柱前衍生化UHPLC-Q-Orbitrap HRMS法测定乙酰唑胺及其胶囊剂中肼的含量  

Determination of hydrazine in acetazolamide and its capsules by UHPLC-Q-Orbitrap HRMS with precolumn derivatization

作　　者：梅芊[1] 李茜[1] 刘英[1] MEI Qian;LI Qian;LIU Ying(Henan Institute for Food and Drug Control,Zhengzhou 450018,China)

机构地区：[1]河南省食品药品检验所,郑州450018

出　　处：《药物分析杂志》2020年第8期1467-1472,共6页Chinese Journal of Pharmaceutical Analysis

摘　　要：目的:建立柱前衍生化超高效液相色谱-四极杆/静电场轨道阱高分辨质谱法(UHPLC-QOrbitrap HRMS)测定乙酰唑胺及其胶囊剂中肼的含量。方法:以苯甲醛为衍生化试剂,使用NanoChrom ChromCoreTM 120 C18(2.1 mm×150 mm,5μm)色谱柱,以5 mmol·L^-1甲酸铵水溶液(含0.1%甲酸)-乙腈(30∶70)为流动相,流速为0.4 mL·min^-1,正离子(ESI+)模式下平行反应监测(PRM)方式检测。结果:所建方法的专属性、重复性、稳定性均良好。肼的质量浓度在24.6~184.8 ng·mL^-1范围内线性关系良好(r=0.9997),原料的平均回收率为93.8%,胶囊剂的平均回收率为94.3%,9批次样品均未检出肼。结论:该方法简便快捷,准确可靠,适用于乙酰唑胺及其胶囊剂中肼的快速检测,也可为其他药物中肼类杂质的检测提供参考。Objective:To establish an ultra-high performance liquid chromatography-quadrupole-orbitrap high resolution mass spectrometry(UHPLC-Q-Orbitrap HRMS)method for the determination of hydrazine in acetazolamide and its capsules by precolumn derivatization. Methods:Hydrazine was derivatized with benzaldehyde,and was separated on NanoChrom ChromCoreTM 120 C18(2.1 mm×150 mm,5 μm)column with 5 mmol·L^-1 ammonium formate solution containing 0.1% formic acid-acetonitrile(30∶70)as a mobile phase. The flow rate was set at 0.4 mL·min^-1. The target compound was analyzed in the positive ion parallel reaction monitoring(PRM)mode. Results:The method showed good specificity,repeatability and stability. The linear range of hydrazine was 24.6-184.8 ng·mL^-1(r= 0.999 7),and the recovery values of drug substance and capsules were 93.8% and 94.3%,respectively. No hydrazine was detected in samples. Conclusion:The method was simple,accurate and reliable,and was suitable for the rapid detection of hydrazine in acetazolamide and its capsules. The method also provided a reference for the hydrazine impurities in other drugs.

关 键 词：柱前衍生化超高效液相色谱-四极杆/静电场轨道阱高分辨质谱法(UHPLC-Q-Orbitrap HRMS) 遗传毒性杂质 乙酰唑胺 肼 

分 类 号：R917[医药卫生—药物分析学]