Assuntos
Leucemia Mieloide Aguda/terapia , Terapia de Salvação , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Feminino , Transplante de Células-Tronco Hematopoéticas , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Recidiva , Resultado do Tratamento , Adulto JovemRESUMO
How and why the chemical stability of amorphous solid is different from crystalline solid is an important problem. In this study, this problem is addressed by evaluation of the photodegradation of both crystalline and amorphous MK-912 (an alpha-2 adrenoceptor antagonist) according to the photostability tests of the ICH (International Conference on Harmonization) guidelines. Under the ICH conditions, the photodegradation rate of the amorphous MK-912 was approximately 40 times faster than that of the crystalline MK-912. The photodegradation yielded isomeric, oxidative degradates. Three keto-degradates (molecular weight of 14 Da over MK-912) were observed for both forms. But, whereas five alcohol and one N-oxide degradates (molecular weight of 16 Da over MK-912) were observed for the amorphous form, only one alcohol degradate was observed for the crystalline form. Liquid chromatography/mass spectrometry (LC/MS) and LC/MS/MS were applied to identify these low-level photodegradates. A thorough analysis of the MS/MS data of protonated MK-912 was the key to the identification, and the special MS/MS features of the degradates due to the structural modifications from degradations were also important. Following this strategy, the structures of all the photodegradates were proposed. The structural identification of the photodegradates of MK-912 shed light on the different photostabilities between the crystalline and amorphous MK-912.