scholarly journals LC-MS method for determination of olmesartan in human plasma

2015 ◽  
Author(s):  
Jacek Musijowski ◽  
Edyta Piórkowska ◽  
Katarzyna Buś - Kwaśnik ◽  
Agnieszka Tycz ◽  
Piotr J. Rudzki
Keyword(s):  
Blood Pressure ◽  
Human Plasma ◽  
High Blood Pressure ◽  
Active Form ◽  
Olmesartan Medoxomil ◽  
European Medicines Agency ◽  
Pharmacokinetic Studies ◽  
Angiotensin Ii Receptor ◽  
Validation Parameters

Olmesartan belongs to a class of drugs called angiotensin II receptor blockers (ARBs). It works by relaxing blood vessels so that blood can flow more easily and is used to treat high blood pressure (hypertension). Lowering high blood pressure helps prevent strokes, heart attacks, and kidney problems. Olmesartan medoxomil is an ester prodrug that is hydrolysed during absorption from gastrointestinal tract to the active form olmesartan. Due to rapid metabolism determination of the concentration of the prodrug in plasma is impossible. Previous human pharmacokinetic studies indicated that olmesartan is the only metabolite of olmesartan medoxomil. The aim of the study was to develop a method for the determination of olmesartan in human plasma. The developed LC-MS method is linear within the range of 5.00-2500.00 ng/mL which is suitable for pharmacokinetic studies after administration of 40 mg olmesartan medoxomil single oral dose. The sample preparation procedure is fast and allows examination of large numbers of samples in a short time. The method was validated according to European Medicines Agency (EMA) and Food and Drug Administration (FDA) guidelines, in compliance with the principles of Good Laboratory Practice (GLP). All of the validation parameters met acceptance criteria and the method was successfully applied in the pharmacokinetic study in humans.

scholarly journals LC-MS method for determination of olmesartan in human plasma

2015 ◽  
Author(s):  
Jacek Musijowski ◽  
Edyta Piórkowska ◽  
Katarzyna Buś - Kwaśnik ◽  
Agnieszka Tycz ◽  
Piotr J. Rudzki
Keyword(s):  
Blood Pressure ◽  
Human Plasma ◽  
High Blood Pressure ◽  
Active Form ◽  
Olmesartan Medoxomil ◽  
European Medicines Agency ◽  
Pharmacokinetic Studies ◽  
Angiotensin Ii Receptor ◽  
Validation Parameters

Olmesartan belongs to a class of drugs called angiotensin II receptor blockers (ARBs). It works by relaxing blood vessels so that blood can flow more easily and is used to treat high blood pressure (hypertension). Lowering high blood pressure helps prevent strokes, heart attacks, and kidney problems. Olmesartan medoxomil is an ester prodrug that is hydrolysed during absorption from gastrointestinal tract to the active form olmesartan. Due to rapid metabolism determination of the concentration of the prodrug in plasma is impossible. Previous human pharmacokinetic studies indicated that olmesartan is the only metabolite of olmesartan medoxomil. The aim of the study was to develop a method for the determination of olmesartan in human plasma. The developed LC-MS method is linear within the range of 5.00-2500.00 ng/mL which is suitable for pharmacokinetic studies after administration of 40 mg olmesartan medoxomil single oral dose. The sample preparation procedure is fast and allows examination of large numbers of samples in a short time. The method was validated according to European Medicines Agency (EMA) and Food and Drug Administration (FDA) guidelines, in compliance with the principles of Good Laboratory Practice (GLP). All of the validation parameters met acceptance criteria and the method was successfully applied in the pharmacokinetic study in humans.

scholarly journals Influence of hydroxybosentan on determination of bosentan in human plasma

2015 ◽  
Author(s):  
Edyta Gilant ◽  
Katarzyna Buś - Kwaśnik ◽  
Izabela Domel ◽  
Michał Kaza ◽  
Piotr J. Rudzki
Keyword(s):  
Human Plasma ◽  
Maximum Concentration ◽  
High Performance ◽  
Internal Standard ◽  
European Medicines Agency ◽  
Bioanalytical Method ◽  
Elimination Half ◽  
Validation Parameters ◽  
Pharmacologically Active

