RESUMO
AIM: Fexinidazole (FEX) is a nitroimidazole being developed as a new trypanocide treatment for human African trypanosomiasis/sleeping sickness. Its main metabolites, fexinidazole sulfoxide (M1) and fexinidazole sulfone (M2), show the same in vitro pharmacological activity as FEX. METHODS & RESULTS: An LC-MS/MS assay was developed for quantitation of FEX in DBS, collected via finger-prick from healthy subjects. The DBS assay was specific, accurate and reproducible for FEX, M1 and M2 when validated against the current plasma assay. DBS samples were stable for 24 h at 37°C with 95% relative humidity, and 58 weeks desiccated at room temperature. CONCLUSION: DBS finger-prick sampling offers a simple, practical method for determining FEX, M1 and M2 concentrations in clinical studies in Africa.
Assuntos
Análise Química do Sangue/métodos , Cromatografia Líquida de Alta Pressão , Teste em Amostras de Sangue Seco , Nitroimidazóis/sangue , Espectrometria de Massas em Tandem , Tripanossomicidas/sangue , Administração Oral , Análise Química do Sangue/instrumentação , Cromatografia Líquida de Alta Pressão/normas , Teste em Amostras de Sangue Seco/normas , Hematócrito , Hemólise , Humanos , Modelos Lineares , Nitroimidazóis/metabolismo , Nitroimidazóis/normas , Controle de Qualidade , Espectrometria de Massas em Tandem/normas , Temperatura , Fatores de Tempo , Tripanossomicidas/metabolismo , Tripanossomicidas/normasRESUMO
Characterization of glycosaminoglycans poses a challenge for current analytical techniques, as they are highly acidic, polydisperse and heterogeneous compounds. The purpose of this study is the separation and analysis of a partially depolymerized heparin-like glycosaminoglycan by on-line ion-pairing reversed-phase high-performance liquid chromatography/electrospray mass spectrometry. The gas-phase behavior of two synthesized glycosaminoglycans has been investigated. Dibutylamine was found to be the best suited ion-pairing reagents for mass spectrometry analysis. The optimized ion-pairing conditions provide reproducible and easily interpretable electrospray mass spectra in both negative and positive ESI modes. The glycosaminoglycans are detected as a non-covalent complex with amines. In fact, the observed ionic species and their gas-phase dissociation under CID conditions revealed the presence of salt bridge interactions in the gas phase.