances were added to these compounds to allow the mixture to be used as a possible multi-isotopic calibration tool for 2H/1H, 13C/12C, 15N/14N and 18O/16O ratio determinations. In this paper we present the results of delta13C measurements performed by the consortium of the five laboratories taking part in this inter-calibration exercise. All the compounds were individually assessed for homogeneity, short-term stability and long-term stability by means of EA-IRMS, as required by the bureau communitaire de reference (BCR) Guide for Production of Certified Reference Materials. The results were compared then with the GC-C-IRMS measurements using both polar and non-polar columns, and the final mixture of selected compounds underwent a further certification exercise assessing limits of accuracy and reproducibility under specified GC-C-IRMS conditions. Copyright 2007 John Wiley & Sons, Ltd.

Isotopic and chemical dilution effects on the vibrational relaxation rate of some totally symmetric motions of liquid acetonitrile

International Nuclear Information System (INIS)

Marri, E.; Morresi, A.; Paliani, G.; Cataliotti, R.S.; Giorgini, M.G.

1999-01-01

The vibrational dephasing of the ν 1 (C-H, C-D stretching) and ν 3 (C-H, C-D bending) symmetric motions of liquid acetonitrile in its light and fully deuterated forms has been studied in the frame of the vibrational time correlation functions obtained as Fourier transforms of the isotropic Raman spectral distributions and interpreted within the Kubo theory. In addition, the experimental isotropic profiles have been analysed within the bandshape approach formulated by analytical Fourier transformation of the Kubo vibrational time correlation functions in order to derive the relaxation parameters in the frequency domain. The effects of the isotopic (CH 3 CN/CD 3 CN and vice versa) and chemical (CCl 4 ) dilution on the bandshapes and on the vibrational relaxation parameters have been studied. It was observed that the decay rate of ν 1 mode is insensitive to the isotopic dilution but varies appreciably with chemical (CCl 4 ) dilution. The vibrational dephasing of ν 3 mode is qualitatively, but not quantitatively, affected in the same way by chemical dilution and shows a slower modulation regime than that exhibited by the stretching mode. Unlikely from the latter, the ν 3 mode results are slightly affected by the isotopic dilution. Phase relaxation mechanisms of these two motions of acetonitrile in the liquid state are proposed on the basis of these data, and a comparison is made with the results earlier published. (Copyright (c) 1999 Elsevier Science B.V., Amsterdam. All rights reserved.)

Determination of traces of iridium with thiodibenzoylmethane by substoichiometric isotope dilution analysis

International Nuclear Information System (INIS)

Roebisch, G.; Bansse, W.; Ludwig, E.

1980-01-01

Iridium(III or IV) reacts with thiodibenzoylmethane on heating at pH 6 to form a 1:3 complex, which can be concentrated by extraction into chloroform. Based on this reaction, a reproducible, selective determination of iridium is achieved by means of substoichiometric isotope dilution analysis, based on 192 Ir. The linear range is 1-11 nmol of iridium. (Auth.)

Separation of uranium and plutonium isotopes for measurement by multi collector inductively coupled plasma mass spectroscopy

International Nuclear Information System (INIS)

Martinelli, R.E.; Hamilton, T.F.; Kehl, S.R.; Williams, R.W.

2009-01-01

Uranium (U) and plutonium (Pu) isotopes in coral soils, contaminated by nuclear weapons testing in the northern Marshall Islands, were isolated by ion-exchange chromatography and analyzed by mass spectrometry. The soil samples were spiked with 233 U and 242 Pu tracers, dissolved in minerals acids, and U and Pu isotopes isolated and purified on commercially available ion-exchange columns. The ion-exchange technique employed a TEVA R column coupled to a UTEVA R column. U and Pu isotope fractions were then further isolated using separate elution schemes, and the purified fractions containing U and Pu isotopes analyzed sequentially using multi-collector inductively coupled plasma mass spectrometer (MCICP-MS). High precision measurements of 234 U/ 235 U, 238 U/ 235 U, 236 U/ 235 U, and 240 Pu/ 239 Pu in soil samples were attained using the described methodology and instrumentation, and provide a basis for conducting more detailed assessments of the behavior and transfer of uranium and plutonium in the environment. (author)

Determination of rare earth elements by liquid chromatographic separation using inductively coupled plasma mass spectrometric detection

International Nuclear Information System (INIS)

Braverman, D.S.

1992-01-01

High-performance liquid chromatography (HPLC) is used to separate the rare earth elements (REEs) prior to detection by inductively coupled plasma mass spectrometry (ICP-MS). The use of HPLC-ICP-MS in series combines the separation power and speed of HPLC with the sensitivity, isotopic selectivity and speed of ICP-MS. The detection limits for the REEs are in the sub-ng ml -1 range and the response is linear over four orders of magnitude. A preliminary comparison of isotope dilution and external standard results for the determination of REEs in National Institute of Standards and Technology (NIST) Standard Reference Material (SRM 1633a) Fly Ash is presented. (author)

Quantification of the 2-deoxyribonolactone and nucleoside 5'-aldehyde products of 2-deoxyribose oxidation in DNA and cells by isotope-dilution gas chromatography mass spectrometry: differential effects of gamma-radiation and Fe2+-EDTA.

