EXPERIENCE OF ALPROSTADIL APPLICATION AGAINST RAYNAUD'S SYNDROME AMONG CHILDREN

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E.I. Alexeeva

2007-01-01

Full Text Available The article provides the data on the causes and mechanisms of Raynaud's syndrome development. initial or idiopathic Raynaud's syndrome is characterized by the spasm of the digital arteries and thermoregulatory vessels of skin under the impact of the cold without any signs of vessel lesions. In the event of secondary Raynaud's syndrome, there is combination of Raynaud's syndrome with the symptoms of other diseases. Secondary raynaud's syndrome is most often associated with scleroderma systematica, systemic erythema centrifugum, other rheumatic diseases, hematologic disc orders and intake of some medications. There is also data on the opportunity to apply the synthetic medication prostaglandin е 1 — alprostadil to treat Raynaud's syndrome associated with rheumatic diseases. The given clinical example demonstrates high efficacy of alprostadil in case of the patient, suffering from scleroderma systematica and generalized Raynaud's syndrome.Key words: children, scleroderma systematica, alprostadil, Raynaud's syndrome.

Clinical effect of alprostadil in patients with septic shock associated with acute respiratory distress syndrome

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Li-ping LIU

2017-10-01

Full Text Available Objective To evaluate the clinical efficacy of alprostadil in patients with septic shock associated with acute respiratory distress syndrome (ARDS, and to explore its possible mechanism. Methods From January 2015 to June 2016, patients with septic shock associated with ARDS and meeting the inclusion criteria were involved in the study in department of critical care medicine in First Hospital of Lanzhou University and randomly divided into the control group and alprostadil group. The standard treatment was given in control group, alprostadil 10μg 2/d was given in alprostadil group on base of standard treatment. Monitoring indexes were recorded in 1, 3 and 6 days after enrollment. General condition of patients, APACHE Ⅱ score, ventilator conditions (PO2, PCO2, RR, PEEP, FiO2, oxygenation index, airway resistance, lung compliance, mechanical ventilation time, ICU stay time, hospital follow-up, 28-day follow-up, immune index (CD4+/CD8+, inflammatory markers (CRP, PCT, IL-6 were monitored. Results Sixty-five patients were included in this study, 32 in control group and 33 in alprostadil group. At 3 and 6 days after the treatment, APACHE Ⅱ score, respiratory rate (RR, the inspired oxygen concentration (FiO2, airway resistance, and C reactive protein (CRP, procalcitonin (PCT -6 and interleukin (IL-6 levels significantly decreased, compared with pretreatment and 1 day posttreatment, in the two groups and lower in alprostadil group than in the control group on the 6th day (P<0.05; at the same time, these indexes such as arterial partial pressure of oxygen (PaO2, lung compliance, oxygenation index, CD4+/CD8+ significantly increased 3 and 6 days after the treatment compared with pretreatment and 1 day posttreatment in the two groups, and on the 6th day, significantly higher in the alprostadil group than in the control group (P<0.05. Time of mechanical ventilation, ICU stay and hospital stay in the alprostadil group was respectively lower than that in

Clinical observation of alprostadil combined with glucocorticoids on acute optic neuritis