Bosentan is a drug used in the treatment of pulmonary arterial hypertension. Evaluation of bosentan pharmacokinetics is an important step of the drug development. The aim of our study was to evaluate bioanalytical method reliability by assessing the influence of metabolite on the determination of bosentan in human plasma. In human body, bosentan is converted to three metabolites. Hydroxybosentan is an only pharmacologically active metabolite and its maximum concentration in plasma reaches 5-8% of the bosentan’s maximum concentration. Hydroxybosentan’s elimination half-life was reported to be very similar to that of bosentan (5-6 h) or slightly greater (6-14 h). It was observed that times to reach the maximum concentrations are similar for both compounds. Combination of high-performance liquid chromatography with UV-Vis detection and liquid-liquid extraction enabled to was determine bosentan in human plasma in the range of 50-4000 ng∙mL-1. During the method validation, metabolite back-conversion was studied using human plasma samples spkied with hydroxybosentan to obtain concentration of 500 ng·mL-1. Additionally, the influence of metabolite on extraction of bosentan and the internal standard was assessed. We found that there was no influence of metabolite on determination of bosentan in developed bioanalytical method. The method was validated according to European Medicines Agency (EMA) and Food and Drug Administration (FDA) guidelines, in compliance with the principles of Good Laboratory Practice (GLP). All of the validation parameters met acceptance criteria what confirmed method’s reliability.

scholarly journals Influence of hydroxybosentan on determination of bosentan in human plasma

2015 ◽  
Author(s):  
Edyta Gilant ◽  
Katarzyna Buś - Kwaśnik ◽  
Izabela Domel ◽  
Michał Kaza ◽  
Piotr J. Rudzki
Keyword(s):  
Human Plasma ◽  
Maximum Concentration ◽  
High Performance ◽  
Internal Standard ◽  
European Medicines Agency ◽  
Bioanalytical Method ◽  
Elimination Half ◽  
Validation Parameters ◽  
Pharmacologically Active

Bosentan is a drug used in the treatment of pulmonary arterial hypertension. Evaluation of bosentan pharmacokinetics is an important step of the drug development. The aim of our study was to evaluate bioanalytical method reliability by assessing the influence of metabolite on the determination of bosentan in human plasma. In human body, bosentan is converted to three metabolites. Hydroxybosentan is an only pharmacologically active metabolite and its maximum concentration in plasma reaches 5-8% of the bosentan’s maximum concentration. Hydroxybosentan’s elimination half-life was reported to be very similar to that of bosentan (5-6 h) or slightly greater (6-14 h). It was observed that times to reach the maximum concentrations are similar for both compounds. Combination of high-performance liquid chromatography with UV-Vis detection and liquid-liquid extraction enabled to was determine bosentan in human plasma in the range of 50-4000 ng∙mL-1. During the method validation, metabolite back-conversion was studied using human plasma samples spkied with hydroxybosentan to obtain concentration of 500 ng·mL-1. Additionally, the influence of metabolite on extraction of bosentan and the internal standard was assessed. We found that there was no influence of metabolite on determination of bosentan in developed bioanalytical method. The method was validated according to European Medicines Agency (EMA) and Food and Drug Administration (FDA) guidelines, in compliance with the principles of Good Laboratory Practice (GLP). All of the validation parameters met acceptance criteria what confirmed method’s reliability.

scholarly journals Development and Validation of Valganciclovir and its Active Metabolite Ganciclovir Determination in Human Plasma by HPLC-UV Method

2020 ◽  
Vol 9 (2) ◽  
pp. 133-139
Author(s):  
T. N. Komarov ◽  
I. E. Shohin ◽  
O. A. Miskiv ◽  
D. S. Bogdanova ◽  
A. V. Aleshina ◽  
...  
Keyword(s):  
Quantitative Determination ◽  
Simultaneous Determination ◽  
Human Plasma ◽  
Active Metabolite ◽  
Protein Precipitation ◽  
Human Blood Plasma ◽  
Pharmacokinetic Studies ◽  
Validation Parameters ◽  
Development And Validation

