A DBS method for quantitation of the new oral trypanocidal drug fexinidazole and its active metabolites. (October 2016)

• Record Type: Journal Article
• Authors: Filali-Ansary, Aziz; Augé, Cécile; Abgrall, Audrey; Souchaud, Marie; Pellissier, Franck; Mordt, Olaf Valverde; Blesson, Séverine; Sanderink, Ger-Jan
• Is Part Of: Bioanalysis. Volume 8:Number 19(2016)
• Page Start: 2045
• Page End: 2063
• Publication Date: 2016-10
• Subjects: DBS -- fexinidazole -- fexinidazole sulfone -- fexinidazole sulfoxide -- LC–MS/MS -- sleeping sickness; Drugs -- Analysis -- Periodicals; 615.19005
• DOI: 10.4155/bio-2016-0110
• Languages: English
• ISSNs: 1757-6180

Abstract

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.