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论文类型：期刊论文

发表时间：2011-08-07

发表刊物：ANALYST

收录刊物：Scopus、SCIE、PubMed

卷号：136

期号：15

页面范围：3149-3156

ISSN号：0003-2654

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 x 250 mm, 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 (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.