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Ke-Shun Fan

2015-09-01

Full Text Available AIM: To study the clinical effect of alprostadil combined with glucocorticoids in the treatment of acute optic neuritis(AON.METHODS: Seventy patients(70 eyeswith AON from January, 2012 to June, 2014 were randomly divided into two groups. 35 patients in observation group were used 10ug alprostadil with 10mL normal saline(NSby intravenous injection, once/d for 7d/one treatment course, and 10mL NS was used by intravenous injection in 35 patients of control group. Besides, the two groups were treated with the combined therapy as follows: 20mg methylprednisolone was injected periglomerularly beside the eyeballs, once /3d for 3 times; 800～1 000mg of methylprednisolone through intravenous drip for 3d, once/d; after 3d, oral administration of prednisone acetate for 1wk, 1mg/(kg·d; after 1wk, the dose decreased to 5mg/wk until withdraw. Simultaneously, oral administration of ranitidine capsules, calcium carbonate and vitamin D3 tablets were combined in the supportive treament. The differences of curative effect between two groups were comparatively analyzed.RESULTS: In the observation group, 25 eyes(71.4%were markedly effective, 7 eyes(20.0%were valid and 3 eyes(8.6%were invalid, and the total effective rate was 91.4%. In the control group, 15 eyes(42.9%were markedly effective, 14 eyes(40.0%were valid and 6 eyes(17.1%were invalid, and the total effective rate was 82.9%. The difference of total effective rate between the two groups was not statistically significant(P=0.477, but there was a significant difference in markedly effective rate between the two groups(χ2=5.833, P=0.016.CONCLUSION: Alprostadil combined with glucocorticoids is effective for AON, and it is worth of advocation.

Effect of alprostadil combined with conventional therapy on serum markers in patients with acute cerebral infarction

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Li-Lan Chen

2016-01-01

Full Text Available Objective: To study the effect of alprostadil combined with conventional therapy on serum markers in patients with acute cerebral infarction. Methods: Patients with acute cerebral infarction treated in our hospital from May 2012 to August 2014 were enrolled and randomly divided into two groups. Observation group received alprostadil combined with conventional therapy and control group received conventional treatment. Then serum markers of both groups were compared. Results: (1 contents of serum nerve function related molecules: serum NSE and S100β contents of observation group showed a decreasing trend, and BDNF and NGF contents showed an increasing trend; (2 contents of atherosclerosis related enzymes: serum GGT, iNOS and MPO contents of observation group showed a decreasing trend, and PON1 and PON2 contents showed an increasing trend; (3 platelet activation related molecules: serum PPARγ, CD62p, YKL-40, sCD40L and Fibulin-5 contents of observation group all showed a decreasing trend. Conclusions: Alprostadil combined with conventional treatment is helpful to alleviate neuronal damage and inhibit the processes of atherosclerosis and platelet activation; it’s an ideal method for treating acute cerebral infarction.

Determination of the molecular complexation constant between alprostadil and alpha-cyclodextrin by conductometry: implications for a freeze-dried formulation.

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Sheehy, Philip M; Ramstad, Tore

2005-10-04

The binding constant between alprostadil (PGE1) and alpha-cyclodextrin (alpha-CD) was determined at four temperatures using conductance measurements. Alpha-cyclodextrin is an excipient material in Caverject dual chamber syringe (DCS) that was added to enhance stability. The binding constant was used to calculate the amount of PGE1 free upon reconstitution and injection, since only the free drug is clinically active. The conductivity measurement is based on a decrease in specific conductance as alprostadil is titrated with alpha-CD. The change in conductivity was plotted versus free ligand concentration (alpha-CD) to generate a binding curve. As the value of the binding constant proved to be dependent on substrate concentration, it is really a pseudo binding constant. A value of 742+/-60 M(-1) was obtained for a 0.5 mM solution of alprostadil at 27 degrees C and a value of 550+/-52 M(-1) at 37 degrees C. These results compare favorably to values previously obtained by NMR and capillary electrophoresis. Calculation of the fraction PGE1 free upon reconstitution and injection show it to approach the desired outcome of one. Hence, the amount of drug delivered by Caverject DCS is nominally equivalent to that delivered by Caverject S. Po., a predecessor product that contains no alpha-cyclodextrin.

