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 0.01microg/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.

• Authors: Mei Wang, Yok Moi Khoo, Jin Zhou, Patrick Casey, How Sung Lee
• Journal: Journal of chromatography. B, Analytical technologies in the biomedical and life sciences (J Chromatogr B Analyt Technol Biomed Life Sci) Vol. 877 Issue 5-6 Pg. 553-7 (Feb 15 2009) ISSN: 1570-0232 [Print] Netherlands
• PMID: 19157999 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Enzyme Inhibitors
• Indoles
• cysmethynil
• Protein Methyltransferases

Topics

• Animals
• Chromatography, High Pressure Liquid (methods)
• Drug Stability
• Enzyme Inhibitors (blood, chemistry, metabolism)
• Freezing
• Indoles (blood, chemistry, metabolism)
• Mice
• Mice, Inbred BALB C
• Protein Methyltransferases (antagonists & inhibitors, blood)
• Reproducibility of Results
• Temperature
• Time Factors