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Enhanced Extraction Technique of Omarigliptin from Human Plasma—Applied to Biological Samples from Healthy Human Volunteers

Enhancing drug extraction from human plasma is a challenging approach that critically affects pharmacokinetic and any further clinical studies based on the drug C(min) and C(max) values. It also has a serious impact on the sensitivity and the lower limit of quantification (LLOQ) value of the bio-ana...

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Autores principales: Mowaka, Shereen, Ashoush, Nermeen, Tadros, Mariam, El Zahar, Noha, Ayoub, Bassam
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7570897/
https://www.ncbi.nlm.nih.gov/pubmed/32942678
http://dx.doi.org/10.3390/molecules25184232
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author Mowaka, Shereen
Ashoush, Nermeen
Tadros, Mariam
El Zahar, Noha
Ayoub, Bassam
author_facet Mowaka, Shereen
Ashoush, Nermeen
Tadros, Mariam
El Zahar, Noha
Ayoub, Bassam
author_sort Mowaka, Shereen
collection PubMed
description Enhancing drug extraction from human plasma is a challenging approach that critically affects pharmacokinetic and any further clinical studies based on the drug C(min) and C(max) values. It also has a serious impact on the sensitivity and the lower limit of quantification (LLOQ) value of the bio-analytical methods. An advanced liquid chromatography tandem mass spectrometry (LC-MS/MS) bio-analytical method of omarigliptin (25–1000 nM) was established in human plasma using one-step liquid-liquid extraction. Alogliptin was used as an internal standard (IS) to attain good recovery and reproducibility while reducing the effects of the matrix. Enhanced plasma extraction of omarigliptin was successfully achieved with tertiary butyl methyl ether—diethyl ether (TBME-DEE) mixture as the extracting solvent, while using acetonitrile as the diluent solvent for the IS to effectively decrease the formed emulsion. Multiple Reaction Monitoring (MRM) of the transition pairs of m/z 399.2 to 153.0 for omarigliptin and m/z 340.2 to 116.0 for alogliptin was employed in positive Electro Spray Ionization (ESI) mode. Human plasma samples were collected after 1.5 h (t(max)) of Marizev(®) (12.5 mg) tablets administration to healthy human volunteers showing average concentration of 292.18 nM. Validation results were all satisfactory including successful stability studies with bias below 12%. The proposed study will be valuable for ethnicity comparison studies that will be commenced on omarigliptin in Egypt by the authors in prospective study, following the FDA recommends, to evaluate possible sub-group dissimilarities that include pharmacokinetic parameters.
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spelling pubmed-75708972020-10-28 Enhanced Extraction Technique of Omarigliptin from Human Plasma—Applied to Biological Samples from Healthy Human Volunteers Mowaka, Shereen Ashoush, Nermeen Tadros, Mariam El Zahar, Noha Ayoub, Bassam Molecules Article Enhancing drug extraction from human plasma is a challenging approach that critically affects pharmacokinetic and any further clinical studies based on the drug C(min) and C(max) values. It also has a serious impact on the sensitivity and the lower limit of quantification (LLOQ) value of the bio-analytical methods. An advanced liquid chromatography tandem mass spectrometry (LC-MS/MS) bio-analytical method of omarigliptin (25–1000 nM) was established in human plasma using one-step liquid-liquid extraction. Alogliptin was used as an internal standard (IS) to attain good recovery and reproducibility while reducing the effects of the matrix. Enhanced plasma extraction of omarigliptin was successfully achieved with tertiary butyl methyl ether—diethyl ether (TBME-DEE) mixture as the extracting solvent, while using acetonitrile as the diluent solvent for the IS to effectively decrease the formed emulsion. Multiple Reaction Monitoring (MRM) of the transition pairs of m/z 399.2 to 153.0 for omarigliptin and m/z 340.2 to 116.0 for alogliptin was employed in positive Electro Spray Ionization (ESI) mode. Human plasma samples were collected after 1.5 h (t(max)) of Marizev(®) (12.5 mg) tablets administration to healthy human volunteers showing average concentration of 292.18 nM. Validation results were all satisfactory including successful stability studies with bias below 12%. The proposed study will be valuable for ethnicity comparison studies that will be commenced on omarigliptin in Egypt by the authors in prospective study, following the FDA recommends, to evaluate possible sub-group dissimilarities that include pharmacokinetic parameters. MDPI 2020-09-15 /pmc/articles/PMC7570897/ /pubmed/32942678 http://dx.doi.org/10.3390/molecules25184232 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Mowaka, Shereen
Ashoush, Nermeen
Tadros, Mariam
El Zahar, Noha
Ayoub, Bassam
Enhanced Extraction Technique of Omarigliptin from Human Plasma—Applied to Biological Samples from Healthy Human Volunteers
title Enhanced Extraction Technique of Omarigliptin from Human Plasma—Applied to Biological Samples from Healthy Human Volunteers
title_full Enhanced Extraction Technique of Omarigliptin from Human Plasma—Applied to Biological Samples from Healthy Human Volunteers
title_fullStr Enhanced Extraction Technique of Omarigliptin from Human Plasma—Applied to Biological Samples from Healthy Human Volunteers
title_full_unstemmed Enhanced Extraction Technique of Omarigliptin from Human Plasma—Applied to Biological Samples from Healthy Human Volunteers
title_short Enhanced Extraction Technique of Omarigliptin from Human Plasma—Applied to Biological Samples from Healthy Human Volunteers
title_sort enhanced extraction technique of omarigliptin from human plasma—applied to biological samples from healthy human volunteers
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7570897/
https://www.ncbi.nlm.nih.gov/pubmed/32942678
http://dx.doi.org/10.3390/molecules25184232
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