Development and application of a novel method for the determination of imatinib and N-desmethylimatinib in plasma based on molecularly imprinted sorbent in a solid-phase extraction process combined with liquid chromatography mass spectrometry detection

In this study, a novel method for the determination of imatinib (IMT) and N-desmethylimatinib (N-IMT) in plasma, based on molecularly imprinted polymer (MIP) as a sorbent in the solid-phase extraction process combined with liquid chromatography mass spectrometry detection was developed. Dual-monomer strategy was used to produce the sorbent with sufficient binding capacity towards IMT, and structural analogue of IMT was applied as the template molecule. It was found that dual-monomer systems, viz. itaconic acid-acrylamide, methacrylic acid-acrylamide or 4-vinylbenzoic acid-acrylamide, resulted in 10 to 20 times higher binding capacity than mono-monomer system using neat acrylamide. The highest binding capacity was noted for the MIP prepared from itaconic acid-acrylamide crosslinked with ethylene glycol dimethacrylate, 341 ± 19 ng g⁻¹, and specificity defined by affinity factor equal to nearly 1.3. The computational analysis helped to explain the reasons underlying the adsorption behavior of MIPs. The microscopic measurements and porosity data confirmed the extension of the surface of selected MIP system, with specific surface area equal to 237.2 m² g⁻¹. The spectroscopic analyses confirmed the composition of the MIP containing 71.5 ± 2.3 %wt of C and 5.2 ± 1.5 %wt of N atoms, respectively. The novel method was successfully applied to the pharmacokinetic analysis of a 400 mg imatinib mesylate film-coated tablet formulation in three healthy fasting subjects. The obtained pharmacokinetic parameters for IMT and N-IMT fell within the uncertainty range with AUC_0-∞ of 32,700 ± 2300 h μg L⁻¹ and 6400 ± 3400 h μg L⁻¹, respectively.