LC-MS-MS Determination of Imatinib and N-Desmethyl Imatinib in Human Plasma
2013; Oxford University Press; Volume: 52; Issue: 4 Linguagem: Inglês
10.1093/chromsci/bmt037
ISSN1945-239X
AutoresYue Zhang, Shuping Qiang, Zhi‐Ling Yu, Wei Zhang, Zhengrong Xu, Lifang Yang, Aidong Wen, Tian Hang,
Tópico(s)Chronic Lymphocytic Leukemia Research
ResumoA specific and sensitive liquid chromatography–electrospray ionization–tandem mass spectrometric method was developed for the quantification of imatinib and its primary metabolite N-desmethyl imatinib in human plasma. Protein precipitation with methanol was used for sample preparation. High-performance liquid chromatographic separation was performed on a Thermo BDS Hypersil C18 column (4.6 × 100 mm, 2.4 µm) with methanol–water (55:45, v/v) containing 0.1% formic acid and 0.2% ammonium acetate as the mobile phase, using isocratic elution at a flow rate of 0.7 mL/min. Detection was conducted with positive electrospray ionization multiple reaction monitoring of the ion transitions at m/z 494 → 394 for imatinib, 480 → 394 for N-desmethyl imatinib and 297 → 110 for the internal standard (palonosetron). The assay was validated in the concentration ranges of 8–5,000 ng/mL for imatinib and 3–700 ng/mL for N-desmethyl imatinib. The quantification limits for imatinib and N-desmethyl imatinib were 8 and 3 ng/mL, respectively. The intra-day and inter-day precision values of the assay (expressed as percentage relative standard deviation) were less than 15% at all concentration levels within the tested range, and the accuracy values were between 85 and 115%. The established method was successfully applied to the pharmacokinetic study of imatinib mesylate capsules in 24 healthy Chinese volunteers.
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