Science.gov (United States)

Chan, Wan; Chen, Bingzi; Wang, Lianrong; Taghizadeh, Koli; Demott, Michael S; Dedon, Peter C

2010-05-05

The oxidation of 2-deoxyribose in DNA has emerged as a critical determinant of the cellular toxicity of oxidative damage to DNA, with oxidation of each carbon producing a unique spectrum of electrophilic products. We have developed and validated an isotope-dilution gas chromatography-coupled mass spectrometry (GC-MS) method for the rigorous quantification of two major 2-deoxyribose oxidation products: the 2-deoxyribonolactone abasic site of 1'-oxidation and the nucleoside 5'-aldehyde of 5'-oxidation chemistry. The method entails elimination of these products as 5-methylene-2(5H)-furanone (5MF) and furfural, respectively, followed by derivatization with pentafluorophenylhydrazine (PFPH), addition of isotopically labeled PFPH derivatives as internal standards, extraction of the derivatives, and quantification by GC-MS analysis. The precision and accuracy of the method were validated with oligodeoxynucleotides containing the 2-deoxyribonolactone and nucleoside 5'-aldehyde lesions. Further, the well-defined 2-deoxyribose oxidation chemistry of the enediyne antibiotics, neocarzinostatin and calicheamicin gamma(1)(I), was exploited in control studies, with neocarzinostatin producing 10 2-deoxyribonolactone and 300 nucleoside 5'-aldehyde per 10(6) nt per microM in accord with its established minor 1'- and major 5'-oxidation chemistry. Calicheamicin unexpectedly caused 1'-oxidation at a low level of 10 2-deoxyribonolactone per 10(6) nt per microM in addition to the expected predominance of 5'-oxidation at 560 nucleoside 5'-aldehyde per 10(6) nt per microM. The two hydroxyl radical-mediated DNA oxidants, gamma-radiation and Fe(2+)-EDTA, produced nucleoside 5'-aldehyde at a frequency of 57 per 10(6) nt per Gy (G-value 74 nmol/J) and 3.5 per 10(6) nt per microM, respectively, which amounted to 40% and 35%, respectively, of total 2-deoxyribose oxidation as measured by a plasmid nicking assay. However, gamma-radiation and Fe(2+)-EDTA produced different proportions of 2

Nicotine, acetanilide and urea multi-level2H-,13C- and15N-abundance reference materials for continuous-flow isotope ratio mass spectrometry

Science.gov (United States)

Schimmelmann, A.; Albertino, A.; Sauer, P.E.; Qi, H.; Molinie, R.; Mesnard, F.

2009-01-01

Accurate determinations of stable isotope ratios require a calibration using at least two reference materials with different isotopic compositions to anchor the isotopic scale and compensate for differences in machine slope. Ideally, the S values of these reference materials should bracket the isotopic range of samples with unknown S values. While the practice of analyzing two isotopically distinct reference materials is common for water (VSMOW-SLAP) and carbonates (NBS 19 and L-SVEC), the lack of widely available organic reference materials with distinct isotopic composition has hindered the practice when analyzing organic materials by elemental analysis/isotope ratio mass spectrometry (EA-IRMS). At present only L-glutamic acids USGS40 and USGS41 satisfy these requirements for ??13C and ??13N, with the limitation that L-glutamic acid is not suitable for analysis by gas chromatography (GC). We describe the development and quality testing of (i) four nicotine laboratory reference materials for on-line (i.e. continuous flow) hydrogen reductive gas chromatography-isotope ratio mass-spectrometry (GC-IRMS), (ii) five nicotines for oxidative C, N gas chromatography-combustion-isotope ratio mass-spectrometry (GC-C-IRMS, or GC-IRMS), and (iii) also three acetanilide and three urea reference materials for on-line oxidative EA-IRMS for C and N. Isotopic off-line calibration against international stable isotope measurement standards at Indiana University adhered to the 'principle of identical treatment'. The new reference materials cover the following isotopic ranges: ??2Hnicotine -162 to -45%o, ??13Cnicotine -30.05 to +7.72%, ?? 15Nnicotine -6.03 to +33.62%; ??15N acetanilide +1-18 to +40.57%; ??13Curea -34.13 to +11.71%, ??15Nurea +0.26 to +40.61% (recommended ?? values refer to calibration with NBS 19, L-SVEC, IAEA-N-1, and IAEA-N-2). Nicotines fill a gap as the first organic nitrogen stable isotope reference materials for GC-IRMS that are available with different ??13N

Performance and optimization of a combustion interface for isotope ratio monitoring gas chromatography/mass spectrometry

Science.gov (United States)

Merritt, D. A.; Freeman, K. H.; Ricci, M. P.; Studley, S. A.; Hayes, J. M.

