Determination of Tyrosine Kinase Inhibitor Icotinib in Rat Plasma using UPLC-MS/MS and its Application In vivo Pharmacokinetic
CURRENT PHARMACEUTICAL ANALYSIS(2024)
Abstract
Objective: The purpose of this study was to develop a UPLC-MS/MS method for the determination of icotinib concentrations in blood plasma. Methods: For plasma sample preparation, protein precipitation with acetonitrile was utilized. Analytes were separated on a Kinetex C18 column using 10 mM ammonium acetate containing 0.2% formic acid and methanol (30:70) as the mobile phase, with a gradient flow rate ranging from 0.2 mlmin-1 to 0.4 mlmin-1. The total chromatographic analysis duration was 4.5 minutes. The UPLC system was connected to a mass spectrometer via an electrospray ionization (ESI) interface operated in positive ion mode. Mass monitoring was conducted in multiple reaction monitoring (MRM) modes, with precursor-to-product transitions being m/z 392.06 -> 304.07 for icotinib and m/z 248.00 -> 120.09 for the internal standard, tinidazole. This method has been used for a pharmacokinetic study in rats that were orally administered a single dose of 30 mg/kg icotinib. Results: The assay showed good linearity over concentration ranges of 1-1000 ng/ml for icotinib, with the correlation coefficient exceeding 0.99. The lower limit of quantitation (LLOQ) was established at 1 ng/ml. Both intra- and inter-day precisions (RSD, %) were below 8.23%. The results demonstrated that stability, matrix effect, extraction recovery, carryover effect and dilution stability were all within the acceptable conditions. The primary pharmacokinetic parameters in SD rats after oral administration of icotinib (30 mgkg(-1)) were as follows: t1/2 = (2.92 +/- 0.87)h, C-max = (2168.65 +/- 268.72)ng/ml, Tmax = (0.70 +/- 0.27)h, AUC=(9.69 +/- 1.95)ug/mL center dot h, Vd = (14.51 +/- 5.60)L, and CL = (3.19 +/- 0.59)L/h. Conclusion: A simple and sensitive UPLC-MS/MS method was developed and validated for the determination of icotinib in pharmacokinetic studies.
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Key words
Icotinib,pharmacokinetic,rat,UPLC-MS/MS,plasma,ESI
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