title: A method to quantify several tyrosine kinase inhibitors in plasma by micellar liquid chromatography and validation according to the European Medicines Agency guidelines.
abstract: A procedure based on micellar liquid chromatography has been developed to monitor five tyrosine kinase inhibitors in plasma, prescribed against several kinds of cancer: erlotinib, imatinib, sunitinib, sorafenib and lapatinib. The sample was diluted in a micellar solution and directly injected, thus clean-up steps were not required. The analytes were resolved without interferences in <20 min using a C18 column and a mobile phase of 0.13 M SDS-4% 1-butanol, buffered at pH 3.5, running under isocratic mode at 1 mL/min. The detection was performed by UV-visible absorbance, using a wavelength program to maximize the signal-to-noise ratio. The method was validated following the guideline of the European Medicines Agency in terms of: selectivity, calibration range (0.05-5 μg/mol), linearity (r(2)>0.990), limit of detection (15-35 ng/mL), carry-over effect, accuracy (-10.4 to +11.0%), precision (<9.2%), matrix effect, robustness (<8.4%) and stability. The procedure is rapid, easy-to-handle, uses a low amount of toxic chemical provide reliable results. Finally, the method was successfully used to analyze the studied tyrosine kinase inhibitors in plasma from cancer patients.
authors.affiliation: Departamento de Química Física i Analítica, ESTCE, Universitat Jaume I, 12071 Castelló, Spain.
authors.forename: Iris
authors.initials: I
authors.lastname: Garrido-Cano
authors.affiliation: Departamento de Química Física i Analítica, ESTCE, Universitat Jaume I, 12071 Castelló, Spain.
authors.forename: Aurelio
authors.initials: A
authors.lastname: García-García
authors.affiliation: Departamento de Química Física i Analítica, ESTCE, Universitat Jaume I, 12071 Castelló, Spain.
authors.forename: Juan
authors.initials: J
authors.lastname: Peris-Vicente
authors.affiliation: Biopatologia Molecular, Hospital Provincial, Castelló, Spain.
authors.forename: Enrique
authors.initials: E
authors.lastname: Ochoa-Aranda
authors.affiliation: Departamento de Química Física i Analítica, ESTCE, Universitat Jaume I, 12071 Castelló, Spain. Electronic address: josep.esteve@uji.es.
authors.forename: Josep
authors.initials: J
authors.lastname: Esteve-Romero
mesh_terms: D000970:Antineoplastic Agents / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use; D001774:Blood Chemical Analysis / Q000379:methods*; D000440:Butanols / Q000737:chemistry; D002138:Calibration; D002853:Chromatography, Liquid / Q000379:methods*; D005060:Europe; D006801:Humans; D006863:Hydrogen-Ion Concentration; D057230:Limit of Detection; D008823:Micelles; D009369:Neoplasms / Q000188:drug therapy; D017410:Practice Guidelines as Topic; D047428:Protein Kinase Inhibitors / Q000097:blood* / Q000494:pharmacology / Q000627:therapeutic use; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D012955:Societies, Medical; D012967:Sodium Dodecyl Sulfate / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D000440:Butanols; D008823:Micelles; D047428:Protein Kinase Inhibitors; D012967:Sodium Dodecyl Sulfate; D011505:Protein-Tyrosine Kinases
keywords: Direct injection; Micellar; Plasma; Tyrosine kinase inhibitors; Validation