Introduction. Viral infections are a serious problem that occurs during the use of immunosuppressants in preparation for organ transplantation and in the postoperative period. Cytomegalovirus (CMV) infection is one of the main causes of diseases in people with weakened immune systems. It has a direct impact on one’s body and makes it more likely to reject a transplanted organ. Antiviral drugs are used to treat and prevent this infectious disease. Valganciclovir is a prodrug whose active metabolite is ganciclovir. Valganciclovir is the drug of choice in the treatment of CMV infections. Currently, there are no researches on the matter of simultaneous determination of both valganciclovir and ganciclovir in human blood plasma by means of high-performance liquid chromatography (HPLC) with ultraviolet detection. This research delivers a thorough description of development and validation of a particular method for simultaneous determination of valganciclovir and ganciclovir in the plasma after sample preparation by the method of protein precipitation.Aim. The aim of this study is to develop method for the quantitative determination of valganciclovir and its active metabolite ganciclovir in human plasma by HPLC-UV for pharmacokinetic studies.Materials and methods. Quantitative determination of tadalafil in plasma by HPLC-UV. A sample was prepared using protein precipitation.Results and discussion. This method was validated by next validation parameters: selectivity, matrix effect, calibration curve, accuracy, precision, lower limit of quantification, carry-over and stability.Conclusion. The method of the quantitative determination of valganciclovir and its active metabolite ganciclovir in human plasma was developed and validated by HPLC-UV. The analytical range of the was 5,0–1000,0 ng/ml for valganciclovir and 100,0–10000,0 ng/ml for ganciclovir in plasma. Method could be applied to determination of valganciclovir and ganciclovir in plasma for PK and BE studies.

scholarly journals Development and Validation of Tadalafil Determination in Human Plasma by HPLC-MS Method

2019 ◽  
Vol 8 (2) ◽  
pp. 108-114
Author(s):  
D. S. Bogdanova ◽  
T. N. Komarov ◽  
I. E. Shohin ◽  
E. S. Melnikov ◽  
O. A. Miskiv ◽  
...  
Keyword(s):  
Quantitative Determination ◽  
Human Plasma ◽  
Solid Phase ◽  
Protein Precipitation ◽  
Clinical Samples ◽  
Pharmacokinetic Studies ◽  
Limit Of Quantification ◽  
Validation Parameters ◽  
Tandem Mass Spectrometric

Introduction. Tadalafil is a drug used to treat erectile dysfunction. For the quantitative determination of tadalafil in human plasma are used methods of high performance liquid chromatography with ultraviolet and tandem mass spectrometric detection, during the analytical part of pharmacokinetic studies. In the majority of the considered methods the method of liquid-liquid extraction and the method of solid-phase extraction are used, these methods are difficult and expensive. Therefore, the method of protein precipitation was considered as sample preparation. This method is simple and there is important to analysis a lot of clinical samples in bioequivalence studies.Aim. The aim of this study is to develop method for the quantitative determination of tadalafil in human plasma by HPLC-MS for the analytical part of pharmacokinetic studies.Materials and methods. Quantitative determination of tadalafil in plasma by HPLC-MS. A sample was prepared using acetonitrile protein precipitation.Results and discussion. This method was validated by next validation parameters: selectivity, matrix effect, calibration curve, accuracy, precision, lower limit of quantification, carry-over and stability.Conclusion. The method of the quantitative determination of tadalafil in human plasma was developed and validated by HPLC-MS. The analytical range of the was 5,00–1000,00 ng/ml tadalafil in plasma. Method could be applied to determination of tadalafil in plasma for PK and BE studies.

Hypertension: Focus on Olmesartan Medoxomil

2009 ◽  
Vol 1 ◽  
pp. CMT.S2206 ◽  
Author(s):  
Allison M. Bell ◽  
Diane Nykamp
Keyword(s):  
Blood Pressure ◽  
Angiotensin Receptor Blockers ◽  
Active Form ◽  
Antihypertensive Agents ◽  
Olmesartan Medoxomil ◽  
Pharmacokinetic Profile ◽  
Angiotensin Receptor ◽  
Angiotensin Ii Receptor ◽  
Pharmacodynamic Profile ◽  
Isozyme System

