Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Medicine, Pharmacy Science and Technology of Târgu Mureş, Târgu Mureş, Romania.
Department of Cell Biology and Microbiology, Faculty of Pharmacy, University of Medicine, Pharmacy, Science and Technology of Târgu Mureș, Târgu Mureş, Romania.
Biomed Chromatogr. 2021 Jan;35(1):e4874. doi: 10.1002/bmc.4874. Epub 2020 Jun 1.
Venlafaxine (VFX) is a serotonin and norepinephrine reuptake inhibitor chiral drug used in therapy as an antidepressant in the form of a racemate consisting of R- and S-VFX. The two enantiomers of VFX exhibit different pharmacological activities: R-VFX inhibits both norepinephrine and serotonin synaptic reuptake, whereas S-VFX inhibits only the serotonin one. R- and S-VFX are metabolized in the liver to the respective R- and S-O-desmethylvenlafaxine (ODVFX), R- and S-N-desmethylvenlafaxine (NDVFX), and R- and S-N,O-didesmethylvenlafaxine (NODVFX). The pharmacological profile of ODVFX is close to that of VFX, whereas the other two chiral metabolites (NDVFX and NODVFX) have lower affinity for the receptor sites. The pharmacokinetics of the VFX enantiomers appear stereoselective, including the metabolism process. In the past 20 years, several studies describing the enantioselective analysis of R- and S-VFX in pharmaceutical formulations and its chiral metabolites in biological matrices were published. These methods encompass liquid chromatography coupled with UV detection, mass spectrometry, or tandem mass spectrometry, and capillary electrophoresis. This paper reviews the published methods used for the determination of the individual enantiomers of VFX and its chiral metabolites in different matrices.
文拉法辛（VFX）是一种 5-羟色胺和去甲肾上腺素再摄取抑制剂的手性药物，以消旋体的形式作为抗抑郁药用于治疗，由 R-和 S-VFX 组成。VFX 的两个对映异构体表现出不同的药理活性：R-VFX 抑制去甲肾上腺素和 5-羟色胺突触再摄取，而 S-VFX 仅抑制 5-羟色胺。R-和 S-VFX 在肝脏中代谢为各自的 R-和 S-O-去甲文拉法辛（ODVFX）、R-和 S-N-去甲文拉法辛（NDVFX）和 R-和 S-N,O-去二甲文拉法辛（NODVFX）。ODVFX 的药理特征与 VFX 接近，而其他两种手性代谢物（NDVFX 和 NODVFX）对受体的亲和力较低。VFX 对映异构体的药代动力学似乎具有立体选择性，包括代谢过程。在过去的 20 年中，描述了几种在药物制剂中对 R-和 S-VFX 及其手性代谢物进行对映体选择性分析的方法，并在生物基质中进行了研究。这些方法包括与紫外检测、质谱或串联质谱和毛细管电泳联用的液相色谱法。本文综述了用于测定不同基质中 VFX 及其手性代谢物单个对映异构体的已发表方法。
