液相色谱-高分辨质谱法测定盐酸雷尼替丁中N-亚硝基二甲胺的含量

Determination of contents of NDMA in ranitidine hydrochloride substances and products by LC-HRMS

目的 建立液相-高分辨质谱(LC-HRMS)法测定盐酸雷尼替丁原料药及制剂中N-亚硝基二甲胺(NDMA)的方法。方法 采用以十八烷基键合相硅胶为填料的色谱柱(100 mm×4.6 mm,3μm),以0.1%甲酸-水为流动相A,以0.1%甲酸-乙腈为流动相B,线性梯度洗脱,质谱电喷雾正离子化平行反应监测。结果 NDMA在0.5~100 ng·mL^(-1)范围内线性关系良好;检测限和定量限分别达0.3和0.5 ng·mL^(-1),平均加样回收率在82.9%~119.2%的范围内,应用该方法检测的10批样品中NDMA含量在0.000 002%~0.000 014%。结论 建立的LC-HRMS测定法专属性好、灵敏度高,适用于盐酸雷尼替丁原料及其制剂中痕量NDMA基因毒性杂质的检查与控制。

Objective To establish an LC-HRMS method for the determination of NDMA genotoxic impurities of analogs of ranitidine substances and products.Methods The separation was carried out on a C18 column(100 mm×4.6 mm,3 μm)by liner gradient elution using 0.1% formic acid as mobile phase A and 0.1% formic acid acetonitrile as mobile phase B.The HRMS determination of NDMA was conducted by means of positive electrospray ionization parallel reaction monitoring using the internal reference method.Results Linear calibrations were established for NDMA in the range of 0.5 to 100 ng·mL^(-1).The limits of detection and quantification proved to be as low as 0.3 and 0.5 ng·mL^(-1) respectively.The average recoveries were between 82.9% and 119.2%.The content of NDMA in the 10 samples detected with this method ranged from 0.000 002% to 0.000 014%.Conclusion The established LC-HRMS method has been validated to be suitable for the simultaneous quantitative determination of NDMA genotoxic impurities in ranitidine.