Determination of Mifepristone (RU-486) and Its Metabolites in Maternal Blood Sample after Pharmacological Abortion

• Published in: Molecules (Basel, Switzerland) Switzerland), 2022-11, Vol.27 (21), p.7605
• Main Authors: Szpot, Paweł, Wachełko, Olga, Jurek, Tomasz, Zawadzki, Marcin
• Format: Article
• Language: English
• Subjects: Abortion; Abortion, Induced - methods; Analysis; Autopsies; Bioavailability; Blood; Chromatography; Developing countries; Female; Fetuses; Forensic science; forensic toxicological investigations; Gas flow; Humans; Internet; LDCs; Mass spectrometry; Metabolic pathways; Metabolism; Metabolites; Mifepristone; Miscarriage; Pharmacokinetics; pharmacological abortion; Pharmacology; Physiological aspects; Pregnancy; RU-486 metabolism; Scientific imaging; Tandem Mass Spectrometry; Toxicology; UHPLC-QqQ-MS/MS; Womens health
• ISSN: 1420-3049; 1420-3049
• 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).