Simultaneous Determination of Schisandrin and Promethazine with Its Metabolite in Rat Plasma by HPLC-MS/MS and Its Application to a Pharmacokinetic Study

This study aimed to develop a selective, simple, and sensitive HPLC-MS/MS method for the simultaneous determination of schisandrin and promethazine (PMZ) with its metabolite in rat plasma, which was further used for a pharmacokinetic herb-drug interaction study. HPLC-MS/MS analyses were performed on...

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Main Authors: Sijia Gao, Xuelin Zhou, Liwei Lang, Honghong Liu, Jianyu Li, Haotian Li, Shizhang Wei, Dan Wang, Zhuo Xu, Huadan Cai, Yanling Zhao, Wenjun Zou
Format: Article
Language:English
Published: Wiley 2019-01-01
Series:International Journal of Analytical Chemistry
Online Access:http://dx.doi.org/10.1155/2019/3497045
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author Sijia Gao
Xuelin Zhou
Liwei Lang
Honghong Liu
Jianyu Li
Haotian Li
Shizhang Wei
Dan Wang
Zhuo Xu
Huadan Cai
Yanling Zhao
Wenjun Zou
author_facet Sijia Gao
Xuelin Zhou
Liwei Lang
Honghong Liu
Jianyu Li
Haotian Li
Shizhang Wei
Dan Wang
Zhuo Xu
Huadan Cai
Yanling Zhao
Wenjun Zou
author_sort Sijia Gao
collection DOAJ
description This study aimed to develop a selective, simple, and sensitive HPLC-MS/MS method for the simultaneous determination of schisandrin and promethazine (PMZ) with its metabolite in rat plasma, which was further used for a pharmacokinetic herb-drug interaction study. HPLC-MS/MS analyses were performed on an Agilent Technologies 1290 LC and a 6410 triple quadrupole mass spectrometer. The following parameters, the lower limit of quantification (LLOQ), calibration curve, accuracy, precision, stability, matrix effect, and recovery, were validated. The linear range of the developed method for PMZ, its metabolite promethazine sulfoxide (PMZSO), and schisandrin in rat plasma was 0.5–200 ng/mL (R2 > 0.995), with an LLOQ of 0.5 ng/mL, which completely met the determination requirements of biosamples. The intra- and interday precision (RSD, %) was below 13.31% (below 16.67% for the LLOQ) in various plasma, whose accuracy (bias, %) was from −8.52% to 11.40%, which were both within an acceptable range. This method was successfully applied to a pharmacokinetic herb-drug interaction study after oral administration of PMZ with or without S. chinensis water extract. The results demonstrated that coadministration with the S. chinensis water extract might affect the pharmacokinetic behaviors of PMZ. In turn, when taken together with PMZ, the pharmacokinetic parameters of schisandrin, the main active component of S. chinensis, were also affected. The method established in the current study was selective, simple, sensitive, and widely available with good linearity, high accuracy and precision, and a stable sample preparation process. Moreover, this analytical method provides a significant approach for the investigation of herb-drug interaction between S. chinensis and PMZ. The potential pharmacokinetic herb-drug interaction of PMZ- and schisandrin-containing preparations should be noted.
