A DBS method for quantitation of the new oral trypanocidal drug fexinidazole and its active metabolites.
OBJECTIVE
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.


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.


CONCLUSIONS
DBS finger-prick sampling offers a simple, practical method for determining FEX, M1 and M2 concentrations in clinical studies in Africa.
Sanofi R&D, Vitry-Alfortville, France.
Aziz
A
Filali-Ansary
Sanofi-aventis Group, Gentilly, France.
Cécile
C
Augé
Sanofi R&D, Chilly-Mazarin, France.
Audrey
A
Abgrall
Sanofi R&D, Vitry-Alfortville, France.
Marie
M
Souchaud
Sanofi R&D, Montpellier, France.
Franck
F
Pellissier
Drugs for Neglected Diseases initiative (DNDi), Geneva, Switzerland.
Olaf Valverde
OV
Mordt
Drugs for Neglected Diseases initiative (DNDi), Geneva, Switzerland.
Séverine
S
Blesson
Sanofi R&D, Vitry-Alfortville, France.|Sanofi R&D, Chilly-Mazarin, France.
Ger-Jan
GJ
Sanderink
D000284:Administration, Oral; D001774:Blood Chemical Analysis / Q000295:instrumentation / Q000379:methods*; D002851:Chromatography, High Pressure Liquid / Q000592:standards; D059788:Dried Blood Spot Testing / Q000592:standards; D006400:Hematocrit; D006461:Hemolysis; D006801:Humans; D016014:Linear Models; D009593:Nitroimidazoles / Q000097:blood* / Q000378:metabolism / Q000592:standards; D011786:Quality Control; D053719:Tandem Mass Spectrometry / Q000592:standards; D013696:Temperature; D013997:Time Factors; D014344:Trypanocidal Agents / Q000097:blood* / Q000378:metabolism / Q000592:standards
D009593:Nitroimidazoles; D014344:Trypanocidal Agents; C038307:fexinidazole
DBS; LC–MS/MS; fexinidazole; fexinidazole sulfone; fexinidazole sulfoxide; sleeping sickness