1995-01-01

Conditions and systems for on-line combustion of effluents from capillary gas chromatographic columns and for removal of water vapor from product streams were tested. Organic carbon in gas chromatographic peaks 15 s wide and containing up to 30 nanomoles of carbon was quantitatively converted to CO2 by tubular combustion reactors, 200 x 0.5 mm, packed with CuO or NiO. No auxiliary source of O2 was required because oxygen was supplied by metal oxides. Spontaneous degradation of CuO limited the life of CuO reactors at T > 850 degrees C. Since NiO does not spontaneously degrade, its use might be favored, but Ni-bound carbon phases form and lead to inaccurate isotopic results at T Water must be removed from the gas stream transmitted to the mass spectrometer or else protonation of CO2 will lead to inaccuracy in isotopic analyses. Although thresholds for this effect vary between mass spectrometers, differential permeation of H2O through Nafion tubing was effective in both cases tested, but the required length of the Nafion membrane was 4 times greater for the more sensitive mass spectrometer.

Redox substoichiometric isotope dilution analysis of metallic arsenic for antimony

International Nuclear Information System (INIS)

Kambara, Tomihisa; Yoshioka, Hiroe; Suzuki, Junsuke; Shibata, Yasue.

1979-01-01

In 1 M HCl solution Sb(III) reacts with N-benzoyl-N-phenylhydroxylamine (BPHA) to form a complex extractable into chloroform while the extraction of Sb(V) is negligible. The redox substoichiometric isotope dilution analysis based on this reaction was applied to the determination of antimony in metallic arsenic. After the dissolution of metallic arsenic, Sb(V) was separated from As(V) by a tribenzylamine extraction from 8 M HCl solution and the extracted Sb(V) was stripped into 0.5 M NaOH solution. Thereafter, all the Sb(V) were completely reduced to Sb(III) by bubbling SO 2 gas through 3 M HCl solution. As the substoichiometric reaction, the oxidation of Sb(III) to Sb(V) by a substoichiometric amount of potassium dichromate was used, followed by separation of these species by the BPHA extraction of Sb(III). The substoichiometric oxidation of Sb(III) was found to be quantitative over HCl concentration range from 0.8 to 1.2 M. The amount of antimony was determined by isotope dilution analysis using the method of carrier amount variation. By the present method the determination of as small as 0.36 μg antimony was accomplished with a good accuracy (relative error; 5.6%) and also the method was successfully applied to the determination of antimony in arsenic samples containing known amounts of Sb(III) and in metallic arsenic. The present method gives reliable results with the good accuracy and precision. (author)

Sensitive determination of thiols in wine samples by a stable isotope-coded derivatization reagent d0/d4-acridone-10-ethyl-N-maleimide coupled with high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry analysis.

Science.gov (United States)

Lv, Zhengxian; You, Jinmao; Lu, Shuaimin; Sun, Weidi; Ji, Zhongyin; Sun, Zhiwei; Song, Cuihua; Chen, Guang; Li, Guoliang; Hu, Na; Zhou, Wu; Suo, Yourui

2017-03-31

As the key aroma compounds, varietal thiols are the crucial odorants responsible for the flavor of wines. Quantitative analysis of thiols can provide crucial information for the aroma profiles of different wine styles. In this study, a rapid and sensitive method for the simultaneous determination of six thiols in wine using d 0 /d 4 -acridone-10-ethyl-N-maleimide (d 0 /d 4 -AENM) as stable isotope-coded derivatization reagent (SICD) by high performance liquid chromatography-electrospray ionization-tandem mass spectrometry (HPLC-ESI-MS/MS) has been developed. Quantification of thiols was performed by using d 4 -AENM labeled thiols as the internal standards (IS), followed by stable isotope dilution HPLC-ESI-MS/MS analysis. The AENM derivatization combined with multiple reactions monitoring (MRM) not only allowed trace analysis of thiols due to the extremely high sensitivity, but also efficiently corrected the matrix effects during HPLC-MS/MS and the fluctuation in MS/MS signal intensity due to instrument. The obtained internal standard calibration curves for six thiols were linear over the range of 25-10,000pmol/L (R 2 ≥0.9961). Detection limits (LODs) for most of analytes were below 6.3pmol/L. The proposed method was successfully applied for the simultaneous determination of six kinds of thiols in wine samples with precisions ≤3.5% and recoveries ≥78.1%. In conclusion, the developed method is expected to be a promising tool for detection of trace thiols in wine and also in other complex matrix. Copyright © 2017 Elsevier B.V. All rights reserved.

