Quantification of imatinib and related compounds using capillary electrophoresis-tandem mass spectrometry with field-amplified sample stacking

Abstract A quantification method for imatinib (IM), its major metabolite N-desmethyl imatinib (NDI), and a degradation by-product was developed using CE–MS combined with an online concentration technique. The use of multiple reaction monitoring (MRM)–MS/MS further improved the sensitivity of this technology. Liquid–liquid extraction (LLE) using tertiary butyl methyl ether yielded high recovery and reproducibility for the pretreatment of serum samples. The recovery rate exceeded 83% for all three analytes, and was 90% for IM. To improve quantification results, a conductivity-induced online analyte concentration technique, field-amplified sample stacking (FASS), was used. The S/N ratios were improved at least 10-fold when compared with conventional capillary zone electrophoresis. The detection limits were 0.2 ng/mL for IM, 0.4 ng/mL for NDI, and 4 ng/mL for the degradation by-product. These results are superior to those previously obtained by other reported methods. The new method was validated in terms of its selectivity, intra- and interday repeatability and accuracy, and sample storage stability, following the guidelines issued by the European Medicines Agency. Considering the convenient pretreatment procedure (LLE), superior sensitivity, and fast analysis speed (<15 min), this method can be useful in the determination of imatinib levels in blood.