Title
Development of a simple and stability-indicating RP-HPLC method for determining olanzapine and related impurities generated in the preparative process
Author
Daoping Cui, Yueqing Li, Mingming Lian, Feng Yang and Qingwei Meng
Year
2011
Journal
Analyst
Abstract
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, 13C 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-C18, 4.6 mm 250mm, 5 mm) using a gradient HPLC method. The method was validated with respect to specificity, linearity, accuracy, precision, LOD and LOQ. Regression analysis showed good correlation (r2 > 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.
Instrument
HPLC
Keywords
HPLC, olanzapine, preparative, impurities, quality control