Clinical effect of alprostadil combined with entecavir in treatment of HBV-related liver failure complicated by ascites

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JI Huichun

2016-11-01

Full Text Available ObjectiveTo investigate the clinical effect of alprostadil combined with entecavir in the treatment of HBV-related liver failure complicated by ascites. MethodsA total of 84 patients with HBV-related liver failure complicated by ascites who were hospitalized and treated in No. 97 Hospital of PLA from September 2011 to June 2014 were enrolled and randomly divided into treatment group (42 patients and control group (42 patients. The patients in both groups were given conventional treatment for liver protection, jaundice clearance, diuresis, and albumin nutritional support. The patients in the control group were given entecavir in addition, while those in the treatment group were given alprostadil combined with entecavir in addition. The liver function parameters ［total bilirubin (TBil, alanine aminotransferase (ALT, and aspartate aminotransferase (AST］, prothrombin activity (PTA, HBV DNA load, clinical outcome, 24-hour urine volume, and ascites regression before and after treatment were observed and recorded. The t-test was used for comparison of continuous data between groups, and the chi-square test was used for comparison of categorical data between groups. ResultsBoth groups had significant changes in the liver function parameters (TBil, ALT, and AST, PTA, and HBV DNA load after treatment (all P＜0.05. There were significant differences in TBil, ALT, AST, and PTA after treatment between the treatment group and the control group (TBil: 197.4±47.6 μmol/L vs 287.5±150.6 μmol/L, t=2.30, P＜0.05; ALT: 189.4±63.8 U/L vs 263.4±79.5 U/L, t=2.73, P＜0.05; AST: 138.7±87.5 U/L vs 250.8±90.4 U/L, t=3.43, P＜0.05; PTA: 63.5%±17.0% vs 45.5%±15.1%, t=2.60, P＜0.05. The treatment group had significantly higher marked response rate and overall response rate concerning clinical outcome than the control group (marked response rate: 40.48% vs 28.57%, χ2=4.32, P＜0.05; overall response rate: 85.71% vs 66.67%, χ2=4.20, P＜0.05. The treatment

Treatment of infertility in men with spinal cord injury

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Brackett, N.L.; Lynne, C.M.; El Dib, Hussein Ibrahim El Desouki Hussein

2010-01-01

Most men with spinal cord injury (SCI) are infertile. Erectile dysfunction, ejaculatory dysfunction and semen abnormalities contribute to the problem. Treatments for erectile dysfunction include phosphodiesterase type 5 inhibitors, intracavernous injections of alprostadil, penile prostheses...

Identification of Drugs that Regulate Dermal Stem Cells and Enhance Skin Repair

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Sibel Naska

2016-01-01

Full Text Available Here, we asked whether we could identify pharmacological agents that enhance endogenous stem cell function to promote skin repair, focusing on skin-derived precursors (SKPs, a dermal precursor cell population. Libraries of compounds already used in humans were screened for their ability to enhance the self-renewal of human and rodent SKPs. We identified and validated five such compounds, and showed that two of them, alprostadil and trimebutine maleate, enhanced the repair of full thickness skin wounds in middle-aged mice. Moreover, SKPs isolated from drug-treated skin displayed long-term increases in self-renewal when cultured in basal growth medium without drugs. Both alprostadil and trimebutine maleate likely mediated increases in SKP self-renewal by moderate hyperactivation of the MEK-ERK pathway. These findings identify candidates for potential clinical use in human skin repair, and provide support for the idea that pharmacological activation of endogenous tissue precursors represents a viable therapeutic strategy.

Pharmacotherapy of erectile dysfunction: Current standards

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Kew-Kim Chew

2006-01-01

Full Text Available Pharmacotherapy is currently the therapeutic option of choice for erectile dysfunction. Comprising mainly intracavernosal injection therapy using alprostadil or alprostadil combined with phentolamine and/or papaverine and oral phosphodiesterase-5 inhibitors, it is safe and effective if appropriately prescribed and administered. The medications in current use produce satisfactory erectile responses by enhancing cavernosal vasodilatation mainly through their ability to promote relaxation of the smooth muscle cells in the corpora cavernosa involving the synthesis and activity of nitric oxide via the cyclic guanosine monophosphate and cyclic adenosine monophosphate biochemical pathways. The main side-effects and complications of intracavernosal injections are postinjection pain, prolonged erections, priapism and penile fibrosis. There may be a variety of side-effects with phosphodiesterase-5 inhibition but these are usually inconsequential. Recent serious ill health and the need for ongoing long-acting nitrate therapy or frequent use of short-acting nitrates for angina are absolute contraindications to the use of phosphodiesterase-5 inhibitors. Caution has to be exercised in prescribing phosphodiesterase-5 inhibitors for patients with impaired renal or hepatic functions or receiving multi-drug therapy for any systemic disease. All patients presenting with erectile dysfunction should be investigated and treated for cardiovascular risk factors. They should also be counseled regarding lifestyle factors particularly healthy balanced diet, regular physical exercise and inappropriate social habits.

