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

Autor(es)

de Oliveira Filgueira, Gabriela Campos ^[1] ; Pinto Rodrigues, Grazielle de Fatima ^[1] ; de Lima Benzi, Jhohann Richard ^[2] ; Balthazar Nardotto, Glauco Henrique ^[2] ; Marques, Maria Paula ^[2] ; Lanchote, Vera Lucia ^[2] ; Cavalli, Ricardo Carvalho ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Gynecol & Obstet, Ribeirao Preto, SP - Brazil

^[2] Univ Sao Paulo, Sch Pharmaceut Sci Ribeirao Preto, Dept Clin Anal Food Sci & Toxicol, Ribeirao Preto, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Journal of Pharmaceutical and Biomedical Analysis; v. 202, AUG 5 2021.
• Citações Web of Science: 0

Resumo

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 mu g 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, 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 mu g 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. (C) 2021 Published by Elsevier B.V. (AU)

• Processo FAPESP: 14/19822-3 - Efeitos da obesidade materna na farmacocinética do misoprostol vaginal durante a indução do trabalho de parto
• Beneficiário: Ricardo de Carvalho Cavalli
• Modalidade de apoio: Auxílio à Pesquisa - Regular