The Influence of Seed-borne N in 15N Isotope Dilution Studies with Legumes The Influence of Seed-borne N in 15N Isotope Dilution Studies with Legumes

DEFF Research Database (Denmark)

Jensen, Erik Steen; Andersen, A. J.; Thomsen, J. D.

1985-01-01

The distriution of seed-borne N in shoot and root of pea and field bean was studied using three methods: 1) determination of the N content in shoot and root of plants grown in sand culture without other N sources. 2) 15N isotope dilution in plants grown in Rhizobium-free medium supplied with 15N-...... of corrections for seed-borne N in studies of nitrogen fixation in legumes is discussed....

On the interference of Kr during carbon isotope analysis of methane using continuous-flow combustion–isotope ratio mass spectrometry

Directory of Open Access Journals (Sweden)

J. Schmitt

2013-05-01

Full Text Available Stable carbon isotope analysis of methane (δ13C of CH4 on atmospheric samples is one key method to constrain the current and past atmospheric CH4 budget. A frequently applied measurement technique is gas chromatography (GC isotope ratio mass spectrometry (IRMS coupled to a combustion-preconcentration unit. This report shows that the atmospheric trace gas krypton (Kr can severely interfere during the mass spectrometric measurement, leading to significant biases in δ13C of CH4, if krypton is not sufficiently separated during the analysis. According to our experiments, the krypton interference is likely composed of two individual effects, with the lateral tailing of the doubly charged 86Kr peak affecting the neighbouring m/z 44 and partially the m/z 45 Faraday cups. Additionally, a broad signal affecting m/z 45 and especially m/z 46 is assumed to result from scattered ions of singly charged krypton. The introduced bias in the measured isotope ratios is dependent on the chromatographic separation, the krypton-to-CH4 mixing ratio in the sample, the focusing of the mass spectrometer as well as the detector configuration and can amount to up to several per mil in δ13C. Apart from technical solutions to avoid this interference, we present correction routines to a posteriori remove the bias.

Profiles of Steroid Hormones in Canine X-Linked Muscular Dystrophy via Stable Isotope Dilution LC-MS/MS.

Directory of Open Access Journals (Sweden)

Helio A Martins-Júnior

Full Text Available Golden retriever muscular dystrophy (GRMD provides the best animal model for characterizing the disease progress of the human disorder, Duchenne muscular dystrophy (DMD. The purpose of this study was to determine steroid hormone concentration profiles in healthy golden retriever dogs (control group - CtGR versus GRMD-gene carrier (CaGR and affected female dogs (AfCR. Therefore, a sensitive and specific analytical method was developed and validated to determine the estradiol, progesterone, cortisol, and testosterone levels in the canine serum by isotope dilution liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS. To more accurately understand the dynamic nature of the serum steroid profile, the fluctuating levels of these four steroid hormones over the estrous cycle were compared across the three experimental groups using a multivariate statistical analysis. The concentration profiles of estradiol, cortisol, progesterone, and testosterone revealed a characteristic pattern for each studied group at each specific estrous phase. Additionally, several important changes in the serum concentrations of cortisol and estradiol in the CaGR and AfCR groups seem to be correlated with the status and progression of the muscular dystrophy. A comprehensive and quantitative monitoring of steroid profiles throughout the estrous cycle of normal and GRMD dogs were achieved. Significant differences in these profiles were observed between GRMD and healthy animals, most notably for estradiol. These findings contribute to a better understanding of both dog reproduction and the muscular dystrophy pathology. Our data open new venues for hormonal behavior studies in dystrophinopathies and that may affect the quality of life of DMD patients.

Frontal and band displacement chromatography of the hydrogen isotopes on palladium; Chromatographies frontale et de deplacement de bande des isotopes de l'hydrogene sur palladium

Energy Technology Data Exchange (ETDEWEB)

Botter, F.; Menes, J.; Tistchenko, S.; Dirian, G. [Commissariat a l' Energie Atomique, Saclay (France). Centre d' Etudes Nucleaires

1964-07-01

As a result of hydrogen isotope separations which we have carried out on supports containing palladium, we believe that we can now make a double contribution, theoretical and experimental, to the work which has already been published in this field. From the fundamental point of view we have developed and studied the validity of a simple model, in our particular case of a separation coefficient {alpha} which is very different to unity. This model, which is of a counter-current isotopic exchange, neglects the longitudinal diffusion in the gas phase and the lateral diffusion in the adsorbed phase and only takes into account the surface resistance to exchange between the phases. It is therefore possible to estimate the efficiency of a chromatography column in terms of the height equivalent of a theoretical plate (HETP). The slight differences observed between the actual chromatograms and the simple model justify both the research undertaken into a more complex model taking into account the diffusion, and the adoption of a simple model for comparing the efficiency of several columns. We describe also a new and simple graphical method for deducing the number of theoretical plates of a column in chromatograms of the frontal and band displacement types. Experimentally we give in particular the criteria for the validity of the model used, the law as a function of the {sup {alpha}}H{sub 2}-HD temperature, the study of the HETP as a function of the various parameters on several palladium containing supports, and the possibilities of an application to preparative chromatography. (authors) [French] Grace aux separations des isotopes de l'hydrogene que nous avons realisees sur masses palladiees, nous pensons apporter aux etudes precedemment publiees dans ce domaine, une double contribution, theorique et experimentale. Du point de vue fondamental, on a developpe et etudie la validite d'un modele simple, dans notre cas particulier d'un coefficient de separation