Treatment of infertility in men with spinal cord injury

DEFF Research Database (Denmark)

Brackett, N.L.; Lynne, C.M.; El Dib, Hussein Ibrahim El Desouki Hussein

2010-01-01

Most men with spinal cord injury (SCI) are infertile. Erectile dysfunction, ejaculatory dysfunction and semen abnormalities contribute to the problem. Treatments for erectile dysfunction include phosphodiesterase type 5 inhibitors, intracavernous injections of alprostadil, penile prostheses...... of intrauterine insemination increases as the total motile sperm count inseminated increases. In vitro fertilization and intracytoplasmic sperm injection are options in cases of extremely low total motile sperm count. Reproductive outcomes for SCI male factor infertility are similar to outcomes for general male...... factor infertility...

Pharmacologic Therapy in Men's Health: Hypogonadism, Erectile Dysfunction, and Benign Prostatic Hyperplasia.

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Berkseth, Kathryn E; Thirumalai, Arthi; Amory, John K

2016-07-01

This article reviews current pharmacologic treatment options for 3 common men's health concerns: hypogonadism, erectile dysfunction (ED), and benign prostatic hyperplasia (BPH). Specific topics addressed include: management of male hypogonadism using testosterone replacement therapy, use of oral phosphodiesterase inhibitors as first-line therapy for men with ED and the utility of intraurethral and intrapenile alprostadil injections for patients who do not respond to oral medications, and the role of alpha1-adrenergic antagonists, 5-alpha-reductase inhibitors, anticholinergic agents, and herbal therapies in the management of BPH. Copyright © 2016 Elsevier Inc. All rights reserved.

Bilateral external and internal pudendal veins embolization treatment for venogenic erectile dysfunction

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Daniel Lee, BBA, BS

2017-03-01

Full Text Available Erectile dysfunction (ED or impotence is estimated to affect around 20-30 million men in the United States (Rhoden et al, 2002. Vascular etiology is purported to be the most prevalent cause of ED in the elderly population, with venogenic ED being the most common subtype (Shafik et al, 2007; Rebonato et al, 2014. A patient, who developed severe venogenic ED, was referred to interventional radiology after ineffective pharmaceutical treatments. Selective embolization of bilateral external and internal pudendal veins was performed through accessing the deep dorsal vein of penis. Subsequent venogram verified successful embolization with stasis within the outflow of the deep dorsal vein of penis. Close to 6 weeks after the procedure, the patient purports to be able to achieve approximately 65% of full penile erection and complete penile erection with penile stimulation and 0.25 mL injection of alprostadil after 25 minutes.

Feline penile erection induced by topical glans penis application of combination alprostadil and SEPA (Topiglan).

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Usta, M F; Sanabria, J; Bivalacqua, T J; Hellstrom, W J G; Sanabriav, J

