Castoldi D, Oggioni A, Renoldi M I, Ratti E, Di Giovine S, Bernareggi A
Boehringer Mannheim Italia S.p.A., Monza.
J Chromatogr B Biomed Appl. 1994 May 13;655(2):243-52. doi: 10.1016/0378-4347(94)00066-2.
Moguisteine is a novel peripheral non-narcotic antitussive agent. Pharmacokinetic studies in animal and in man showed that no unchanged drug is present in plasma, urine and faeces after oral administration. The main active metabolite, M1, is the free carboxylic acid of moguisteine, which maintains a stereogenic centre and consists of R(+)-M1 and S(-)-M1 enantiomers. M1 is partly metabolized to M2, its sulfoxidation derivative. A conventional HPLC method is described for the simultaneous determination of M1 and M2 in human plasma and urine after administration of therapeutic moguisteine doses. Plasma samples, previously acidified with phosphoric acid, are extracted with dichloromethane; urine samples are analyzed after appropriate dilution with methanol. Chromatography is performed using a Lichrosorb RP2 column and a linear gradient. M1 enantiomers can be determined in plasma extracts and urine samples by a chiral HPLC method using a beta-cyclodextrin column. The analytical characteristics of both HPLC procedures proved to be adequate to analyze samples of subjects treated with therapeutic doses of moguisteine during clinical pharmacokinetic studies.
莫吉司坦是一种新型外周性非麻醉性镇咳药。在动物和人体中进行的药代动力学研究表明，口服给药后，血浆、尿液和粪便中不存在未变化的药物。主要活性代谢物M1是莫吉司坦的游离羧酸，它保持一个手性中心，由R(+)-M1和S(-)-M1对映体组成。M1部分代谢为其亚砜氧化衍生物M2。本文描述了一种常规高效液相色谱法，用于在给予治疗剂量的莫吉司坦后同时测定人血浆和尿液中的M1和M2。预先用磷酸酸化的血浆样品用二氯甲烷萃取；尿液样品用甲醇适当稀释后进行分析。使用Lichrosorb RP2柱和线性梯度进行色谱分析。M1对映体可以通过使用β-环糊精柱的手性高效液相色谱法在血浆提取物和尿液样品中测定。在临床药代动力学研究中，两种高效液相色谱方法的分析特性均证明足以分析接受治疗剂量莫吉司坦治疗的受试者的样品。
