摘要
目的:建立HPLC法测定氟康唑的有关物质,并对最大未知杂质进行结构鉴定。方法:采用CERI L-column ODS(250 mm×4.6 mm,5μm)色谱柱,以0.01 mol·L^(-1)醋酸钠缓冲液(pH 5.0)-甲醇(95∶5)为流动相A,乙腈-甲醇(60∶40)为流动相B,梯度洗脱,流速1.0 m L·min^(-1),检测波长261 nm,柱温30℃。用LC-MS分析最大未知杂质,再用半制备液相色谱分离纯化,通过NMR确定结构。结果:建立的HPLC有关物质分析方法具有良好的方法学验证结果,与中国药典方法比较,杂质检出能力更强;最大未知杂质为2-(2,4-二氟苯基)^(-1),3-二(1H^(-1),2,4-三唑^(-1)-基)-丁-2-醇。结论:建立的方法简便、灵敏,专属性好,杂质检出能力强,能有效地反应药品质量。
Objective：To establish an HPLC method for determination of related substances in fluconazole and to identify the structure of the largest unknown impurity.Methods：A CERI L-column ODS（250 mm×4.6 mm,5 μm）was adopted for the study with gradient elution.The mobile phase A was 0.01 mol·L（-1） sodium acetate buffer solution（pH 5.0）-methanol（95∶5）,and the mobile phase B was acetonitrile-methanol（60∶40）.The flow rate was 1.0 m L·min（-1）,the detection wavelength was 261 nm,and the column temperature was 30 ℃.The largest unknown impurity was analyzed by LC-MS,and was then separated and purified by semi-preparative HPLC,and its structure was confirmed by NMR.Results：The established and validated HPLC method showed stronger capacity for fluconazole related substances control compared to the method recorded in Chinese pharmacopoeia 2010.The largest unknown impurity was 2-（2,4-difluorophenyl）（-1）,3-bis（1H（-1）,2,4-triazol（-1）-yl）-butan-2-ol.Conclusion：The established HPLC method is simple,specific,sensitive and good at impurity inspection,which can be applied in the quality control and comparison of the marketed products from different manufacturers.
出处
《药物分析杂志》
CAS
CSCD
北大核心
2016年第7期1243-1251,共9页
Chinese Journal of Pharmaceutical Analysis