2004-02-01

The objective of this study was to evaluate the efficacy of topically applied prostaglandin E1 (PGE(1))+5% SEPA (soft enhancement of percutaneous absorption) on the glans penis in a feline erection model. Erectile response after glans penis administration of PGE(1)+5% SEPA cream (Topiglan, MacroChem Co., Lexington, MA, USA) was compared to the erectile response after intracavernosal administration of the triple-drug combination (1.65 mg papaverine, 25 microg phentolamine, and 0.5 microg PGE(1)). The placebo cream and increasing concentrations (0.25%, 2.5 mg/ml; 0.5%, 5 mg/ml; and 1%, 10 mg/ml) of PGE(1)+5% SEPA were applied in a total volume of 0.1 ml via a plastic needle-less syringe. The control triple-drug combination was administrated intracavernosally via a 30-gauge needle at the completion of each experiment to serve as a control reference. With each application of placebo, PGE(1)+SEPA, and the triple-drug combination, changes in intracavernosal pressure and systemic blood pressure were continuously monitored. Topical application of PGE(1)+SEPA induced increases in intracavernosal pressure in a dose-dependent manner, with minimal effects on systemic blood pressure. The increases obtained with 1% PGE(1) Topiglan cream were similar to the intracavernosal pressure values elicited by the standard intracavernosal triple-drug combination. These data demonstrate that topical glans penis application of PGE(1)+SEPA can induce an erectile response in cats with minimal systemic adverse effects. Oral pharmacological agents are the first-line treatment for male ED. Studies investigating the effectiveness of noninvasive modalities such as topical therapy should continue, because these agents have the potential to avoid the systemic effects commonly seen with oral therapies. Additionally, topical therapy may also benefit patients who are unresponsive to oral agents or have explicit contraindications. Topical PGE(1) application to the glans penis may become an important treatment option in selected patients suffering from erectile dysfunction.

Considerations on prevention of phlebitis and venous pain from intravenous prostaglandin E(1) administration by adjusting solution pH: in vitro manipulations affecting pH.

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Kohno, Emiko; Nishikata, Mayumi; Okamura, Noboru; Matsuyama, Kenji

2008-01-01

Prostaglandin E(1) (PGE(1); Alprostadil Alfadex) is a potent vasodilator and inhibitor of platelet aggregation used to treat patients with peripheral vascular disease. The main adverse effects of intravenous PGE(1) administration, phlebitis and venous pain, arise from the unphysiologically low pH of infusion solutions. When PGE(1) infusion solutions with a pH value greater then 6 are used, phlebitis and venous pain are considered to be avoidable. Beginning with a PGE(1) infusion solution with pH greater than 6, we add the amount of 7% sodium bicarbonate needed to bring the solution to pH 7.4 if phlebitis or venous pain develops. In the present study we established a convenient nomogram showing the relationship between the titratable acidity of various infusion solutions and the volume of 7% sodium bicarbonate required to attain pH 7.4 for preventing the phlebitis and venous pain associated with PGE(1) infusion.

TREATMENT OF ERECTILE DYSFUNCTION IN PATIENTS WITH PROSTATE TUMOR AFTER RADICAL PROSTATECTOMY

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A. V. Babintsev

2017-01-01

Full Text Available Prostate cancer (PC treatment is a pressing problem both inRussiaand worldwide. According to data for Saint-Petersburg, from 1990 to 2002 morbidity increase rate for PC was 141.3 %. Even after nerve-sparing radical prostatectomy (RP erectile dysfunction of some level is observed in 65–75 % of patients. During follow-up examination, data on sexual history were gathered including information on past and current sexual contacts. A questionnaire based on the International Index of Erectile Function was used which allows to evaluate different parameters of sexual function (sexual drive, erection, orgasm, ejaculation, sexual act, and satisfaction with sexual relationships, as well as determine treatment effectiveness. We performed combined two-stage treatment of erectile dysfunction in patients with PC after RP. At the first stage, phosphodiesterase type 5 inhibitors (sildenafil 100 mg were used. If the drug was ineffective, the second stage was initiated (intracavernosal alprostadil injections. Drug effectiveness, complications, patient compliancy were evaluated.

A standardized procedure for using human corpus cavernosum strips to evaluate drug activity.

