Therapeutic Drug Monitoring of Imatinib and N‐Desmethyl Imatinib in Chronic Myeloid Leukemia Patients Using LC‐MS/MS in a Cohort Study

Abstract

AbstractImatinib is an oral tyrosine kinase inhibitor (TKI) and first‐line therapy for patients with chronic myeloid leukemia (CML). There is a positive correlation between serum imatinib concentrations and treatment response. However, the specific relationship between the blood concentration of imatinib and its influencing factors remains unclear. This study collected basic information from 102 patients using imatinib as first‐line treatment for CML. Further, we analyzed the individual differences in imatinib concentration and explored its influencing factors. Through intra‐day and inter‐day precision studies, we found that the precision for the imatinib assay methodology was within ±13% and that the recovery rate was above 85%. There is notable individual variation in the blood concentration of imatinib; the recommended treatment concentration is 860‐1500 ng/mL, with only 41.40% of patients achieving this concentration. Also, there was a negative correlation between age and imatinib trough concentration (Ctrough), as is observed between age and N‐desmethyl imatinib. Moreover, compared with the adolescent group, the serum imatinib Ctrough for groups aged 17‐47 and 48‐68 years was significantly reduced. Further analysis shows that imatinib Ctrough values reaching therapeutic concentrations (59%) increased dramatically for patients with CML aged 17‐47 years. Moreover, groups dosed with 400 mg/day resulted in therapeutic imatinib concentrations for 68% of patients with CML, which was the best performance. The established method was validated, with acceptable accuracy, precision, linearity, and stability, as required, and then successfully applied to the therapeutic drug monitoring of imatinib. Age, dose, and metabolites can influence the imatinib concentration and its therapeutic effect in patients with CML.