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手性色谱分析技术及对接研究用于盐酸美克洛嗪对映体选择性分离:在兔体内药代动力学研究中的应用。

Bioanalytical chiral chromatographic technique and docking studies for enantioselective separation of meclizine hydrochloride: Application to pharmacokinetic study in rabbits.

机构信息

Department of Pharmaceutical Chemistry, JSS College of Pharmacy, JSS Academy of Higher Education and Research, Mysuru, India.

Department of Pharmacology, JSS College of Pharmacy, JSS Academy of Higher Education and Research, Mysuru, India.

出版信息

Chirality. 2020 Aug;32(8):1091-1106. doi: 10.1002/chir.23241. Epub 2020 Jun 21.

Abstract

Enantiomeric resolution and molecular docking studies of meclizine hydrochloride on polysaccharide-based chiral stationary phase comprising cellulose tris(4-methylbenzoate) chiral selector (150 × 4.6 mm, 3.0 μm) were presented. The mobile phase used was acetonitrile:10mM ammonium bicarbonate (95:05, v/v). The developed technique was used to perform the enantioselective assay of meclizine hydrochloride in its marketed formulation. The elution order of meclizine hydrochloride enantiomers was determined by docking studies. Target compound was extracted from rabbit plasma using protein precipitation technique, followed by development of bioanalytical chiral separation method using the same matrix. Application of the method to determine pharmacokinetic parameters of meclizine hydrochloride enantiomers was performed using Phoenix WinNonlin 8.1 software. The results demonstrated stereoselective disposition of meclizine hydrochloride enantiomers in rabbits.

摘要

手性固定相上盐酸美克洛嗪的对映体拆分和分子对接研究 手性固定相由包含纤维素三(4-甲基苯甲酸酯)手性选择体(150×4.6mm,3.0μm)组成。所用的流动相为乙腈:10mM 碳酸氢铵(95:05,v/v)。所开发的技术用于在其市售制剂中进行盐酸美克洛嗪的对映选择性测定。通过对接研究确定了盐酸美克洛嗪对映体的洗脱顺序。采用蛋白沉淀技术从兔血浆中提取目标化合物,然后使用相同基质开发生物分析手性分离方法。使用 Phoenix WinNonlin 8.1 软件进行了测定盐酸美克洛嗪对映体药代动力学参数的方法应用。结果表明,盐酸美克洛嗪对映体在兔体内具有立体选择性分布。

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