摘要
目的:建立LC-MS法对甲磺酸伊马替尼原料中的3个磺酸酯基因毒杂质—甲磺酸甲酯(MMS)、甲磺酸乙酯(EMS)、甲磺酸异丙酯(IPMS)进行定量检测。方法:选用Agilent Poroshell 120 SB-C18色谱柱(2.7μm,4.6 mm×100 mm),以10mmol·L^-1甲酸铵(含0.1%甲酸)为流动相A,甲醇为流动相B,梯度洗脱[0 min(80%A-20%B)→5 min(10%A-90%B)→10 min(10%A-90%B)→10.5 min(80%A-20%B)→18.5 min(80%A-20%B)],流速为0.4 m L·min^-1。ESI正离子化SIM模式下对3种磺酸酯进行同时检测,雾化氮气压力0.3 MPa、温度300℃、流速10 L·min^-1,毛细管电压3 k V,传输电压30 V。结果:MMS在10-100 ng·m L^-1内线性关系良好(r=0.9988),定量限为10 ng·m L^-1;EMS在5-50 ng·m L^-1内线性关系良好(r=0.9992),定量限为5 ng·m L^-1;IPMS在10-100 ng·m L^-1内线性关系良好(r=0.9993),定量限为10 ng·m L^-1。MMS、EMS、IPMS的回收率分别为99.86%、101.7%、103.8%。结论:经方法学验证,该法可用于甲磺酸伊马替尼中3个磺酸酯基因毒杂质的同时检测,能为质量控制提供参考。
Objective:To determine three sulfonic acid esters, methyl methanesulfonate (MMS), ethyl methane- sulfonate (EMS), and isopropyl methanesulfonate (IPMS), known as potential carcinogenic and genotoxic impuri- ties in imatinib mesylate by liquid chromatography -mass spectrometry (LC -MS). Methods: The separation was carried out on a Poroshell SB - C18 column (2.7 μm, 4.6 mm × 100 mm) with the mobile phase consisting of 10 mmol · L^-1 ammonium formate containing 0. 1% (V/V) formic acid (A) and methanol (B) by gradient elution [0 min( 80% A - 20% B ) →5min ( 10% A - 90% B ) →10 min ( 10% A - 90% B ) →10.5 min ( 80% A - 20% B ) → 18.5 rain (80% A -20% B) ] at a flow rate of 0.4mL · min^-1. The results of quadrupole mass spectrometer was equipped with an ESI (in the positive mode). The conditions were as follows: nitrogen drying gas with nebulizer pressure of 0.3 MPa, the flow rate of 10 L · min^- 1 , the temperature of 300 ℃, the capillary voltage of 3 kV and the fragmentation voltage of 30 V. Results: The results of limit of quantification (LOQ) of MMS, EMS and IPMS were 10 ng · mL^-1, 5 ng · mL^-1 and 10 ng · mL^-1, respectively. Recoveries of MMS, EMS and IPMS were 99.86%, 101.7% and 103.8%, respectively. The linear calibration curves of MMS and IPMS were obtained over the concentration range of 10 - 100 ng · mL^-1, while the curve of EMS over 5 -50 ng · mL^-1. Conclusion: The methodology validation showed that this LC -MS method is useful as a quality control method for the simultaneous trace analysis of MMS, EMS and IPMS in imatinib mesylate.
出处
《药物分析杂志》
CAS
CSCD
北大核心
2014年第12期2202-2206,共5页
Chinese Journal of Pharmaceutical Analysis