The stereoselective pharmacokinetics of the desmethyl-phencynonate hydrochloride in beagle dogs

IF 2.8 4区化学 Q2 CHEMISTRY, ANALYTICAL

Chirality Pub Date : 2024-05-15 DOI:10.1002/chir.23669

Jinglai Li, Lan Yin, Yuexin Li, Junying Sun, Xiaoying Wang, Zhenqing Zhang, Shan Xiong

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Abstract

The aim of this study was to investigate the chiral inversion and the stereoselective pharmacokinetic profiles of desmethyl-phencynonate hydrochloride after administration of the single isomer and its racemate to beagle dogs. A liquid chromatography with tandem mass spectrometry (LC–MS/MS) method was established for determination of the stereoisomers on chiral columns in beagle dog plasma, which met all the requirements. The chiral inversion in dogs of the desmethyl-phencynonate hydrochloride were studied after administration of the single isomer or the racemic modification. The stereoselective pharmacokinetic profiles of the desmethyl-phencynonate hydrochloride were studied by assays for simultaneous isomers after administration of the racemic modification. The results showed that the absorption of the Rconfiguration dosed as the single isomer was higher than it dosed as the racemic modification. The AUC_(0-t), AUC_(0-∞), and C_max of the Sconfiguration were much higher than those of Rconfiguration after oral administration of the racemic desmethyl-phencynonate hydrochloride. The chiral inversion of desmethyl-phencynonate isomers could not occur in dogs after administration of the Rconfiguration.

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小猎犬体内去甲基苯丙酮酸盐酸盐的立体选择性药代动力学。

本研究的目的是调查小猎犬服用单异构体及其外消旋体后去甲苯丙酮酸盐酸盐的手性反转和立体选择性药代动力学特征。建立了一种液相色谱-串联质谱（LC-MS/MS）方法，用于测定小猎犬血浆中手性柱上的立体异构体，该方法符合所有要求。研究了狗在服用单一异构体或外消旋修饰物后，去甲苯丙酮酸盐酸盐的手性反转情况。通过测定外消旋修饰物后的同时异构体，研究了去甲基苯骈脲酸盐酸盐的立体选择性药代动力学特征。结果表明，以单一异构体形式给药的 R 构型的吸收率高于以外消旋体形式给药的 R 构型。口服外消旋盐酸去甲苯丙酮后，S构型的AUC（0-t）、AUC（0-∞）和Cmax远高于R构型。狗口服 R 构型后，去甲苯骈酸异构体的手性反转不会发生。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Chirality 医学-分析化学

CiteScore

4.40

自引率

5.00%

发文量

124

审稿时长

1 months

期刊介绍： The main aim of the journal is to publish original contributions of scientific work on the role of chirality in chemistry and biochemistry in respect to biological, chemical, materials, pharmacological, spectroscopic and physical properties. Papers on the chemistry (physiochemical, preparative synthetic, and analytical), physics, pharmacology, clinical pharmacology, toxicology, and other biological aspects of chiral molecules will be published.