LC-MS同时测定醋酸卡泊芬净中的3种杂质

Simultaneous Determination of Three Impurities in Caspofungin Acetate by LC-MS

关键词:  醋酸卡泊芬净  杂质  液相色谱-质谱联用

Key words:  caspofungin acetate  impurity  LC-MS

摘要:

目的 建立同时测定醋酸卡泊芬净中杂质A、C和D的LC-MS方法。方法 色谱柱为Waters CORTECS^® C₁₈⁺（4.6 mm×150 mm，2.7 μm）色谱柱；流动相A为0.1%甲酸-水溶液，流动相B为0.1%甲酸-乙腈；用电喷雾离子化单四极杆质谱，以选择离子检测方式对杂质A和C进行正离子检测，对杂质D进行负离子检测。结果 杂质A、C和D在线性范围内线性系数r≥0.9993；平均回收率分别为100.5%，104.1%和105.2%，RSD<4%（n=6）；按S/N=10计算，杂质A、C和D的定量限分别为31.8，6.99，15.5 ng·mL^–1。3批样品中杂质A、C和D的含量均低于限度值。结论 该方法简单、灵敏度高、适用性强，可用于醋酸卡泊芬净中杂质A、C和D的同时定量检测，并可为醋酸卡泊芬净中其他杂质检测提供参考。

Abstract:

OBJECTIVE To develop LC-MS method for the simultaneous determination of impurities A, C, and D of caspofungin acetate. METHODS Waters CORTECS^® C₁₈⁺(4.6 mm×150 mm, 2.7 μm) was used as the chromatography column. Mobile phase A and B were 0.1% formic acid-H₂O and 0.1% formic acid-CH₃CN, respectively. Electrospray ion source-single quadrupole mass spectrometry was used to detect impurities A and C in positive ion mode and impurity D in negative ion mode. RESULTS The correlation coefficient r was ≥ 0.9993 in linearity ranges of impurities A, C and D. The average recoveries were 100.5%, 104.1% and 105.2%, respectively, with RSD<4%(n=6). The LOQs (S/N=10) of impurities A, C and D were 31.8, 6.99 and 15.5 ng·mL^-1 respectively. The contents of impurities A, C and D in the three samples were all below the limits. CONCLUSION The developed LC-MS method is simple, sensitive, and applicable, which can be used to simultaneously determine impurities A, C and D in caspofungin acetate and can also provide a reference for the detection of other impurities in caspofungin acetate.