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.

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 ß-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.

International cooperation and health policy implementation in a post-conflict situation: the case of East Timor / Cooperação internacional e formulação de políticas de saúde em situação pós-conflito: o caso do Timor-Leste

This study centers on relationships among national and international actors in preparation of the first health policy document for East Timor, under the United Nations transitional administration, between 1999 and 2002. International cooperation support for the health system rehabilitation process during the post-conflict period is analyzed as part of reconstruction of the State in parallel with construction of the country's political and institutional framework. Knowledge, ideas, "ways of doing," and induced and accepted practices permeate an interplay of power relationships that condition both national political alliance-building and the architecture of international aid, pointing to input to a discussion of how these mechanisms interact at different conjunctures and times in different negotiating frameworks. .

Dedica-se, aqui, às relações entre diferentes atores na elaboração do primeiro documento de política de saúde para o Timor-Leste, sob a administração transitória das Nações Unidas, de 1999 a 2002. O apoio da cooperação internacional no processo de reabilitação do sistema de saúde no período pós-conflito é analisado como parte da reconstrução do Estado e concomitante à construção do arcabouço político e institucional no país. Conhecimentos, ideias, "modos de fazer" e práticas induzidas e aceitas entremeiam um jogo de relações de poder que condiciona tanto a articulação política nacional quanto a arquitetura da ajuda externa, apontando elementos para a discussão de como esses mecanismos se organizam em conjunturas diferentes de negociação.