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Pharmacokinetic and metabolic studies of Vortioxetine in rats using ultra high performance liquid chromatography with tandem mass spectrometry
Author(s) -
Guan Su,
Zou Yake,
Jia Bingjie,
Wu Lvying,
Yang Zhicheng,
Yuan Fang,
Zhang Lei
Publication year - 2018
Publication title -
journal of separation science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.72
H-Index - 102
eISSN - 1615-9314
pISSN - 1615-9306
DOI - 10.1002/jssc.201800607
Subject(s) - vortioxetine , chemistry , chromatography , pharmacokinetics , tandem mass spectrometry , mass spectrometry , metabolite , high performance liquid chromatography , in vivo , liquid chromatography–mass spectrometry , pharmacology , antidepressant , biochemistry , medicine , microbiology and biotechnology , biology , hippocampus
Vortioxetine is a multimodal antidepressant that has been recently utilized globally. Vortioxetine hemi‐hydrochloride is a novel salt that was previously reported in our research. However, the pharmacokinetics of this salt and the metabolites of Vortioxetine in vivo remain unknown. In this study, the pharmacokinetics of the Vortioxetine hemi‐hydrochloride salt is explored in rats through a newly developed ultra‐performance liquid chromatography with tandem mass spectrometry method. In addition, ultra‐performance liquid chromatography coupled with quadrupole time of flight mass spectrometry was used to identify the metabolites of Vortioxetine in vivo. The results demonstrate that after a single, 3 mg/kg oral dose, the maximum concentration for the Vortioxetine hemi‐hydrochloride salt is 14.63 ± 4.00 ng/mL, and is attained in 1.00∼4.00 h. The area under the plasma concentration‐time curve from time 0 to 24 h is 67.30 ± 23.78 ng·h·mL −1 . Additionally, 29 metabolites were identified after the oral administration of 10 mg/kg, including 17 metabolites in the plasma, nine in the urine, and 12 in the feces. Eleven metabolites were novel. The major metabolic pathways include methylation, hydroxylation, oxidation, and glucuronidation. In conclusion, this study provides insight for further development of the Vortioxetine hemi‐hydrochloride salt.