Development and validation of a sensitive LC–MS/MS method for determination of gefitinib and its major metabolites in human plasma and its application in non-small cell lung cancer patients

In this study, we established and validated a method for determining gefitinib and its main metabolites, M605211, M387783, M537194 and M523595 in patients with non-small cell lung cancer (NSCLC) by liquid chromatography–tandem mass spectrometry (LC–MS/MS) method. The mobile phase was water: acetonitrile (35:65, v/v) with 0.1% formic acid at a flow‐rate of 0.35 mL/min, within a 3 min run time. Gefitinib and its main metabolites were separated on a X-Terra RP18 column (50 × 2.1 mm, 3.5 μm) at 40 ℃ and subjected to mass analysis using positive electro-spray ionization (ESI). The calibration ranges of gefitinib and M523595 were 0.5–1000 ng/mL, and other compounds were 0.05–100 ng/mL with the correlation coefficients (r2) ≥ 0.99. Accuracies ranged from 92.60%–107.58 and the inter- and intra-assay precision were less than 15% for all analytes in quality control samples. There was no significant matrix effect. The ranges of extraction recoveries were 86–105% for all analytes and IS. Thirty plasmas were obtained from Sun Yat-sen university cancer center. The mean plasma concentration of (± SD) of gefitinib M537194, M523595, M387783 and M605211 were 247.18 (± 140.39) ng/mL, 7.78 (± 6.74) ng/mL, 101.09 (± 93.44) ng/mL, 1.6 (± 0.9) ng/mL and 11.63 (± 4.98) ng/mL, respectively. The validated LC/MS/MS method was effectively used in the determination of gefitinib and its four metabolites in NSCLC patients.
Source: Journal of Pharmaceutical and Biomedical Analysis - Category: Drugs & Pharmacology Source Type: research