Determination of a novel dipeptidyl peptidase IV inhibitor in monkey plasma by HPLC-MS/MS and its application in a pharmacokinetics study

Journal of Pharmaceutical and Biomedical Analysis
Jifeng DengHui Xie

Abstract

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%.

References

May 6, 2004·The Journal of Clinical Endocrinology and Metabolism·Bo AhrénAnja Schweizer
Oct 26, 2005·The International Journal of Biochemistry & Cell Biology·Carolyn F Deacon, Jens J Holst
Mar 14, 2007·Current Topics in Medicinal Chemistry·Nancy A Thornberry, Ann E Weber
Oct 11, 2007·The Journal of Clinical Endocrinology and Metabolism·Andrea MariJames E Foley

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