title: An HPLC-UV method for the simultaneous quantification of vemurafenib and erlotinib in plasma from cancer patients.
abstract: Vemurafenib and erlotinib are two oral kinase inhibitors approved for the treatment of metastatic melanoma and advanced non-small cell lung cancer, respectively. In contrast with erlotinib, the single published method for analysis of vemurafenib in human plasma is based on mass spectrometry. The purpose of the present study was to develop an HPLC-UV method to simultaneously quantify these two drugs in plasma. Following liquid-liquid extraction, vemurafenib, erlotinib and sorafenib (internal standard) were separated isocratically on a C8 Xterra(®) MS using a mobile phase of glycine buffer (pH 9.0, 100mM)/acetonitrile (45:55, v/v). Samples were eluted at a flow rate of 0.9mL/min throughout the 12-min run. Dual UV wavelength mode was used, with vemurafenib and sorafenib monitored at 249nm, and erlotinib at 331nm. The calibration was linear in the range 1.25-100mg/L and 50-4000μg/L for vemurafenib and erlotinib, respectively. Inter- and intra-day precision was less than 6.7% and 6.6% for vemurafenib and erlotinib, respectively. This analytical method was successfully applied to assess the steady state plasma exposure of these drugs in cancer patients. This accurate method can be used in routine clinical practice to monitor vemurafenib or erlotinib concentrations in plasma from cancer patients.
authors.affiliation: Assistance Publique Hôpitaux de Paris, Hôpital Cochin, Unité Fonctionnelle de Pharmacocinétique et Pharmacochimie, Paris, France.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhen
authors.forename: Audrey
authors.initials: A
authors.lastname: Thomas-Schoemann
authors.forename: Lilia
authors.initials: L
authors.lastname: Sakji
authors.forename: Pascaline
authors.initials: P
authors.lastname: Boudou-Rouquette
authors.forename: Nicolas
authors.initials: N
authors.lastname: Dupin
authors.forename: Laurent
authors.initials: L
authors.lastname: Mortier
authors.forename: Michel
authors.initials: M
authors.lastname: Vidal
authors.forename: Francois
authors.initials: F
authors.lastname: Goldwasser
authors.forename: Benoit
authors.initials: B
authors.lastname: Blanchet
mesh_terms: D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D016903:Drug Monitoring / Q000379:methods*; D000069347:Erlotinib Hydrochloride; D006801:Humans; D007211:Indoles / Q000097:blood*; D059625:Liquid-Liquid Extraction / Q000379:methods; D008545:Melanoma / Q000188:drug therapy; D047428:Protein Kinase Inhibitors / Q000097:blood*; D011799:Quinazolines / Q000097:blood*; D012680:Sensitivity and Specificity; D013056:Spectrophotometry, Ultraviolet / Q000379:methods*; D013449:Sulfonamides / Q000097:blood*; D000077484:Vemurafenib
chemical_list: D007211:Indoles; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D013449:Sulfonamides; D000077484:Vemurafenib; D000069347:Erlotinib Hydrochloride