不同HPLC检查瑞格列奈片有关物质的对比研究

Investigation on Different HPLC to Determine the Related Substances of Repaglinnide Tablets

关键词:  瑞格列奈  有关物质  系统适用性  高效液相色谱

Key words:  repaglinide  related substance  system suitability  HPLC

摘要:

目的 寻找合适的HPLC检查中国药典2010年版(Ch.P 2010)二部收载的瑞格列奈片的有关物质。方法 分别试验了Ch.P 2010、美国药典37版(USP 37)和欧洲药典2014版(EP 2014)所载瑞格列奈原料药及片剂有关物质检查的4种HPLC，考察了这4种方法的流动相稳定性、色谱柱耐用性和有关物质检出灵敏度。结果 Ch.P 2010所载方法的流动相B析出大量结晶。EP 2014方法的色谱柱耐用性较差，在试验的3种色谱柱中，只有1种色谱柱能达到分离度要求。USP 37所载的瑞格列奈片剂方法分析耗时较长，使主要杂质峰型变宽，检出灵敏度降低。只有USP 37所载的瑞格列奈原料药有关物质检查方法同时具备流动相稳定、对主要杂质有很好的检出灵敏度和优秀的色谱柱耐用性等优点。结论 Ch.P 2010所载瑞格列奈有关物质检查方法应作修改。USP 37所载瑞格列奈原料药有关物质检查方法可以大幅提高检测效率，是最适合Ch.P 2010收载的瑞格列奈片有关物质检查的方法。

Abstract:

OBJECTIVE To find a suitale HPLC method to determine the related substances of repaglinide tablets recorded in Ch.P 2010. METHODS The performances of 4 kinds of HPLC which recorded in Ch.P 2010, USP 37 and EP 2014 were tested. The stability of mobile phase, ruggedness of the chromatographic column and detection sensitivity were comprehensively surveyed. RESULTS A large amount of crystals were precipitated in the mobile phase B of Ch.P 2010. Only one out of three chromatographic columns met the resolution requirement using EP 2014 method, which indicating the ruggedness of chromatographic column was poor in this method. In the method of USP 37 for repaglinide tablets, the retention time of the main impurity was too long and its peak became wider so that the detection sensitivity was reduced. The method of USP 37 for repaglinide had the advantages of mobile phase stability, excellent detection sensitivity and ruggedness of chromatographic column. CONCLUSION The method of Ch.p 2010 should be modified. The method of USP 37 for repaglinide is best fit the determination of the related substances is no more essential.