Determination of a novel dipeptidyl peptidase IV inhibitor in monkey plasma by HPLC-MS/MS and its application in a pharmacokinetics study.
A lot of attention has been given to novel diabetes treatment, which is used to replace injectable insulin. A novel dipeptidyl peptidase IV inhibitor (HWH-10d) for treating type 2 diabetes was previously determined to have comparable efficacy to the marketed drug (alogliptin) in ICR male mice. Therefore, a sensitive and rapid liquid chromatography-tandem mass spectrometric method was developed and validated for the further evaluation of HWH-10d in monkey. The analytes were extracted through a liquid-liquid extraction with ethyl acetate. The linear detection range for HWH-10d in monkey plasma was from 0.5 to 2000 ng/mL with the lower limit of quantification of 0.5 ng/mL. The relative standard deviation was measured to be less than 10.4% for determination of inter- and intra-day precisions, and the relative error was determined to be within ±7.2% for all accuracy measurements. The simple and rapid LC-MS/MS method for HWH-10d in monkey plasma could be used for the pharmacokinetics studies of HWH-10d in monkeys. The oral bioavailability of HWH-10d in monkeys is 57.8%.
School of Bioscience & Bioengineering, South China University of Technology, Guangzhou 510640, PR China.
Jifeng
J
Deng
Zhongshan PharmaSS Corporation, Zhongshan 528437, PR China.
Jiayin
J
Guo
School of Bioscience & Bioengineering, South China University of Technology, Guangzhou 510640, PR China.
Renke
R
Dai
Guangzhou Institute of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510663, PR China.
Guicheng
G
Zhang
The First Affiliated Hospital of Guangzhou Medical University, 151 Yanjiang Road, Guangzhou 510120, PR China. Electronic address: xie_hui126@163.com.
Hui
H
Xie
D000818:Animals; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000097:blood* / Q000493:pharmacokinetics*; D005260:Female; D008252:Macaca fascicularis; D008297:Male; D053719:Tandem Mass Spectrometry / Q000379:methods*
D054873:Dipeptidyl-Peptidase IV Inhibitors
DPP-IV inhibitor; HWH-10d; LC–MS/MS; Pharmacokinetics; Type 2 diabetes