Pharmacokinetics of H002, a novel S1PRmodulator, and its metabolites in rat blood using liquid chromatography-tandem mass spectrometry.
- Author:
Jiaqi MI
1
;
Manman ZHAO
1
;
Shu YANG
1
;
Shuang YANG
1
;
Jing JIN
1
;
Xiaojian WANG
1
;
Qiong XIAO
1
;
Jinping HU
1
;
Yan LI
1
Author Information
1. Department of Drug Metabolism, Beijing Key Laboratory of Non-Clinical Drug Metabolism and PK/PD study, Key Laboratory of Active Substances Discovery and Drug Ability Evaluation, State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China.
- Publication Type:Journal Article
- Keywords:
LC–MS/MS;
Metabolite;
Periphery blood lymphocyte;
Pharmacokinetics;
S1P analogue;
S1P receptor;
S1PR1 modulator;
Sphingosine-1-phosphate
- From:
Acta Pharmaceutica Sinica B
2016;6(6):576-583
- CountryChina
- Language:English
-
Abstract:
A rapid and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for the simultaneous determination of H002 and its phosphorylated metabolite, H002-P and hydroxylated metabolite H002-M, in rat blood. H001, an analogue of H002, was used as the internal standard. Blood samples were prepared by simple protein precipitation. The analytes and internal standard were separated on a Zorbax SB-C18 column with a gradient mobile phase consisting of methanol and water containing 0.1% formic acid at a flow rate of 0.2 mL/min with an operating temperature of 20 °C. The detection was performed on a triple quadrupole tandem mass spectrometer with positive electrospray ionization in multiple-reaction monitoring mode. Linear detection responses were obtained from 0.2-100 ng/mL for H002 and H002-M, while 0.5-100 ng/mL for H002-P. The intra- and inter-day precision (RSD%) was within 11.76%, with the accuracy (RE%) ranging from -9.84% to 9.12%. The analytes were shown to be stable during sample storage, preparation and analytic procedures. The method was applied to determine the pharmacokinetics of H002 in rats, and a preliminary study showed that the pharmacokinetics of H002 correlated with its biological effect on peripheral blood lymphocytes.
