Development and Clinical Validation of an HPLC-PDA Method for Imatinib Mesylate in Human Plasma: Interest in Therapeutic Drug Monitoring

Imatinib is the first-line treatment for Chronic Myeloid Leukemia (CML), it has favorable pharmacokinetic properties, but resistance mechanisms may lead to diminished clinical response over time. Therapeutic Drug Monitoring targeting trough plasma concentrations may help to optimize the therapeutic effect, or there is a correlation between imatinib concentrations and treatment response.

This study aimed to develop and validate a High-Performance Liquid Chromatographic method for the measurement of plasma concentrations of imatinib.

The analyte was extracted from a 500µl plasma sampler and separated on a RESTEK C18 column (5 µm, 250 x 4.6 mm). Propranolol was used as an internal standard. The analytes were detected with a UV Photodiode Array Detector (PAD) at 270 nm. Linearity, accuracy, precision, recovery, selectivity, and Limit of Detection (LOD) and Limit of Quantification (LOQ) in the sample compartment were evaluated according to the International Conference on Harmonization bio analytical guidelines method guideline M10.

The total run time was 7 min. The method appeared linear over a range from 0.2 to 10 µg/ml. Recovery was 98.2%-105%. The LOD and the LOQ were 200 ng/ml and 500 ng/ml, respectively. Our method appeared very suitable for therapeutic drug monitoring of imatinib.

The developed method was fully validated. It is a simple, rapid, practical, and less expensive method to determine imatinib plasma concentrations in CML patients.