LC-MS/MS法测定阿贝西利原料药的7种有关物质

Determination of seven Related Substances in Abemaciclib by LC-MS/MS

关键词:  阿贝西利  原料药  有关物质  液相色谱-质谱联用  质量控制  分析方法

Key words:  abemaciclib  API  related substances  LC-MS/MS  quality control  analysis method

摘要:

目的： 建立液相色谱-质谱联用(LC-MS/MS)法测定阿贝西利原料药中的7种有关物质。方法： 使用液相色谱-三重四级杆质谱联用仪,采用安捷伦ZORBAX Eclipse Plus C18(2.1×100 mm,1.8 μm)色谱柱,0.01 mol·L-1甲酸铵水溶液(用氨水调节pH至9.0)为流动相A,以乙腈为流动相B,梯度洗脱,流速为0.3 mL·min-1,柱温40 ℃；电喷雾离子源,扫描方式为正离子扫描模式-多反应监测(MRM)。结果：遗传毒性警示结构杂质V的线性范围为0.0976～9.761 ng·mL-1(r=0.999 48)；杂质I、杂质II、杂质III、杂质IV、杂质VI和杂质VII的线性范围分别为19.44～583.08 ng·mL-1(r=0.999 30)、19.53～586.00 ng·mL-1(r=0.999 75)、22.26～667.92 ng·mL-1(r=0.999 29)、20.75～622.64 ng·mL-1(r=0.999 02)、20.52～615.65 ng·mL-1(r=0.999 71)、21.17～635.04 ng·mL-1(r=0.997 05)；精密度、重复性试验的RSD均小于3%；杂质V的平均回收率为95.4%(RSD=3.60%),杂质I、杂质II、杂质III、杂质IV、杂质VI和杂质VII的平均回收率为为95.4%～97.4%,RSD为0.16%～3.67%。结论： 所建立的LC-MS/MS方法准确、灵敏、专属性强,可为阿贝西利原料药的质量控制提供依据。

Abstract:

OBJECTIVE To establish a LC-MS/MS method for determination of seven related substances in Abemaciclib. METHODS A LC-triple quadrupole mass spectrometer with Agilent ZORBAX Eclipse Plus C18 (2.1×100 mm,1.8 μm) column was used. The mobile phase A was 0.01 mol·L-1 Ammonium formate solution (pH adjusted to 9.0 with Ammonia water) and The mobile phase B was acetonitrile. The whole run carried out by gradient elution at a flow rate of 0.3 mL·min-1, The column temperature was 40 ℃; The source was ESI+, scanned in MRM mode. RESULTS The linear range of the genotoxicity warning structural impurity V is 0.0976-9.761 ng·mL-1(r=0.999 48);The linear range of impurity I, impurity II, impurity III, impurity IV, impurity VI and impurity VII were19.44-583.08 ng·mL-1(r=0.999 30), 19.53-586.00 ng·mL-1(r=0.999 75), 22.26-667.92 ng·mL-1(r=0.999 29), 20.75-622.64 ng·mL-1(r=0.999 02), 20.52-615.65 ng·mL-1(r=0.999 71), 21.17-635.04 ng·mL-1(r=0.997 05); RSDs of precision and repeatability tests were all lower than 3%; The average recovery rate of impurity V was 95.4% (RSD=3.60%); The average recoveries of impurity I, impurity II, impurity III, impurity IV, impurity VI and impurity VII were 95.4%-97.4%, The RSD ranged from 0.16% to 3.67%. CONCLUSION The method has high sensitivity, specificity and accuracy, and can be used for the determination of the related substances of Abemaciclib.