Pharmacokinetics of IMM-H007 after oral administration in Rhesus monkey using HPLC-MS/MS analysis
10.16438/j.0513-4870.2018-0135
- VernacularTitle:HPLC-MS/MS法研究恒河猴口服新型调血脂化合物IMM-H007后的全血药代动力学特征
- Author:
Rui WANG
1
;
Bao-lian WANG
1
;
Yan LI
1
Author Information
1. Beijing Key Laboratory of Non-Clinical Drug Metabolism and PK/PD Study, State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Department of Drug Metabolism, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
- Publication Type:ORIGINAL ARTICLES
- Keywords:
lipid-relating chemical;
rhesus monkey;
pharmacokinetics;
HPLC-MS/MS
- From:
Acta Pharmaceutica Sinica
2018;53(7):1156-1161
- CountryChina
- Language:Chinese
-
Abstract:
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.
