Department of Forensic Medicine, Wroclaw Medical University, 4 J. Mikulicza-Radeckiego Street, 50345 Wroclaw, Poland.
Institute of Toxicology Research, 45 Kasztanowa Street, 55093 Borowa, Poland.
Molecules. 2022 Nov 6;27(21):7605. doi: 10.3390/molecules27217605.
The aim of the study was the development and validation of the UHPLC-QqQ-MS/MS method for the determination of mifepristone in human blood as well as the identification and quantification of its metabolites after self-induced pharmacological abortion. The metabolic pathway in humans was proposed after examination of an authentic casework. The fast and simple preanalytical procedure was successfully applied (pH9, tert-butyl-methyl ether). The validation parameters of the method were as follows: limit of quantification: 0.5 ng/mL; coefficients of determination: >0.999 (R2), intra- and inter-day accuracy and precision values did not exceed ± 13.2%. The recovery and matrix effect were in the range of 96.3−114.7% and from −3.0 to 14.7%, respectively. Toxicological analysis of the mother’s blood (collected the day after the pregnancy termination) revealed the presence of five compounds: mifepristone (557.4 ng/mL), N-desmethyl-mifepristone (638.7 ng/mL), 22-OH-mifepristone (176.9 ng/mL), N,N-didesmethyl-mifepristone (144.5 ng/mL) and N-desmethyl-hydroxy-mifepristone (qualitatively). To our knowledge, the study presented in this paper is the first report on the concentrations of mifepristone and its metabolites in maternal blood samples after performing a self-induced abortion. The established UHPLC-QqQ-MS/MS method is suitable for forensic toxicological analysis as well as in terms of clinical toxicology in future investigations (examination of pharmacokinetics, bioavailability and metabolism of RU-486).
本研究旨在开发和验证 UHPLC-QqQ-MS/MS 方法，以测定人血中米非司酮的浓度，并在自我诱导药物流产后鉴定和定量其代谢物。在对一个真实案例进行检查后，提出了人体内的代谢途径。该方法采用了快速简单的预处理程序（pH9，叔丁基-甲基醚）。该方法的验证参数如下：定量下限：0.5ng/mL；决定系数：>0.999（R2），日内和日间准确度和精密度值不超过±13.2%。回收率和基质效应的范围分别为 96.3-114.7%和-3.0-14.7%。对母亲流产后一天采集的血液进行毒理学分析，发现了五种化合物：米非司酮（557.4ng/mL）、N-去甲基米非司酮（638.7ng/mL）、22-羟基米非司酮（176.9ng/mL）、N,N-二去甲基米非司酮（144.5ng/mL）和 N-去甲基羟米非司酮（定性）。据我们所知，本文所报道的研究是首次在自我诱导流产后检测母亲血液中米非司酮及其代谢物浓度的报告。所建立的 UHPLC-QqQ-MS/MS 方法适用于法医毒理学分析以及未来研究中的临床毒理学（检测 RU-486 的药代动力学、生物利用度和代谢）。
