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 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.
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