UPLC-MS/MS for simultaneous quantification of vortioxetine and its metabolite Lu AA34443 in rat plasma and its application to drug interactions
Vortioxetine is currently used as the first-line therapy drug for major depressive disorder (MDD). In the present study, we aimed to develop and fully validate an ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method for the simultaneous quantification of vortioxetine...
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| Format: | Article |
| Language: | English |
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Elsevier
2020-11-01
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| Series: | Arabian Journal of Chemistry |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S1878535220303907 |
| _version_ | 1818301017110872064 |
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| author | Er-Min Gu Yuanyuan Shao Wei-Feng Xu Lei Ye Ren-ai Xu |
| author_facet | Er-Min Gu Yuanyuan Shao Wei-Feng Xu Lei Ye Ren-ai Xu |
| author_sort | Er-Min Gu |
| collection | DOAJ |
| description | Vortioxetine is currently used as the first-line therapy drug for major depressive disorder (MDD). In the present study, we aimed to develop and fully validate an ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method for the simultaneous quantification of vortioxetine and its major metabolite Lu AA34443 in plasma and to investigate the effects of dronedarone and amiodarone on vortioxetine metabolism in rats. After protein precipitation with acetonitrile, the separation of vortioxetine, Lu AA34443 and duloxetine (internal standard, IS) were finished on an Acquity BEH C18 (2.1 mm × 50 mm, 1.7 μm) column and their detections were conducted by a Xevo TQ-S triple quadrupole tandem mass spectrometer in the positive ion mode. The assay displayed excellent linearity in the range of 0.5–50 ng/mL for vortioxetine, and 5–1000 ng/mL for Lu AA34443. The results of this method exhibited that the precision, accuracy, matrix effect, recovery, and stability of vortioxetine and Lu AA34443 met all requirements for the quantitation in plasma samples. The validated assay was further successfully employed to study the effects of dronedarone (80 mg/kg) and amiodarone (60 mg/kg) on vortioxetine metabolism in rats. The results showed that dronedarone and amiodarone could increase the concentration of vortioxetine and have inhibitory effect on vortioxetine metabolism. Thus, vortioxetine dose interruption or reduction may be considered. |
| first_indexed | 2024-12-13T05:16:19Z |
| format | Article |
| id | doaj.art-fddc2fef97924e6699e79738cc0656ae |
| institution | Directory Open Access Journal |
| issn | 1878-5352 |
| language | English |
| last_indexed | 2024-12-13T05:16:19Z |
| publishDate | 2020-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Arabian Journal of Chemistry |
| spelling | doaj.art-fddc2fef97924e6699e79738cc0656ae2022-12-21T23:58:25ZengElsevierArabian Journal of Chemistry1878-53522020-11-01131182188225UPLC-MS/MS for simultaneous quantification of vortioxetine and its metabolite Lu AA34443 in rat plasma and its application to drug interactionsEr-Min Gu0Yuanyuan Shao1Wei-Feng Xu2Lei Ye3Ren-ai Xu4The First People’s Hospital of Jiashan, Jiaxing, Zhejiang 314100, ChinaThe First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, ChinaThe First People’s Hospital of Jiashan, Jiaxing, Zhejiang 314100, ChinaThe First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, China; Corresponding authors.The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, China; Corresponding authors.Vortioxetine is currently used as the first-line therapy drug for major depressive disorder (MDD). In the present study, we aimed to develop and fully validate an ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method for the simultaneous quantification of vortioxetine and its major metabolite Lu AA34443 in plasma and to investigate the effects of dronedarone and amiodarone on vortioxetine metabolism in rats. After protein precipitation with acetonitrile, the separation of vortioxetine, Lu AA34443 and duloxetine (internal standard, IS) were finished on an Acquity BEH C18 (2.1 mm × 50 mm, 1.7 μm) column and their detections were conducted by a Xevo TQ-S triple quadrupole tandem mass spectrometer in the positive ion mode. The assay displayed excellent linearity in the range of 0.5–50 ng/mL for vortioxetine, and 5–1000 ng/mL for Lu AA34443. The results of this method exhibited that the precision, accuracy, matrix effect, recovery, and stability of vortioxetine and Lu AA34443 met all requirements for the quantitation in plasma samples. The validated assay was further successfully employed to study the effects of dronedarone (80 mg/kg) and amiodarone (60 mg/kg) on vortioxetine metabolism in rats. The results showed that dronedarone and amiodarone could increase the concentration of vortioxetine and have inhibitory effect on vortioxetine metabolism. Thus, vortioxetine dose interruption or reduction may be considered.http://www.sciencedirect.com/science/article/pii/S1878535220303907VortioxetineLu AA34443Pharmacokinetic interactionUPLC-MS/MSInhibitory effect |
| spellingShingle | Er-Min Gu Yuanyuan Shao Wei-Feng Xu Lei Ye Ren-ai Xu UPLC-MS/MS for simultaneous quantification of vortioxetine and its metabolite Lu AA34443 in rat plasma and its application to drug interactions Arabian Journal of Chemistry Vortioxetine Lu AA34443 Pharmacokinetic interaction UPLC-MS/MS Inhibitory effect |
| title | UPLC-MS/MS for simultaneous quantification of vortioxetine and its metabolite Lu AA34443 in rat plasma and its application to drug interactions |
| title_full | UPLC-MS/MS for simultaneous quantification of vortioxetine and its metabolite Lu AA34443 in rat plasma and its application to drug interactions |
| title_fullStr | UPLC-MS/MS for simultaneous quantification of vortioxetine and its metabolite Lu AA34443 in rat plasma and its application to drug interactions |
| title_full_unstemmed | UPLC-MS/MS for simultaneous quantification of vortioxetine and its metabolite Lu AA34443 in rat plasma and its application to drug interactions |
| title_short | UPLC-MS/MS for simultaneous quantification of vortioxetine and its metabolite Lu AA34443 in rat plasma and its application to drug interactions |
| title_sort | uplc ms ms for simultaneous quantification of vortioxetine and its metabolite lu aa34443 in rat plasma and its application to drug interactions |
| topic | Vortioxetine Lu AA34443 Pharmacokinetic interaction UPLC-MS/MS Inhibitory effect |
| url | http://www.sciencedirect.com/science/article/pii/S1878535220303907 |
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