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Mirone, V; Sorrentino, R; di Villa Bianca, R; Imbimbo, C; Palmieri, A; Fusco, F; Tajana, G; Cirino, G

2000-01-01

The main problem of using human corpus cavernosum (HCC) tissue to perform bioassay is linked to its limited availability further complicated by the heterogeneous source of the tissues used. Here, we show that gender reassignment is a reliable source of human tissue without major ethical problems. Indeed, the entire corpus cavernosum is obtained from the surgery procedure, which allows creating a standardized procedure to prepare HCC strip. In addition, human tissue, if kept in the fridge in the condition described, does not loose its ability to contract to phenylephrine (PE; alpha agonist), angiotensin II (AG II) and KCl up to 4 days. Furthermore, once contracted with PE, HCC relaxes to acetylcholine (endothelium-dependent mechanism); sodium nitroprusside (endothelium-independent mechanism); cromakalim (CRK), a K(ATP) channel opener; or alprostadil, a synthetic PGE2 (ALPR). In conclusion, we have standardized a procedure that allows the use of HCC strips to evaluate drug activity and/or to study pathophysiological mechanisms with an intact functional human tissue up to 4 days from the surgery procedure.

Tissue Hypoperfusion, Hypercoagulopathy, and Kidney and Liver Dysfunction after Ingestion of a Naphazoline-Containing Antiseptic

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Yuko Ono

2017-01-01

Full Text Available Naphazoline is a peripheral α2-adrenergic receptor agonist commonly used as a topical decongestant. In Japan, over-the-counter antiseptics often contain naphazoline to effect local hemostasis. We present the first case involving the development of hypercoagulopathy, with kidney and liver dysfunction, following a naphazoline overdose. A 22-year-old Japanese woman with a history of depression ingested 160 mL of a commercially available antiseptic containing 0.1% naphazoline. Three days later, she was brought to the emergency department because of general fatigue, nausea, and vomiting. Physical examination revealed cool, pale extremities. Laboratory data showed evidence of severe kidney and liver dysfunction (creatinine, 9.2 mg/dL; alanine aminotransferase, 2948 IU/L, hypercoagulation (D-dimers, 58.3 μg/mL, and thrombocytopenia (platelet count, 90,000/μL. After infusion of normal saline, intravenous administration of alprostadil, and hemodiafiltration, her organ function completely recovered. Because both the kidney and liver express α2-adrenergic receptors, their failure was likely associated with naphazoline overdose-induced hypoperfusion. The most plausible causes of hypercoagulation are peripheral low perfusion and subsequent microthrombus formation. This case illustrates that severe organ dysfunction can occur following over-the-counter antiseptic ingestion and serves as a caution for both drug manufacturers and healthcare professionals.

Case of Paecilomyces lilacinus infection occurring in necrotizing fasciitis-associated skin ulcers on the face and surrounding a tracheotomy stoma.

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Nagamoto, Eiko; Fujisawa, Akihiko; Yoshino, Yuichiro; Yoshitsugu, Kanako; Odo, Masashi; Watanabe, Hidetaka; Igata, Toshikatsu; Noguchi, Hiromitsu

2014-01-01

A 28-year-old man undergoing treatment for hemophagocytic syndrome developed Paecilomyces lilacinus infection in skin ulcers on the face and in the tracheotomy stoma. While his bone marrow was suppressed by chemotherapy with dexamethasone, cyclosporin and etoposide for hemophagocytic syndrome, dental infection led to subacute necrotizing fasciitis caused by Pseudomonas aeruginosa on the right side of the face, resulting in a large area of soft tissue defects. Etoposide was discontinued, and prophylactic treatment with itraconazole was initiated. The ulcers resulting from necrotizing fasciitis were treated conservatively using trafermin and alprostadil alfadex ointment 0.003 %, and near-complete re-epithelialization occurred, except on the right lower eyelid, right buccal mucosa and perioral area. However, 6 weeks later, pustules/crusts started to form and break down repeatedly, leading to expansion of tissue defects on the face. Direct microscopic examination revealed fungal elements, and fungal culture identified Paecilomyces lilacinus suspicious twice some other day. Based on DNA extraction from the isolated fungus, this fungal strain was identified as Paecilomyces lilacinus. Cyclosporin and itraconazole were discontinued, and treatment with liposomal amphotericin B and a tapering dose of steroids was initiated. Cure was achieved in approximately 2.5 months after treatment initiation, and no relapse has been observed. The most important factor that ultimately contributed to the resolution of fungal infection might have been release of immunosuppression by discontinuing cyclosporin and tapering steroids.

