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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.

作者信息

de Oliveira Filgueira Gabriela Campos, de Fátima Pinto Rodrigues Grazielle, Benzi Jhohann Richard de Lima, Nardotto Glauco Henrique Balthazar, Marques Maria Paula, Lanchote Vera Lucia, Cavalli Ricardo Carvalho

机构信息

Department of Gynecology and Obstetrics, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, SP, Brazil.

Department of Clinical Analysis, Food Science and Toxicology, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil.

出版信息

J Pharm Biomed Anal. 2021 Aug 5;202:114138. doi: 10.1016/j.jpba.2021.114138. Epub 2021 May 11.

DOI:10.1016/j.jpba.2021.114138
PMID:34022668
Abstract

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 of 68.0 (40.8-84.7) pg.h/mL, C of 21.9 (11.9-30.1) pg/mL and T 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.

摘要

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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.
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