A simple HPLC-UV method for the simultaneous quantification of gefitinib and erlotinib in human plasma

作者:Faivre Lionel; Gomo Charline; Mir Olivier; Taieb Fabrice; Schoemann Thomas Audrey; Ropert Stanislas; Vidal Michel; Dusser Daniel; Dauphin Alain; Goldwasser Francois; Blanchet Benoit*
来源:Journal of Chromatography B-Analytical Technologies in the Biomedical and Life Sciences, 2011, 879(23): 2345-2350.
DOI:10.1016/j.jchromb.2011.06.026

摘要

Gefitinib and erlotinib are two oral tyrosine kinase inhibitors (TKI) approved for the treatment of advanced non-small cell lung cancer (NSCLC). Published methods for simultaneous analysis of erlotinib and gefitinib in plasma are exclusively based on mass spectrometry. The purpose of this study was to develop a simple and sensitive HPLC-UV method to simultaneously quantify these two TKI in plasma. Following liquid-liquid extraction, gefitinib, erlotinib and sorafenib (internal standard), were separated with gradient elution (on a C8+ Satisfaction (R) using a mobile phase of acetonitrile/20 mM ammonium acetate pH 4.5). Samples were eluted at a flow rate of 0.4 ml/min throughout the 15-min run. Dual UV wavelength mode was used, with gefitinib and erlotinib monitored at 331 nm, and sorafenib at 249 nm. The calibration was linear in the range 20-1000 ng/ml and 80-4000 ng/ml for gefitinib and erlotinib, respectively. Inter- and intra-clay imprecision were less than 7.2% and 7.6% for gefitinib and erlotinib, respectively. This analytical method was successfully applied to assess the steady state plasma exposure to these TKI in NSCLC patients. This simple, sensitive, accurate and cost-effective method can be used in routine clinical practice to monitor gefitinib or erlotinib concentrations in plasma from NSCLC patients.

  • 出版日期2011-8-1