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spelling doaj-art-d8d906de06e64a77a67e03b280941c0e2025-08-20T02:20:58ZengWileyInternational Journal of Analytical Chemistry1687-87601687-87792019-01-01201910.1155/2019/34970453497045Simultaneous Determination of Schisandrin and Promethazine with Its Metabolite in Rat Plasma by HPLC-MS/MS and Its Application to a Pharmacokinetic StudySijia Gao0Xuelin Zhou1Liwei Lang2Honghong Liu3Jianyu Li4Haotian Li5Shizhang Wei6Dan Wang7Zhuo Xu8Huadan Cai9Yanling Zhao10Wenjun Zou11College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, ChinaDepartment of Pharmacology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, ChinaThe Center of Clinical Research, The Fifth Medical Center of PLA General Hospital, Beijing 100039, ChinaDepartment of Integrative Medical Center, The Fifth Medical Center of PLA General Hospital, Beijing 100039, ChinaDepartment of Integrative Medical Center, The Fifth Medical Center of PLA General Hospital, Beijing 100039, ChinaDepartment of Pharmacy, The Fifth Medical Center of PLA General Hospital, Beijing 100039, ChinaDepartment of Pharmacy, The Fifth Medical Center of PLA General Hospital, Beijing 100039, ChinaCollege of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, ChinaCollege of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, ChinaDepartment of Pharmacy, The Fifth Medical Center of PLA General Hospital, Beijing 100039, ChinaDepartment of Pharmacy, The Fifth Medical Center of PLA General Hospital, Beijing 100039, ChinaCollege of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, ChinaThis study aimed to develop a selective, simple, and sensitive HPLC-MS/MS method for the simultaneous determination of schisandrin and promethazine (PMZ) with its metabolite in rat plasma, which was further used for a pharmacokinetic herb-drug interaction study. HPLC-MS/MS analyses were performed on an Agilent Technologies 1290 LC and a 6410 triple quadrupole mass spectrometer. The following parameters, the lower limit of quantification (LLOQ), calibration curve, accuracy, precision, stability, matrix effect, and recovery, were validated. The linear range of the developed method for PMZ, its metabolite promethazine sulfoxide (PMZSO), and schisandrin in rat plasma was 0.5–200 ng/mL (R2 > 0.995), with an LLOQ of 0.5 ng/mL, which completely met the determination requirements of biosamples. The intra- and interday precision (RSD, %) was below 13.31% (below 16.67% for the LLOQ) in various plasma, whose accuracy (bias, %) was from −8.52% to 11.40%, which were both within an acceptable range. This method was successfully applied to a pharmacokinetic herb-drug interaction study after oral administration of PMZ with or without S. chinensis water extract. The results demonstrated that coadministration with the S. chinensis water extract might affect the pharmacokinetic behaviors of PMZ. In turn, when taken together with PMZ, the pharmacokinetic parameters of schisandrin, the main active component of S. chinensis, were also affected. The method established in the current study was selective, simple, sensitive, and widely available with good linearity, high accuracy and precision, and a stable sample preparation process. Moreover, this analytical method provides a significant approach for the investigation of herb-drug interaction between S. chinensis and PMZ. The potential pharmacokinetic herb-drug interaction of PMZ- and schisandrin-containing preparations should be noted.http://dx.doi.org/10.1155/2019/3497045
spellingShingle Sijia Gao
Xuelin Zhou
Liwei Lang
Honghong Liu
Jianyu Li
Haotian Li
Shizhang Wei
Dan Wang
Zhuo Xu
Huadan Cai
Yanling Zhao
Wenjun Zou
Simultaneous Determination of Schisandrin and Promethazine with Its Metabolite in Rat Plasma by HPLC-MS/MS and Its Application to a Pharmacokinetic Study
International Journal of Analytical Chemistry
title Simultaneous Determination of Schisandrin and Promethazine with Its Metabolite in Rat Plasma by HPLC-MS/MS and Its Application to a Pharmacokinetic Study
title_full Simultaneous Determination of Schisandrin and Promethazine with Its Metabolite in Rat Plasma by HPLC-MS/MS and Its Application to a Pharmacokinetic Study
title_fullStr Simultaneous Determination of Schisandrin and Promethazine with Its Metabolite in Rat Plasma by HPLC-MS/MS and Its Application to a Pharmacokinetic Study
title_full_unstemmed Simultaneous Determination of Schisandrin and Promethazine with Its Metabolite in Rat Plasma by HPLC-MS/MS and Its Application to a Pharmacokinetic Study
title_short Simultaneous Determination of Schisandrin and Promethazine with Its Metabolite in Rat Plasma by HPLC-MS/MS and Its Application to a Pharmacokinetic Study
title_sort simultaneous determination of schisandrin and promethazine with its metabolite in rat plasma by hplc ms ms and its application to a pharmacokinetic study
url http://dx.doi.org/10.1155/2019/3497045
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