Hypertension is the leading cause of stroke, heart failure, and ischemic heart disease. One of the key regulators of blood pressure is the renin-angiotensin aldosterone system (RAAS). Olmesartan medoxomil, an angiotensin receptor blocker (ARB), counteracts some of the primary effects of the RAAS by selectively and irreversibly binding to the type 1 angiotensin II receptor (AT1-R). The pharmacokinetic profile of this ARB allows for the convenience of one a day dosing. The pharmacodynamic profile of olmesartan is favorable because it is neither metabolized by, induces, nor inhibits the CYP450 isozyme system. The metabolism of the prodrug to the active form occurs in the gut by the enzyme arylesterase. No further metabolism and a lack of interaction with the CYP450 isozyme system leads to very few drug interactions with olmesartan medoxomil. Numerous studies have been conducted to evaluate the efficacy, safety, and tolerability of olmesartan medoxomil. Studies have been conducted to compare olmesartan medoxomil to other angiotensin receptor blockers. The efficacy of olmesartan medoxomil has been compared to other classes of antihypertensive agents. Results of all trials have proven non-inferiority of olmesartan medoxomil to other antihypertensive agents; some studies have shown superior blood pressure control provided by olmesartan medoxomil when starting dosages are evaluated. Overall, olmesartan medoxomil has the potential to facilitate the achievement of blood pressure goals, enhance compliance with a once daily dosing regimen, and is associated with minimal side effects. Olmesartan medoxomil has been proven to be a safe and effective antihypertensive drug when compared to other ARBs and other antihypertensive agents.

AN EFFICIENT HPLC-UV METHOD FOR THE QUANTITATIVE DETERMINATION OF CEFADROXIL IN HUMAN PLASMA AND ITS APPLICATION IN PHARMACOKINETIC STUDIES

2012 ◽  
Vol 35 (13) ◽  
pp. 1871-1881 ◽  
Author(s):  
Eunice Kazue Kano ◽  
Cristina Helena dos Reis Serra ◽  
Eunice Emiko Mori Koono ◽  
Kazuo Fukuda ◽  
Valentina Porta
Keyword(s):  
Quantitative Determination ◽  
Human Plasma ◽  
Pharmacokinetic Studies

Simultaneous determination of novel ketolide antibiotic nafithromycin and its major metabolite in human plasma using liquid chromatography tandem mass spectrometry

Bioanalysis ◽  
2019 ◽  
Vol 11 (19) ◽  
pp. 1767-1776
Author(s):  
Kiran R Patil ◽  
Ravindra D Yeole ◽  
Marcel de Zwart ◽  
Peter Pruim
Keyword(s):  
Phase I ◽  
Human Plasma ◽  
Internal Standard ◽  
Pharmacokinetic Studies ◽  
Simultaneous Quantification ◽  
Chromatography Tandem Mass Spectrometry ◽  
Liquid Chromatography Tandem Mass ◽  
Us Fda ◽  
Standard Protein

Aim: A sensitive method to quantify nafithromycin and its N-desmethyl metabolite in human plasma was necessary for Phase I pharmacokinetic studies. Methodology: A precise and accurate LC–MS/MS bioanalytical method has been developed and validated for the simultaneous quantification of nafithromycin (NFT, WCK 4873) and N-desmethyl metabolite (M1, WCK 4978) in human plasma. Clarithromycin was used as an internal standard. Protein precipitation technique was used as sample preparation approach. The calibration curve was linear (r ≥ 0.99) over the concentration range of 10–5000 ng/ml for NFT and M1. Method was validated as per US FDA guideline. Conclusion: The proposed method was successfully applied for determination of plasma levels of the NFT and M1 during Phase I clinical studies.

Determination of total or free cefazolin and metronidazole in human plasma or interstitial fluid by HPLC-UV for pharmacokinetic studies in man

2019 ◽  
Vol 1118-1119 ◽  
pp. 51-54 ◽  
Author(s):  
Christoph Dorn ◽  
Alexander Kratzer ◽  
Selina Schießer ◽  
Frieder Kees ◽  
Hermann Wrigge ◽  
...  
Keyword(s):  
Human Plasma ◽  
Interstitial Fluid ◽  
Pharmacokinetic Studies
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