Development and validation of a stability-indicating method, structural elucidation of new degradation products from misoprostol by LC-MS time-of-flight, and an ex vivo study of vaginal permeation.

Autor: da Silva JWV; Pharmaceutical and Cosmetic Development Center (NUDFAC), Federal University of Pernambuco (UFPE), Recife, Brazil., Duarte ML; Pharmaceutical and Cosmetic Development Center (NUDFAC), Federal University of Pernambuco (UFPE), Recife, Brazil., Ribeiro JI; Department of Pharmaceutical Sciences, Center for Quality Control of Medicines and Related Products (NCQMC), Federal University of Pernambuco (UFPE), Recife, Brazil., Kishishita J; Pharmaceutical and Cosmetic Development Center (NUDFAC), Federal University of Pernambuco (UFPE), Recife, Brazil., Souza ATM; Pharmaceutical and Cosmetic Development Center (NUDFAC), Federal University of Pernambuco (UFPE), Recife, Brazil., Leal LB; Pharmaceutical and Cosmetic Development Center (NUDFAC), Federal University of Pernambuco (UFPE), Recife, Brazil., de Castro WV; Graduate Program Pharmaceutical Sciences, Federal University of São João del-Rei, Divinópolis, Minas Gerais, Brazil., de Santana DP; Pharmaceutical and Cosmetic Development Center (NUDFAC), Federal University of Pernambuco (UFPE), Recife, Brazil., Bedor DCG; Pharmaceutical and Cosmetic Development Center (NUDFAC), Federal University of Pernambuco (UFPE), Recife, Brazil.
Jazyk: angličtina
Zdroj: Biomedical chromatography : BMC [Biomed Chromatogr] 2024 Aug; Vol. 38 (8), pp. e5897. Date of Electronic Publication: 2024 May 29.
DOI: 10.1002/bmc.5897
Abstrakt: Misoprostol (MSP) is commonly prescribed in obstetrics and gynecology clinical practice for labor induction, cervical ripening, first-trimester pregnancy termination, and the treatment of postpartum hemorrhage. Furthermore, there is a lack of comprehensive discussion evaluating how different commercially available formulations influence the overall efficacy of MSP, even though reports indicate issues with the quality of these formulations, particularly regarding stability and vaginal absorption processes. This study investigates the stability of MSP under acidic conditions and its in vitro permeation using swine vaginal mucosa. A forced degradation study was conducted using 0.2 M HCl, and a high-efficiency LC method was developed. Three degradation products were identified and characterized using electrospray ionization-high-resolution quadrupole-time-of-flight-MS, with respective m/z values of 391.2508, 405.2705, and 387.2259, respectively. These results suggest that the degradation mechanism involves dehydration of the β-hydroxy ketone moiety, followed by isomerization to its most resonance-stable form and de-esterification. Finally, the in vitro permeation study revealed that the esterified form of MSP was unable to permeate the mucosa and required prior degradation for any component to be detected in the receptor fluid.
(© 2024 John Wiley & Sons Ltd.)
Databáze: MEDLINE
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