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Development and validation of a UPLC–MS/MS assay for the determination of gemcitabine and its L-carnitine ester derivative in rat plasma and its application in oral pharmacokinetics

A simple and rapid UPLC–MS/MS method to simultaneously determine gemcitabine and its L-carnitine ester derivative (2'-deoxy-2', 2'-difluoro-N-((4-amino-4-oxobutanoyl) oxy)-4-(trimethyl amm-onio) butanoate-cytidine, JDR) in rat plasma was developed and validated. The conventional plasm...

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Autores principales: Wang, Gang, Zhao, Dongyang, Chen, Hongxiang, Ding, Dawei, Kou, Longfa, Sun, Lifang, Hao, Chenxia, Li, Xincong, Jia, Kai, Kan, Qiming, Liu, Xiaohong, He, Zhonggui, Sun, Jin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Shenyang Pharmaceutical University 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7032160/
https://www.ncbi.nlm.nih.gov/pubmed/32104361
http://dx.doi.org/10.1016/j.ajps.2017.01.001
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author Wang, Gang
Zhao, Dongyang
Chen, Hongxiang
Ding, Dawei
Kou, Longfa
Sun, Lifang
Hao, Chenxia
Li, Xincong
Jia, Kai
Kan, Qiming
Liu, Xiaohong
He, Zhonggui
Sun, Jin
author_facet Wang, Gang
Zhao, Dongyang
Chen, Hongxiang
Ding, Dawei
Kou, Longfa
Sun, Lifang
Hao, Chenxia
Li, Xincong
Jia, Kai
Kan, Qiming
Liu, Xiaohong
He, Zhonggui
Sun, Jin
author_sort Wang, Gang
collection PubMed
description A simple and rapid UPLC–MS/MS method to simultaneously determine gemcitabine and its L-carnitine ester derivative (2'-deoxy-2', 2'-difluoro-N-((4-amino-4-oxobutanoyl) oxy)-4-(trimethyl amm-onio) butanoate-cytidine, JDR) in rat plasma was developed and validated. The conventional plasma sample preparation method of nucleoside analogues is solid-phase extraction (SPE) which is time-consuming and cost-expensive. In this study, gradient elution with small particles size solid phase was applied to effectively separate gemcitabine and JDR, and protein precipitation pretreatment was adopted to remove plasma protein and extract the analytes with high recovery(>81%). Method validation was performed as per the FDA guidelines, and the standard curves were found to be linear in the range of 5–4000 ng/ml for JDR and 4–4000 ng/ml for gemcitabine, respectively. The lower limit of quantitation (LLOQ) of gemcitabine and JDR was 4 and 5 ng/ml, respectively. The intra-day and inter-day precision and accuracy results were within the acceptable limits. Finally, the developed method was successfully applied to investigate the pharmacokinetic studies of JDR and gemcitabine after oral administration to rats.
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spelling pubmed-70321602020-02-26 Development and validation of a UPLC–MS/MS assay for the determination of gemcitabine and its L-carnitine ester derivative in rat plasma and its application in oral pharmacokinetics Wang, Gang Zhao, Dongyang Chen, Hongxiang Ding, Dawei Kou, Longfa Sun, Lifang Hao, Chenxia Li, Xincong Jia, Kai Kan, Qiming Liu, Xiaohong He, Zhonggui Sun, Jin Asian J Pharm Sci Original Research Article A simple and rapid UPLC–MS/MS method to simultaneously determine gemcitabine and its L-carnitine ester derivative (2'-deoxy-2', 2'-difluoro-N-((4-amino-4-oxobutanoyl) oxy)-4-(trimethyl amm-onio) butanoate-cytidine, JDR) in rat plasma was developed and validated. The conventional plasma sample preparation method of nucleoside analogues is solid-phase extraction (SPE) which is time-consuming and cost-expensive. In this study, gradient elution with small particles size solid phase was applied to effectively separate gemcitabine and JDR, and protein precipitation pretreatment was adopted to remove plasma protein and extract the analytes with high recovery(>81%). Method validation was performed as per the FDA guidelines, and the standard curves were found to be linear in the range of 5–4000 ng/ml for JDR and 4–4000 ng/ml for gemcitabine, respectively. The lower limit of quantitation (LLOQ) of gemcitabine and JDR was 4 and 5 ng/ml, respectively. The intra-day and inter-day precision and accuracy results were within the acceptable limits. Finally, the developed method was successfully applied to investigate the pharmacokinetic studies of JDR and gemcitabine after oral administration to rats. Shenyang Pharmaceutical University 2017-09 2017-01-09 /pmc/articles/PMC7032160/ /pubmed/32104361 http://dx.doi.org/10.1016/j.ajps.2017.01.001 Text en © 2017 Production and hosting by Elsevier B.V. on behalf of Shenyang Pharmaceutical University. http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Original Research Article
Wang, Gang
Zhao, Dongyang
Chen, Hongxiang
Ding, Dawei
Kou, Longfa
Sun, Lifang
Hao, Chenxia
Li, Xincong
Jia, Kai
Kan, Qiming
Liu, Xiaohong
He, Zhonggui
Sun, Jin
Development and validation of a UPLC–MS/MS assay for the determination of gemcitabine and its L-carnitine ester derivative in rat plasma and its application in oral pharmacokinetics
title Development and validation of a UPLC–MS/MS assay for the determination of gemcitabine and its L-carnitine ester derivative in rat plasma and its application in oral pharmacokinetics
title_full Development and validation of a UPLC–MS/MS assay for the determination of gemcitabine and its L-carnitine ester derivative in rat plasma and its application in oral pharmacokinetics
title_fullStr Development and validation of a UPLC–MS/MS assay for the determination of gemcitabine and its L-carnitine ester derivative in rat plasma and its application in oral pharmacokinetics
title_full_unstemmed Development and validation of a UPLC–MS/MS assay for the determination of gemcitabine and its L-carnitine ester derivative in rat plasma and its application in oral pharmacokinetics
title_short Development and validation of a UPLC–MS/MS assay for the determination of gemcitabine and its L-carnitine ester derivative in rat plasma and its application in oral pharmacokinetics
title_sort development and validation of a uplc–ms/ms assay for the determination of gemcitabine and its l-carnitine ester derivative in rat plasma and its application in oral pharmacokinetics
topic Original Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7032160/
https://www.ncbi.nlm.nih.gov/pubmed/32104361
http://dx.doi.org/10.1016/j.ajps.2017.01.001
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