A high-performance liquid chromatography method for the quantification of cysmethynil, an inhibitor of isoprenylcysteine carboxylmethyl transferase, in mouse plasma

Abstract

Cysmethynil, a newly identified small molecule inhibitor of isoprenylcysteine carboxylmethyl transferase (Icmt) is involved in the post-translational modification of CaaX proteins. Cysmethynil causes cell death in many human cancer cells in vitro, and inhibits tumor growth in the xenograft mouse model in vivo. A HPLC method for the quantification of cysmethynil in mouse plasma was developed and validated. The lower limit of quantification of this method was 0.01 μg/ml. Inter- and intra-day variability ranged from 0.38-8.5% and accuracy was between 86% and 98%. This sensitive method was used to quantify cysmethynil in plasma of mice after intraperitoneal dosing for preliminary pharmacokinetic studies. © 2009 Elsevier B.V. All rights reserved.