Management of erectile dysfunction post-radical prostatectomy

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Saleh A

2015-02-01

Full Text Available Alan Saleh, Hamid Abboudi, MB Ghazal-Aswad, Erik K Mayer, Justin A Vale Division of Surgery and Cancer, Imperial College Healthcare NHS Trust, St Mary's Hospital, London, UK Abstract: Radical prostatectomy is a commonly performed procedure for the treatment of localized prostate cancer. One of the long-term complications is erectile dysfunction. There is little consensus on the optimal management; however, it is agreed that treatment must be prompt to prevent fibrosis and increase oxygenation of penile tissue. It is vital that patient expectations are discussed, a realistic time frame of treatment provided, and treatment started as close to the prostatectomy as possible. Current treatment regimens rely on phosphodiesterase 5 inhibitors as a first-line therapy, with vacuum erection devices and intraurethral suppositories of alprostadil as possible treatment combination options. With nonresponders to these therapies, intracavernosal injections are resorted to. As a final measure, patients undergo the highly invasive penile prosthesis implantation. There is no uniform, objective treatment program for erectile dysfunction post-radical prostatectomy. Management plans are based on poorly conducted and often underpowered studies in combination with physician and patient preferences. They involve the aforementioned drugs and treatment methods in different sequences and doses. Prospective treatments include dietary supplements and gene therapy, which have shown promise with there proposed mechanisms of improving erectile function but are yet to be applied successfully in human patients. Keywords: erectile dysfunction, phosphodiesterase 5 inhibitors, vacuum erection devices, intraurethral suppositories, intracavernosal injections

Simultaneous determination of carboprost methylate and its active metabolite carboprost in dog plasma by liquid chromatography-tandem mass spectrometry with positive/negative ion-switching electrospray ionization and its application to a pharmacokinetic study.

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Yin, Lei; Meng, Xiangjun; Zhou, Xiaotong; Zhang, Tinglan; Sun, Heping; Yang, Zhichao; Yang, Bo; Xiao, Ning; Fawcett, J Paul; Yang, Yan; Gu, Jingkai

2015-08-15

A liquid chromatography-tandem mass spectrometric (LC-MS/MS) method using positive/negative electrospray ionization (ESI) switching for the simultaneous quantitation of carboprost methylate and carboprost in dog plasma has been developed and validated. After screening, the esterase inhibitor, dichlorvos was added to the whole blood at a ratio of 1:99 (v/v) to stabilize carboprost methylate during blood collection, sample storage and LLE. Indomethacin was added to plasma to inhibit prostaglandins synthesis after sampling. After liquid-liquid extraction of 500μL plasma with ethyl ether-dichloromethane (75:25, v/v), analytes and internal standard (IS), alprostadil-d4, were chromatographed on a CAPCELL PAK Phenyl column (150×2.0mm, 5μm) using acetonitrile-5mM ammonium acetate as mobile phase. Carboprost methylate was detected by positive ion electrospray ionization followed by multiple reaction monitoring (MRM) of the transition at m/z 400.5→329.3; the carboprost and IS were detected by negative ion electrospray ionization followed by MRM of the transitions at m/z 367.2→323.2, and 357.1→321.2, respectively. The method was linear for both analytes in the concentration range 0.05-30ng/mL with intra- and inter-day precisions (as relative standard deviation) of ≤6.75% and accuracy (as relative error) of ≤7.21% and limit of detection (LOD) values were 10 and 20pg/mL, respectively. The method was successfully applied to a pharmacokinetic study of the analytes in beagle dogs after intravaginal administration of a suppository containing 0.5mg carboprost methylate. Copyright © 2015 Elsevier B.V. All rights reserved.