High-precision ²⁷Al/²⁴Mg ratio determination using a modified isotope-dilution approach

DEFF Research Database (Denmark)

Paton, Chad; Schiller, Martin; Ulfbeck, David Garf

2012-01-01

saves time and minimises the risk of contamination of other samples with spike (which is added immediately prior to analysis). Repeat measurements of the BHVO-2, BCR-2, and BIR-1 international rock standards, as well as a gravimetrically prepared Al–Mg reference solution, indicate that our method......The precision of the 26Al–26Mg system—one of the most widely used chronometers for constraining the relative timing of events in the early solar system—is presently limited by methods for the determination of 27Al/24Mg ratios, which have seen little improvement in the last decade. We present...... a novel method for the measurement of 27Al/24Mg ratios in unpurified sample solutions by multiple-collector inductively coupled plasma mass spectrometry. Because Al is monoisotopic we use a modified isotope dilution approach that employs a mixed spike containing isotopically enriched 25Mg and natural 27Al...

Determination of thyroid hormones in mouse tissues by isotope-dilution microflow liquid chromatography-mass spectrometry method

DEFF Research Database (Denmark)

De Angelis, Meri; Giesert, Florian; Finan, Brian

2016-01-01

). The nano-UPLC system was interfaced with a quadrupole time-of-flight mass spectrometer (Q-TOF2-MS) using the positive ion mode electrospray ionization. In our analytical method the instrumental calibration curves were constructed from 0 to 100pgμL(-1) and all of them showed good linearity (r(2)>0.99...

Activity coefficients at infinite dilution for solutes in the trioctylmethylammonium bis(trifluoromethylsulfonyl)imide ionic liquid using gas-liquid chromatography

International Nuclear Information System (INIS)

Gwala, Nobuhle V.; Deenadayalu, Nirmala; Tumba, Kaniki; Ramjugernath, Deresh

2010-01-01

The activity coefficient at infinite dilution (γ 13 ∞ ) for 30 solutes: alkanes, alkenes, cycloalkanes, alkynes, ketones, alcohols, and aromatic compounds was determined from gas-liquid chromatography (glc) measurements at three temperatures (303.15, 313.15, and 323.15) K. The ionic liquid: trioctylmethylammonium bis(trifluoromethylsulfonyl)imide, was used as the stationary phase. For each temperature, γ 13 ∞ values were determined using two columns with different mass percent packing of the ionic liquid. The selectivity (S 12 ∞ ) value was calculated from the γ 13 ∞ to determine the suitability of the solvent as a potential entrainer for extractive distillation in the separation of an hexane/benzene mixture, indicative of a typical industrial separation problem for benchmarking purposes.

Comparison of isotope dilution and excretion methods for determining the half-life of ascorbic acid in the guinea pig

International Nuclear Information System (INIS)

Kipp, D.E.; Rivers, J.M.

1984-01-01

The half-life of ascorbic acid (AA) in guinea pigs was investigated by the isotope dilution and excretion methods. The dilution method measures [1-14C]AA disappearance from the plasma, whereas the excretion method measures the elimination of [1-14C]AA and the metabolites from the body. Two groups of animals underwent both isotope studies in reverse order. Animals were conditioned to the experimental procedures and fed 2.5 mg AA/100 g body weight orally to maintain a daily intake of the vitamin independent of food consumption. The two isotope procedures imposed similar stress on the animals, as determined by plasma cortisol levels and body weight changes. The AA half-life calculations of the rapidly exchangeable pool by the isotope dilution method yielded values of 1.23 and 0.34 hours for the two groups, respectively. The half-life of the slowly exchangeable pool for the two groups was 60.2 and 65.8 hours, respectively. The half-life of AA in the rapidly exchangeable pool, as measured by the excretion studies, was 4.57-8.75 hours. For the slowly exchangeable pool, it was 146-149 hours. The longer half-life of both pools obtained with the excretion method indicates that the isotope is disappearing from the plasma more rapidly than it is being excreted. This suggests that a portion of the [1-14C]AA leaving the plasma is removed to a body pool that is not sampled by the isotope excretion method

Improved analytical procedure for the determination of 210Pb and 210Po using alpha-spectrometric isotope dilution

International Nuclear Information System (INIS)

Urnezis, P.W.; Holtzman, R.B.

