title: A simple HPLC-UV method for the simultaneous quantification of gefitinib and erlotinib in human plasma.
abstract: 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(®) using a mobile phase of acetonitrile/20mM 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-day 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.
authors: Laboratoire de Pharmacologie-Toxicologie, Service de Pharmacie, GH Cochin - Hôtel Dieu - Broca, AP-HP, Paris, France.
authors: Lionel
authors: L
authors: Faivre
authors: Charline
authors: C
authors: Gomo
authors: Olivier
authors: O
authors: Mir
authors: Fabrice
authors: F
authors: Taieb
authors: Audrey
authors: A
authors: Schoemann-Thomas
authors: Stanislas
authors: S
authors: Ropert
authors: Michel
authors: M
authors: Vidal
authors: Daniel
authors: D
authors: Dusser
authors: Alain
authors: A
authors: Dauphin
authors: Francois
authors: F
authors: Goldwasser
authors: Benoit
authors: B
authors: Blanchet
mesh_terms: D000970:Antineoplastic Agents / Q000097:blood* / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000097:blood* / Q000188:drug therapy; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D000069347:Erlotinib Hydrochloride; D000077156:Gefitinib; D006801:Humans; D008175:Lung Neoplasms / Q000097:blood* / Q000188:drug therapy; D011799:Quinazolines / Q000097:blood* / Q000627:therapeutic use; D013056:Spectrophotometry, Ultraviolet / Q000379:methods*
chemical_list: D000970:Antineoplastic Agents; D011799:Quinazolines; D000069347:Erlotinib Hydrochloride; D000077156:Gefitinib