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
Highlights
An important role of vascular endothelial growth factor receptor (VEGF) in quite a few tumor forms has been reported.[1,2,3] The dysregulation of platelet derived growth factor (PDGF)[4] and epidermal growth factor (EGF)[5] play an important role in propagation of tumor cell
HPLC is widely used in quality control, pharmaceutical analysis and clinical settings as it provides acceptable sensitivity, more convenient and cheaper
PAZ contains a chromophore center (Fig. 1) and a method based on UV detection was developed and validated for estimation of PAZ in bulk and dosage form for quality control (QC) analysis
Summary
An important role of vascular endothelial growth factor receptor (VEGF) in quite a few tumor forms has been reported.[1,2,3] The dysregulation of platelet derived growth factor (PDGF)[4] and epidermal growth factor (EGF)[5] play an important role in propagation of tumor cell. Pazopanib (PAZ; GW-786034) chemically known as 5-({4-[(2,3-Dimethyl-2H-indazol-6-yl) (methyl) amino]-2-pyrimidinyl}amino)-2-methylbenzene-sulfonamide (Fig. 1) is tyrosine kinase inhibitor (multi-targeted and orally active). The targets for PAZ are VEGFR-1, -2, and -3, PDGFR-a, PDGFR-b, c-Kit and act by inhibiting auto-phosphorylation of growth factor receptor (intracellular TK domain). PAZ competes with ATP to bind to the intracellular TK domain blocking downstream signal transduction.[6] The recommended dose of PAZ is not more than 800 mg once daily for treatment of soft tissue sarcoma or renal cell carcinoma. Pharmacokinetic studies have revealed peak plasma concentration of 58.1 μg mL–1 and mean AUC of 1037 μg h mL–1 for PAZ after a dose of 50–2000 mg. PAZ is 99 % plasma protein bound and is eliminated mainly through feces and around 4 % through renal route.[7]
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