1981-01-01

An isotope dilution method has been incorporated into the 210 Pb- 210 Po analysis. A known amount of 209 Po is added to the sample before analysis. Then both 209 Po and 210 Po are deposited on a silver planchet which is assayed in an alpha spectrometer to determine the activities of each isotope. The recoveries generally range from 70% to 90%

Standard test method for analysis of isotopic composition of uranium in nuclear-grade fuel material by quadrupole inductively coupled plasma-mass spectrometry

CERN Document Server

American Society for Testing and Materials. Philadelphia

2000-01-01

1.1 This test method is applicable to the determination of the isotopic composition of uranium (U) in nuclear-grade fuel material. The following isotopic weight percentages are determined using a quadrupole inductively coupled plasma-mass spectrometer (Q-ICP-MS): 233U, 234U, 235U, 236U, and 238U. The analysis can be performed on various material matrices after acid dissolution and sample dilution into water or dilute nitric (HNO3) acid. These materials include: fuel product, uranium oxide, uranium oxide alloys, uranyl nitrate (UNH) crystals, and solutions. The sample preparation discussed in this test method focuses on fuel product material but may be used for uranium oxide or a uranium oxide alloy. Other preparation techniques may be used and some references are given. Purification of the uranium by anion-exchange extraction is not required for this test method, as it is required by other test methods such as radiochemistry and thermal ionization mass spectroscopy (TIMS). This test method is also described i...

Formation of trihalomethanes from the halogenation of 1,3-dihydroxybenzenes in dilute aqueous solution: synthesis of 2-13C-resorcinol and its reaction with chlorine and bromine

International Nuclear Information System (INIS)

Boyce, S.D.; Barefoot, A.C.; Britton, D.R.; Hornig, J.F.

1983-01-01

As part of this study, the reaction of bromine with resorcinol and structurally related substrates to produce bromoform was examined. Preliminary results suggest that the chlorination and bromination of dihydroxybenzenes proceeded by similar reaction pathways. This chapter describes the successful synthesis of 2- 13 C-1, 3-dihydroxybenzene. Treatment of the isotopically labelled substrate with chlorine and bromine in dilute aqueous solution has elucidated many important details of the sequence of reactions leading to the production of chloroform (CHCl 3 ) and bromoform (CHBr 3 ). The 13 C-enriched products and intermediates formed during these reactions were identified by gas chromatography/mass spectrometry

Application of double-spike isotope dilution for the accurate determination of Cr(III), Cr(VI) and total Cr in yeast.

Science.gov (United States)

Yang, Lu; Ciceri, Elena; Mester, Zoltán; Sturgeon, Ralph E

2006-11-01

A method is presented for the simultaneous determination of Cr(III) and Cr(VI) in yeast using species-specific double-spike isotope dilution (SSDSID) with anion-exchange liquid chromatography (LC) separation and sector field inductively coupled plasma mass spectrometric (SF-ICP-MS) detection. Total Cr is quantitated using ID SF-ICP-MS. Samples were digested on a hot plate at 95+/-2 degrees C for 6 h in an alkaline solution of 0.5 M NaOH and 0.28 M Na2CO3 for the determination of Cr(III) and Cr(VI), whereas microwave-assisted decomposition with HNO3 and H2O2 was used for the determination of total Cr. Concentrations of 2,014+/-16, 1,952+/-103 and 76+/-48 mg kg-1 (one standard deviation, n=4, 3, 3), respectively were obtained for total Cr, Cr(III) and Cr(VI) in the yeast sample. Significant oxidation of Cr(III) to Cr(VI) (24.2+/-7.6% Cr(III) oxidized, n=3) and reduction of Cr(VI) to Cr(III) (37.6+/-6.5% Cr(VI) reduced, n=3) occurred during alkaline extraction and subsequent chromatographic separation at pH 7. Despite this significant bidirectional redox transformation, quantitative recoveries for both Cr(III) and Cr(VI) were achieved using the SSDSID method. In addition, mass balance between total Cr and the sum of Cr(III) and Cr(VI) concentrations was achieved. Method detection limits of 0.3, 2 and 30 mg kg-1 were obtained for total Cr, Cr(VI) and Cr(III), respectively, based on a 0.2-g sub-sample.

Basic methods of isotope analysis

International Nuclear Information System (INIS)

Ochkin, A.V.; Rozenkevich, M.B.

2000-01-01

The bases of the most applied methods of the isotope analysis are briefly presented. The possibilities and analytical characteristics of the mass-spectrometric, spectral, radiochemical and special methods of the isotope analysis, including application of the magnetic resonance, chromatography and refractometry, are considered [ru

Determination of inositol 1,4,5-trisphosphate levels in Dictyostelium by isotope dilution assay

International Nuclear Information System (INIS)

Van Haastert, P.J.

