Development of a simple and stability-indicating RP-HPLC method for determining olanzapine and related impurities generated in the preparative process.

摘要

A simple and stability-indicating reverse phase high performance liquid chromatographic (RP-HPLC) method was developed and validated for the determination of olanzapine (OLN) and related impurities in bulk drugs. Eight impurities were characterized respectively, and particularly a new process impurity from OLN synthesis was structurally confirmed as 1-(5-methylthionphen-2-yl)-1H-benzimidazol-2(3H)-one (Imp-7) by X-ray single crystal diffraction, MS, (1)H NMR, (13)C NMR and HSQC. A mechanism of formation pathway for Imp-7 was proposed. Optimum separation for OLN and eight related impurities was carried out on an Agilent Octyldecyl silica column (TC-C(18), 4.6 mm × 250 mm, 5 μm) using a gradient HPLC method. The method was validated with respect to specificity, linearity, accuracy, precision, LOD and LOQ. Regression analysis showed good correlation (r(2) > 0.9985) between the investigated component concentrations and their peak areas within the test ranges for OLN and eight impurities. The repeatability and intermediate precision, expressed as RSD, were less than 1.74%. The proposed stability-indicating method was suitable for routine quality control and drug analysis of OLN in bulk drugs.