HPLC法测定氯氮平原料中有关物质的含量

Content Determination of Related Substance in Clozapine by HPLC

目的:建立测定氯氮平原料中有关物质含量的方法。方法:采用高效液相色谱法。色谱柱填充剂为十八烷基硅烷键合硅胶25,℃流。动考相察为了甲3醇个-水厂(家2090批m氯L水氮中平含原三料乙中胺有关0.7物5质mL的)=含7量0。∶30结,检果测:氯波氮长平为主2峰57与nm杂,质流峰速可为有1.0效m分L·离m,i经n-专1,进属样性量试为验、2定0μ量L,限柱、温耐为用性试验、溶液稳定性试验,认定方法可行,检出限为0.268ng。氯氮平原料中单一最大杂质含量均在0.5%以下,且杂质的总量不超过0.6%。结论:该方法简便可靠、专属性强,可用于氯氮平原料中有关物质的控制检查。

OBJECTIVE：To establish the method for the content determination of related substance in clozapine. METHODS： HPLC method was adopted. The chromatogram column was Agilent Zorbax 80A Extend-C18 with mobile phase consisted of methanol-water （0.75 mL triethylamine solved in 200 mL water, 70 ∶ 30） at the flow rate of 1.0 mL·min-1. The detection wavelength was set at 257 nm and injection volume was 20 μL. The volume temperature was 25 ℃. The content of related substance in 9 batches of clozapine from 3 manufacturers was investigated. RESULTS： Main peak and impurity peak of clozapine were separated effectively. The method was feasible confirmed by specificity test, quantitative limit, tolerance test and stability test. The detection limit was 0.268 ng. The maximum content of single impurity was below 0.5% and the total content of impurities was no more than 0.6%. CONCLUSION： The method is proved to be simple, reliable and specific for the quality control of related substance in clozapine.