Imatinib quantification in human serum with LC-MS3 as an effective way of protein kinase inhibitor analysis in biological matrices.

BACKGROUND: As imatinib gained a lot of attention in the field of medicine, appropriate methods are needed for drug analysis. LC-MS/MS combined with complex sample preparation and column enrichment is usually the method of choice when high sensitivity is necessary. The application of LC-MS3 in imatinib quantification has not been discussed in the literature.

METHODS: An LC-MS3 imatinib quantification method was developed and validated in human serum. The sample preparation was based on the liquid-liquid extraction of 50 μL human serum. Chromatographic separation was performed using a Luna 5 μm C18 (2) 100 A, 150 mm×2 mm column and the elution was done using a mobile phase consisting of A (H2O/methanol=95/5, v/v) and B (H2O/methanol=3/97, v/v), both with 10 mM ammonium acetate and 0.1% acetic acid.

RESULTS: The conditions applied resulted in a limit of detection/quantification value of 0.14/0.45 ng/mL reached without a sophisticated sample preparation technique or enrichment column application. It could be demonstrated that MS3 detection is a very effective way of sensitive imatinib quantification. Further, it could be stated that the strategy presented can be very useful for a sensitive analysis of other protein kinase inhibitors, because their molecule structure is appropriate for MS3 detection.

CONCLUSIONS: The presented analytical strategy is an effective way of protein kinase inhibitor analysis in human serum.