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Analysis of Vipadenant and Its In Vitro and In Vivo Metabolites via Liquid Chromatography-Quadrupole-Time-of-Flight Mass Spectrometry

A simple and sensitive liquid chromatography–quadrupole-time-of-flight–mass spectrometric (LC-QTOF-MS) assay has been developed for the evaluation of drug metabolism and pharmacokinetics (PK) properties of vipadenant in rat, a selective A2a receptor antagonist as one of the novel immune checkpoint i...

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Autores principales: Shin, Seok-Ho, Park, Min-Ho, Byeon, Jin-Ju, Lee, Byeong ill, Park, Yuri, Kim, Nahye, Choi, Jangmi, Shin, Young G.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6321172/
https://www.ncbi.nlm.nih.gov/pubmed/30513962
http://dx.doi.org/10.3390/pharmaceutics10040260
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author Shin, Seok-Ho
Park, Min-Ho
Byeon, Jin-Ju
Lee, Byeong ill
Park, Yuri
Kim, Nahye
Choi, Jangmi
Shin, Young G.
author_facet Shin, Seok-Ho
Park, Min-Ho
Byeon, Jin-Ju
Lee, Byeong ill
Park, Yuri
Kim, Nahye
Choi, Jangmi
Shin, Young G.
author_sort Shin, Seok-Ho
collection PubMed
description A simple and sensitive liquid chromatography–quadrupole-time-of-flight–mass spectrometric (LC-QTOF-MS) assay has been developed for the evaluation of drug metabolism and pharmacokinetics (PK) properties of vipadenant in rat, a selective A2a receptor antagonist as one of the novel immune checkpoint inhibitors. A simple protein precipitation method using acetonitrile was used for the sample preparation and the pre-treated samples were separated by a reverse-phase C18 column. The calibration curve was evaluated in the range of 3.02 ~ 2200 ng/mL and the quadratic regression (weighted 1/concentration) was used for the best fit of the curve with a correlation coefficient ≥0.997. The in vivo PK studies in rats showed that vipadenant bioavailability was 30.4 ± 8.9% with a low to moderate drug clearance. In addition, in vitro/in vivo metabolite profiles in rat were also explored. Five different metabolites were observed in our experimental conditions and the major metabolites were different between in vitro and in vivo conditions. As far as we know, there has been no report on the development of quantitative methods for its PK samples nor the identification of its metabolites since vipadenant was developed. Therefore, this paper would be very useful to better understand the pharmacokinetic and drug metabolism properties of vipadenant in rat as well as other species.
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spelling pubmed-63211722019-01-11 Analysis of Vipadenant and Its In Vitro and In Vivo Metabolites via Liquid Chromatography-Quadrupole-Time-of-Flight Mass Spectrometry Shin, Seok-Ho Park, Min-Ho Byeon, Jin-Ju Lee, Byeong ill Park, Yuri Kim, Nahye Choi, Jangmi Shin, Young G. Pharmaceutics Article A simple and sensitive liquid chromatography–quadrupole-time-of-flight–mass spectrometric (LC-QTOF-MS) assay has been developed for the evaluation of drug metabolism and pharmacokinetics (PK) properties of vipadenant in rat, a selective A2a receptor antagonist as one of the novel immune checkpoint inhibitors. A simple protein precipitation method using acetonitrile was used for the sample preparation and the pre-treated samples were separated by a reverse-phase C18 column. The calibration curve was evaluated in the range of 3.02 ~ 2200 ng/mL and the quadratic regression (weighted 1/concentration) was used for the best fit of the curve with a correlation coefficient ≥0.997. The in vivo PK studies in rats showed that vipadenant bioavailability was 30.4 ± 8.9% with a low to moderate drug clearance. In addition, in vitro/in vivo metabolite profiles in rat were also explored. Five different metabolites were observed in our experimental conditions and the major metabolites were different between in vitro and in vivo conditions. As far as we know, there has been no report on the development of quantitative methods for its PK samples nor the identification of its metabolites since vipadenant was developed. Therefore, this paper would be very useful to better understand the pharmacokinetic and drug metabolism properties of vipadenant in rat as well as other species. MDPI 2018-12-03 /pmc/articles/PMC6321172/ /pubmed/30513962 http://dx.doi.org/10.3390/pharmaceutics10040260 Text en © 2018 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
Shin, Seok-Ho
Park, Min-Ho
Byeon, Jin-Ju
Lee, Byeong ill
Park, Yuri
Kim, Nahye
Choi, Jangmi
Shin, Young G.
Analysis of Vipadenant and Its In Vitro and In Vivo Metabolites via Liquid Chromatography-Quadrupole-Time-of-Flight Mass Spectrometry
title Analysis of Vipadenant and Its In Vitro and In Vivo Metabolites via Liquid Chromatography-Quadrupole-Time-of-Flight Mass Spectrometry
title_full Analysis of Vipadenant and Its In Vitro and In Vivo Metabolites via Liquid Chromatography-Quadrupole-Time-of-Flight Mass Spectrometry
title_fullStr Analysis of Vipadenant and Its In Vitro and In Vivo Metabolites via Liquid Chromatography-Quadrupole-Time-of-Flight Mass Spectrometry
title_full_unstemmed Analysis of Vipadenant and Its In Vitro and In Vivo Metabolites via Liquid Chromatography-Quadrupole-Time-of-Flight Mass Spectrometry
title_short Analysis of Vipadenant and Its In Vitro and In Vivo Metabolites via Liquid Chromatography-Quadrupole-Time-of-Flight Mass Spectrometry
title_sort analysis of vipadenant and its in vitro and in vivo metabolites via liquid chromatography-quadrupole-time-of-flight mass spectrometry
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6321172/
https://www.ncbi.nlm.nih.gov/pubmed/30513962
http://dx.doi.org/10.3390/pharmaceutics10040260
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