Determination of misoprostol acid in plasma samples by UPLC-MS/MS with application in a maternal-fetal pharmacokinetic study following a low misoprostol dose vaginally to induce labor.

Autor: de Oliveira Filgueira GC; Department of Gynecology and Obstetrics, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, SP, Brazil., de Fátima Pinto Rodrigues G; Department of Gynecology and Obstetrics, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, SP, Brazil., Benzi JRL; Department of Clinical Analysis, Food Science and Toxicology, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil., Nardotto GHB; Department of Clinical Analysis, Food Science and Toxicology, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil., Marques MP; Department of Clinical Analysis, Food Science and Toxicology, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil., Lanchote VL; Department of Clinical Analysis, Food Science and Toxicology, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil., Cavalli RC; Department of Gynecology and Obstetrics, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, SP, Brazil. Electronic address: rcavalli@fmrp.usp.br.
Jazyk: angličtina
Zdroj: Journal of pharmaceutical and biomedical analysis [J Pharm Biomed Anal] 2021 Aug 05; Vol. 202, pp. 114138. Date of Electronic Publication: 2021 May 11.
DOI: 10.1016/j.jpba.2021.114138
Abstrakt: Misoprostol is a prostaglandin E1 synthetic analogous used for elective interruptions of early pregnancy, treatment of incomplete abortion, postpartum hemorrhage and induction of full-term labor. Its a lipophilic drug, passing by extensive and rapid pre-systemic metabolism into the active metabolite, misoprostol acid (MA). The objective of this study was to develop and validate a highly sensitive method for MA determination in plasma using UPLC-MSMS, with application in a study of maternal-fetal pharmacokinetics in healthy parturients women (n = 10) after administration of 25 μg misoprostol vaginally. The method presented linearity of 2-10 pg/mL and acceptable precision, accuracy, plasma and solution stability. The parturients women presented median (interquartile range) values of AUC 0-6 of 68.0 (40.8-84.7) pg.h/mL, C max of 21.9 (11.9-30.1) pg/mL and T max of 2.25 (0.69-5.00) h. The placental transfer of MA was assessed from the umbilical vein/maternal blood ratios of 1.40 (0.91-2.13) and intervillous space/maternal blood ratios of 0.49 (0.15-3.41). In conclusion, this method presented high sensitivity, being able to quantify MA in plasma samples following a low 25 μg misoprostol administered vaginally aimed to induce labor in parturients women. Additionally, this is the first description of the placental transfer of MA after a vaginal administration of misoprostol.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2021. Published by Elsevier B.V.)
Databáze: MEDLINE