Résumé
A simple, sensitive and reliable method was developed for simultaneous quantification of IMM-H007 and its major active metabolites-M1 and MP in the blood of rhesus monkey using HPLC-MS/MS analysis. The analytes and internal standard (IS) WS070119 were separated using a Capcell PAK ADME Column (2.1 mm×100 mm, 3 μm, Shiseido, Japan) with a gradient mobile phase of methanol/water containing 0.1% formic acid. The detection was performed in positive selected reaction monitoring (SRM) mode with electrospray ionization (ESI) source. Satisfactory linearity was obtained while the inter-and intra-assay precision and accuracy differences were no more than 15% with high recovery and good stability for the quantification, indicating the present method was specific, accurate and reliable. The method was successfully applied to the pharmacokinetic study of IMM-H007 in rhesus monkey. After single oral administration of IMM-H007 (70, 210, 630 mg·kg-1), M1 and MP were detected in blood, while the concentration of IMM-H007 was much lower than its metabolites. The active metabolite MP with linear kinetics had a higher exposure than other analytes in vivo. The results provide an useful and reliable model for pharmacological and toxicological studies of IMM-H007 as well as its clinical application.