ICH guidelines-compliant HPLC-UV method for pharmaceutical quality control and therapeutic drug monitoring of the multi-targeted tyrosine kinase inhibitor pazopanib

Abstract

In this study, an HPLC method with ultraviolet (UV) detection was developed and validated for determination of pazopanib (PAZ), a multi-targeted tyrosine kinase (TK) inhibitor in bulk drug, tablets formulation, and in human plasma. Oxamniquine (OXA) was used as internal standard (IS). The analytical column used for the separation was Nucleosil CN with dimensions (i.d. 250 × 4.6 mm and particle size 5 μ m). The separation was carried out in isocratic mode with mobile phase constituting acetonitrile:100 mM sodium acetate buffer (pH 4.5); 40:60, v/v. The developed method was linear in the concentration range of 2–12 μ g mL –1 and had a correlation coefficient (r = 0.9998, n = 6). The limits of detection and quantitation (LOD and LOQ) were 0.27 and 0.82 μ g mL –1 , respectively. The relative standard deviations for the inter- and intra-assay precisions were below 3.61 % and the accuracy of the method was 96.69–104.15 %. The degradation products were resolved from the intact drug, proving the stability-indicating property of the proposed method. The recovery values were 100.17–103.98 % (± 1.81–4.02) for determination of PAZ in human plasma. The results indicated the versatility of the new method in estimation of PAZ during pharmaceutical quality control (QC) and therapeutic drug monitoring (TDM). Keywords: Tyrosine kinase inhibitors, pazopanib, HPLC, UV detection, quality control, therapeutic drug monitoring