Simultaneous determination of amiodarone, dronedarone, and their principal metabolites in SD rat plasma by UPLC-MS/MS and its application in pharmacokinetics
The purpose of the experiment was mainly to establish and verify a precise and straightforward ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) approach for simultaneously analyzing the concentration levels of amiodarone, dronedarone, and their metabolites (desethylamiod...
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Elsevier
2021-08-01
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Series: | Arabian Journal of Chemistry |
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Online Access: | http://www.sciencedirect.com/science/article/pii/S1878535221003154 |
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author | Ying Zhang Mengxiao Zhu Saili Xie Xuemei Ye Xuegu Xu |
author_facet | Ying Zhang Mengxiao Zhu Saili Xie Xuemei Ye Xuegu Xu |
author_sort | Ying Zhang |
collection | DOAJ |
description | The purpose of the experiment was mainly to establish and verify a precise and straightforward ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) approach for simultaneously analyzing the concentration levels of amiodarone, dronedarone, and their metabolites (desethylamiodarone and desbutyldronedarone) in the plasma of Sprague-Dawley (SD) rats and to investigate the pharmacokinetics of all analytes in SD rats. After rapid protein precipitation by using acetonitrile, we accomplished the chromatographic separation of amiodarone, desethylamiodarone, dronedarone, desbutyldronedarone and ivabradine (internal standard, IS) by using Acquity BEH C18 column and detected through a mass spectrometer with Xevo TQ-S triple quadrupole tandem, choosing the positive ion mode. The approach showed wonderful linearity, and the range of calibration curve for amiodarone was 1–200 ng/mL, desethylamiodarone was 0.1–20 ng/mL, dronedarone was 0.5–100 ng/mL, and desbutyldronedarone was 0.25–50 ng/mL, respectively. For lower limit of quantification (LLOQ), the current method of UPLC-MS/MS can achieve values of 1.0 ng/mL for amiodarone, 0.1 ng/mL for desethylamiodarone, 0.5 ng/mL for dronedarone, and 0.25 ng/mL for desbutyldronedarone, respectively. The accuracy of intra-day and inter-day of all analytes was between −14.8% to 10.9%, while the precision was ≤ 13.3%. For each substance, the recovery rate was > 82.1%, besides, obvious matrix effect was not found. In all conditions, the stability of all analytes was comfirmed to the plasma sample quantification. In addition, the method of UPLC-MS/MS we developed could also be applied to measure the pharmacokinetic characteristics including amiodarone, desethylamiodarone, dronedarone, and desbutyldronedarone in the plasma of SD rats. |
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spelling | doaj.art-0b00a5d81a774c8da02c9082d28ff12e2022-12-21T18:51:18ZengElsevierArabian Journal of Chemistry1878-53522021-08-01148103300Simultaneous determination of amiodarone, dronedarone, and their principal metabolites in SD rat plasma by UPLC-MS/MS and its application in pharmacokineticsYing Zhang0Mengxiao Zhu1Saili Xie2Xuemei Ye3Xuegu Xu4Department of Pharmacy, HwaMei Hospital, University of Chinese Academy of Sciences (Ningbo No.2 Hospital), 315010 Ningbo, Zhejiang, China; Ningbo Institute of Life and Health Industry, University of Chinese Academy of Sciences, 315010 Ningbo, Zhejiang, ChinaDaping Hospital, Army Medical University, 401120 Chongqing, Chongqing, ChinaThe First Affiliated Hospital of Wenzhou Medical University, 325000 Wenzhou, Zhejiang, ChinaThe First Affiliated Hospital of Wenzhou Medical University, 325000 Wenzhou, Zhejiang, China; Corresponding authors.The Eye Hospital of Wenzhou Medical University, 325000 Wenzhou, Zhejiang, China; Corresponding authors.The purpose of the experiment was mainly to establish and verify a precise and straightforward ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) approach for simultaneously analyzing the concentration levels of amiodarone, dronedarone, and their metabolites (desethylamiodarone and desbutyldronedarone) in the plasma of Sprague-Dawley (SD) rats and to investigate the pharmacokinetics of all analytes in SD rats. After rapid protein precipitation by using acetonitrile, we accomplished the chromatographic separation of amiodarone, desethylamiodarone, dronedarone, desbutyldronedarone and ivabradine (internal standard, IS) by using Acquity BEH C18 column and detected through a mass spectrometer with Xevo TQ-S triple quadrupole tandem, choosing the positive ion mode. The approach showed wonderful linearity, and the range of calibration curve for amiodarone was 1–200 ng/mL, desethylamiodarone was 0.1–20 ng/mL, dronedarone was 0.5–100 ng/mL, and desbutyldronedarone was 0.25–50 ng/mL, respectively. For lower limit of quantification (LLOQ), the current method of UPLC-MS/MS can achieve values of 1.0 ng/mL for amiodarone, 0.1 ng/mL for desethylamiodarone, 0.5 ng/mL for dronedarone, and 0.25 ng/mL for desbutyldronedarone, respectively. The accuracy of intra-day and inter-day of all analytes was between −14.8% to 10.9%, while the precision was ≤ 13.3%. For each substance, the recovery rate was > 82.1%, besides, obvious matrix effect was not found. In all conditions, the stability of all analytes was comfirmed to the plasma sample quantification. In addition, the method of UPLC-MS/MS we developed could also be applied to measure the pharmacokinetic characteristics including amiodarone, desethylamiodarone, dronedarone, and desbutyldronedarone in the plasma of SD rats.http://www.sciencedirect.com/science/article/pii/S1878535221003154AmiodaroneDronedaronePharmacokineticsUPLC-MS/MSRat plasma |
spellingShingle | Ying Zhang Mengxiao Zhu Saili Xie Xuemei Ye Xuegu Xu Simultaneous determination of amiodarone, dronedarone, and their principal metabolites in SD rat plasma by UPLC-MS/MS and its application in pharmacokinetics Arabian Journal of Chemistry Amiodarone Dronedarone Pharmacokinetics UPLC-MS/MS Rat plasma |
title | Simultaneous determination of amiodarone, dronedarone, and their principal metabolites in SD rat plasma by UPLC-MS/MS and its application in pharmacokinetics |
title_full | Simultaneous determination of amiodarone, dronedarone, and their principal metabolites in SD rat plasma by UPLC-MS/MS and its application in pharmacokinetics |
title_fullStr | Simultaneous determination of amiodarone, dronedarone, and their principal metabolites in SD rat plasma by UPLC-MS/MS and its application in pharmacokinetics |
title_full_unstemmed | Simultaneous determination of amiodarone, dronedarone, and their principal metabolites in SD rat plasma by UPLC-MS/MS and its application in pharmacokinetics |
title_short | Simultaneous determination of amiodarone, dronedarone, and their principal metabolites in SD rat plasma by UPLC-MS/MS and its application in pharmacokinetics |
title_sort | simultaneous determination of amiodarone dronedarone and their principal metabolites in sd rat plasma by uplc ms ms and its application in pharmacokinetics |
topic | Amiodarone Dronedarone Pharmacokinetics UPLC-MS/MS Rat plasma |
url | http://www.sciencedirect.com/science/article/pii/S1878535221003154 |
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