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

• Published in: Journal of pharmaceutical and biomedical analysis 2021-08, Vol.202, p.114138-114138, Article 114138
• Main Authors: 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
• Format: Article
• Language: English
• Subjects: Misoprostol; Misoprostol acid; Pharmacokinetics; Placental transfer; Pregnancy; UPLC–MS/MS
• ISSN: 0731-7085; 1873-264X
• DOI: 10.1016/j.jpba.2021.114138

•A validated method for MA analysis in plasma with the lowest LLOQ.•Application in a maternal-fetal pharmacokinetic study.•Method applied in a study of low misoprostol dose of 25 μg administered vaginally.•First report of MA PK following misoprostol 25 μg administered vaginally.•MA showed high placental transfer with accumulation in the fetal compartment. 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 AUC0−6 of 68.0 (40.8–84.7) pg.h/mL, Cmax of 21.9 (11.9–30.1) pg/mL and Tmax 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.