1989-01-01

A commercial isotope dilution assay was used for the determination of Ins(1,4,5)P3 levels in the microorganism Dictyostelium discoideum. Cross-reactivity in the assay was detected with extracts from cells and the medium. The compound which induced this cross-reactivity was tentatively identified as Ins(1,4,5)P3 by (i) codegradation with authentic [ 32 P]Ins(1,4,5)P3 by three specific Ins(1,4,5)P3 phosphatases, and (ii) co-chromatography with authentic [ 32 P]Ins(1,4,5)P3 on HPLC columns. The cellular concentration was estimated as 165 +/- 42 pmol/10(8) cells, yielding a mean intracellular Ins(1,4,5)P3 concentration of 3.3 microM. Dictyostelium cells secrete large amounts of Ins(1,4,5)P3 at a rate of about 10% of the cellular content per minute, yielding about 0.13 microM extracellular Ins(1,4,5)P3 after 15 min in a suspension of 10(8) cells/ml. The chemoattractant cAMP induced a transient increase of the Ins(1,4,5)P3 concentration; the data suggest an intracacellular rise from 3.3 to 5.5 microM with a maximum at 6 s after stimulation

Nicotine, acetanilide and urea multi-level 2H-, 13C- and 15N-abundance reference materials for continuous-flow isotope ratio mass spectrometry.

Science.gov (United States)

Schimmelmann, Arndt; Albertino, Andrea; Sauer, Peter E; Qi, Haiping; Molinie, Roland; Mesnard, François

2009-11-01

Accurate determinations of stable isotope ratios require a calibration using at least two reference materials with different isotopic compositions to anchor the isotopic scale and compensate for differences in machine slope. Ideally, the delta values of these reference materials should bracket the isotopic range of samples with unknown delta values. While the practice of analyzing two isotopically distinct reference materials is common for water (VSMOW-SLAP) and carbonates (NBS 19 and L-SVEC), the lack of widely available organic reference materials with distinct isotopic composition has hindered the practice when analyzing organic materials by elemental analysis/isotope ratio mass spectrometry (EA-IRMS). At present only L-glutamic acids USGS40 and USGS41 satisfy these requirements for delta13C and delta15N, with the limitation that L-glutamic acid is not suitable for analysis by gas chromatography (GC). We describe the development and quality testing of (i) four nicotine laboratory reference materials for on-line (i.e. continuous flow) hydrogen reductive gas chromatography-isotope ratio mass-spectrometry (GC-IRMS), (ii) five nicotines for oxidative C, N gas chromatography-combustion-isotope ratio mass-spectrometry (GC-C-IRMS, or GC-IRMS), and (iii) also three acetanilide and three urea reference materials for on-line oxidative EA-IRMS for C and N. Isotopic off-line calibration against international stable isotope measurement standards at Indiana University adhered to the 'principle of identical treatment'. The new reference materials cover the following isotopic ranges: delta2H(nicotine) -162 to -45 per thousand, delta13C(nicotine) -30.05 to +7.72 per thousand, delta15N(nicotine) -6.03 to +33.62 per thousand; delta15N(acetanilide) +1.18 to +40.57 per thousand; delta13C(urea) -34.13 to +11.71 per thousand, delta15N(urea) +0.26 to +40.61 per thousand (recommended delta values refer to calibration with NBS 19, L-SVEC, IAEA-N-1, and IAEA-N-2). Nicotines fill a gap as

Multi-column chromatography and the use of isotopes in the study of steroid metabolism

International Nuclear Information System (INIS)

Sayegh, J.F.; Vestergaard, P.

1978-01-01

Multi-column liquid chromatography is demonstrated to be a technique well suited for isotope experiments involving administration of labelled cortisol. It has potential for secretion rate determinations, for dynamic studies of cortisol metabolism and for work with stable isotopes. (author)

Trace uranium analysis in geological sample by isotope dilution-alpha spectrometry and comparison with other techniques

International Nuclear Information System (INIS)

Shihomatsu, H.M.; Iyer, S.S.

1988-12-01

Establishment of uranium determination in geological samples by alpha spectrometric isotope dilution technique using 233 U tracer is described in the present work. The various steps involved in the method namely, preparation of the sample, electrodeposition, alpha spectrometry, isotope dilution, calculation of the concentration and error statistics are discussed in detail. The experimental parameters for the electrodeposition of uranium, like current density, pH concentration of the electrolyte solution, deposition time, electrode distance were all optimised based on the efficiency of the deposition. The total accuracy and precision of the IDAS using 233 U tracer in the determination of uranium in mineral and granite samples were of the order of 1 to 2% for the concentration range of 50-1500 ppm of U. Our results are compared with those obtained by others workers using similar and different techniques. (author) [pt

Automatic processing of isotopic dilution curves obtained by precordial detection

International Nuclear Information System (INIS)

Verite, J.C.

