Simultaneous quantification of erlotinib, gefitinib, and imatinib in human plasma by liquid chromatography tandem mass spectrometry.
A quantitative liquid chromatography (LC)-mass spectrometry (MS)/MS method in human plasma was developed and validated for the tyrosine kinase inhibitors erlotinib, gefitinib, and imatinib in human plasma. Pre-treatment of the samples was achieved by using liquid-liquid extraction using D-8 imatinib as internal standard. Separation was performed on a Waters Alliance 2795 LC system using an XBridge RP18 column. The mass spectrometer Micromass was equipped with an electro spray ionization probe, operating in the positive mode. The calibration curves in plasma were linear for erlotinib, gefitinib, and imatinib over the concentration range of 5 to 3,000; 5 to 3,000, and 5 to 5,000 ng/mL, respectively. The intraday and interday accuracy ranged from 90% to 110% and the intraday and interday precision of the method was within 5%. The reported method provided the necessary linearity, precision, and accuracy to determine tyrosine kinase inhibitors in clinical research and for therapeutic drug monitoring.
VU University Medical Center, Department of Clinical Pharmacology and Pharmacy, Amsterdam, The Netherlands. a.chahbouni@vumc.nl
A
A
Chahbouni
J C G
JC
den Burger
R M
RM
Vos
A
A
Sinjewel
A J
AJ
Wilhelm
D053000:Analytic Sample Preparation Methods; D001549:Benzamides; D002138:Calibration; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D016903:Drug Monitoring / Q000379:methods; D000069347:Erlotinib Hydrochloride; D000077156:Gefitinib; D006801:Humans; D000068877:Imatinib Mesylate; D008832:Microchemistry; D010879:Piperazines / Q000097:blood*; D011743:Pyrimidines / Q000097:blood*; D011799:Quinazolines / Q000097:blood*; D015203:Reproducibility of Results; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods; D053719:Tandem Mass Spectrometry / Q000379:methods*
D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D011799:Quinazolines; D000068877:Imatinib Mesylate; D000069347:Erlotinib Hydrochloride; D000077156:Gefitinib