Simple and selective method for the determination of various tyrosine kinase inhibitors used in the clinical setting by liquid chromatography tandem mass spectrometry

Autor: Egbert F. Smit, Henk M.W. Verheul, Elisa Giovannetti, Joline S.W. Lind, Richard J. Honeywell, Carmelo Tibaldi, K. Yarzadah, Nienke Losekoot, G.J. Peters, Maudy Walraven
Přispěvatelé: Medical oncology laboratory, Pulmonary medicine, Medical oncology, CCA - Disease profiling
Rok vydání: 2010
Předmět:
Zdroj: Honeywell, R J, Yarzadah, K, Giovannetti, E, Losekoot, N, Smit, E F, Walraven, M, Lind, J S W, Tibaldi, C, Verheul, H M W & Peters, G J 2010, ' Simple and selective method for the determination of various tyrosine kinase inhibitors used in the clinical setting by liquid chromatography tandem mass spectrometry ', Journal of Chromatography B, vol. 878, no. 15-16, pp. 1059-1068 . https://doi.org/10.1016/j.jchromb.2010.03.010
Journal of Chromatography B, 878(15-16), 1059-1068. Elsevier
ISSN: 1570-0232
Popis: A fast, sensitive, universal and accurate method for the determination of four different tyrosine kinase inhibitors from biological material was developed using LC-MS/MS techniques. Utilizing a simple protein precipitation with acetonitrile a 20 microl sample volume of biological matrixes can be extracted at 4 degrees C with minimal effort. After centrifugation the sample extract is introduced directly onto the LC-MS/MS system without further clean-up and assayed across a linear range of 1-4000 ng/ml. Chromatography was performed using a Dionex Ultimate 3000 with a Phenomenex prodigy ODS3 (2.0 mm x 100 mm, 3 microm) column and eluted at 200 microl/min with a tertiary mobile phase consisting of 20mM ammonium acetate:acetonitrile:methanol (2.5:6.7:8.3%). Injection volume varied from 0.1 microl to 1 microl depending on the concentration of the drug observed. Samples were observed to be stable for a maximum of 48 h after extraction when kept at 4 degrees C. Detection was performed using a turbo-spray ionization source and mass spectrometric positive multi-reaction-monitoring-mode (+MRM) for Gefitinib (447.1 m/z; 127.9 m/z), Erlotinib (393.9 m/z; 278.2 m/z), Sunitinib (399.1 m/z; 283.1 m/z) and Sorafenib (465.0 m/z; 251.9 m/z) at an ion voltage of +3500 V. The accuracy, precision and limit-of-quantification (LOQ) from cell culture medium were as follows: Gefitinib: 100.2+/-3.8%, 11.2 nM; Erlotinib: 101.6+/-3.7%, 12.7 nM; Sunitinib: 100.8+/-4.3%, 12.6 nM; Sorafenib: 93.9+/-3.0%, 10.8 nM, respectively. This was reproducible for plasma, whole blood, and serum. The method was observed to be linear between the LOQ and 4000 ng/ml for each analyte. Effectiveness of the method is illustrated with the analysis of samples from a cellular accumulation investigation and from determination of steady state concentrations in clinically treated patients.
Databáze: OpenAIRE