1973-01-01

Dilution curves pose two distinct problems: that of their acquisition and that of their processing. A study devoted to the latter aspect only was presented. It was necessary to satisfy two important conditions: the treatment procedure, although applied to a single category of curves (isotopic dilution curves obtained by precordial detection), had to be as general as possible; to allow dissemination of the method the equipment used had to be relatively modest and inexpensive. A simple method, considering the curve processing as a process identification, was developed and should enable the mean heart cavity volume and certain pulmonary circulation parameters to be determined. Considerable difficulties were encountered, limiting the value of the results obtained though not condemning the method itself. The curve processing question raised the problem of their acquisition, i.e. the number of these curves and their meaning. A list of the difficulties encountered is followed by a set of possible solutions, a solution being understood to mean a curve processing combination where the overlapping between the two aspects of the problem is accounted for [fr

Precision Mass Measurement of Argon Isotopes

CERN Multimedia

Lunney, D

2002-01-01

% IS388\\\\ \\\\ A precision mass measurement of the neutron-deficient isotopes $^{32,33,34}$Ar is proposed. Mass values of these isotopes are of importance for: a) a stringent test of the Isobaric-Multiplet- Mass-Equation, b) a verification of the correctness of calculated charge-dependent corrections as used in super-allowed $\\beta$- decay studies aiming at a test of the CVC hypothesis, and c) the determination of the kinematics in electron-neutrino correlation experiments searching for scalar currents in weak interaction. The measurements will be carried out with the ISOLTRAP Penning trap mass spectrometer.

Measurement of O(6)-alkylguanine-DNA alkyltransferase activity in tumour cells using stable isotope dilution HPLC-ESI-MS/MS.

Science.gov (United States)

Sun, Guohui; Zhao, Lijiao; Fan, Tengjiao; Ren, Ting; Zhong, Rugang

2016-10-15

The repair of DNA mediated by O(6)-alkylguanine-DNA alkyltransferase (AGT) provides protection against DNA damage from endogenous or exogenous alkylation of the O(6) position of guanine. However, this repair acts as a double-edged sword in cancer treatment, as it not only protects normal cells from chemotherapy-associated toxicities, but also results in cancer cell resistance to guanine O(6)-alkylating antitumour agents. Thus, AGT plays an important role in predicting the individual susceptibility to guanine O(6)-alkylating carcinogens and chemotherapies. Accordingly, it is necessary to establish a quantitative method for determining AGT activity with high accuracy, sensitivity and practicality. Here, we describe a novel nonradioactive method for measuring AGT activity using stable isotope dilution high-performance liquid chromatography electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS). This method is based on the irreversibility of the removal of the O(6)-alkyl group from guanine by AGT and on the high affinity of O(6)-benzylguanine (O(6)-BG) as an AGT substrate. HPLC-ESI-MS/MS was used to measure the AGT activities in cell protein extracts from eight tumour lines, demonstrating that AGT activity was quite variable among different cell lines, ranging from nondetectable to 1021 fmol/mg protein. The experiments performed in intact tumour cells yielded similar results but exhibited slightly higher activities than those observed in cell protein extracts. The accuracy of this method was confirmed by an examination of AGT expression levels using western blotting analysis. To our knowledge, this method is the first mass spectrometry-based AGT activity assay, and will likely provide assistance in the screening of cancer risk or the application of chemotherapies. Copyright © 2016 Elsevier B.V. All rights reserved.

Recent applications of gas chromatography with high-resolution mass spectrometry.

Science.gov (United States)

Špánik, Ivan; Machyňáková, Andrea

2018-01-01

Gas chromatography coupled to high-resolution mass spectrometry is a powerful analytical method that combines excellent separation power of gas chromatography with improved identification based on an accurate mass measurement. These features designate gas chromatography with high-resolution mass spectrometry as the first choice for identification and structure elucidation of unknown volatile and semi-volatile organic compounds. Gas chromatography with high-resolution mass spectrometry quantitative analyses was previously focused on the determination of dioxins and related compounds using magnetic sector type analyzers, a standing requirement of many international standards. The introduction of a quadrupole high-resolution time-of-flight mass analyzer broadened interest in this method and novel applications were developed, especially for multi-target screening purposes. This review is focused on the development and the most interesting applications of gas chromatography coupled to high-resolution mass spectrometry towards analysis of environmental matrices, biological fluids, and food safety since 2010. The main attention is paid to various approaches and applications of gas chromatography coupled to high-resolution mass spectrometry for non-target screening to identify contaminants and to characterize the chemical composition of environmental, food, and biological samples. The most interesting quantitative applications, where a significant contribution of gas chromatography with high-resolution mass spectrometry over the currently used methods is expected, will be discussed as well. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.