盐酸利多卡因注射剂遗传毒性杂质研究

Profiling of genotoxic impurities in a lidocaine hydrochloride injection

确定2,6-二甲基苯胺为盐酸利多卡因注射液中遗传毒性杂质,N-氯乙酰-2,6-二甲基苯胺为潜在遗传毒性杂质,建立LC-MS/MS方法,用色谱柱Agilent ZORBAX Eclipse Plus C18(4.6 mm×250 mm,5μm)对原料、自制制剂及原研制剂进行遗传毒性杂质研究。研究结果表明自制制剂中杂质2,6-二甲基苯胺与N-氯乙酰-2,6-二甲基苯胺除由原料引入外,可能分别由氧化条件或碱性条件下降解引入,为盐酸利多卡因注射液的遗传毒性风险评估和工艺优化提供参考与指导。

2,6-dimethylbenzenamine was determined as a genotoxic impurity in lidocaine hydrochloride injection,and 2-chloro-N-(2,6-dimethylphenyl)acetamide was determined as potential genotoxic impurity.An LC-MS/MS method was established to research the profiling of genotoxic impurities in active pharmaceutical ingredients(API),homemade preparation and reference preparation on column Agilent ZORBAX Eclipse Plus C18(4.6 mm×250 mm,5μm).The results show that in the homemade preparation the 2,6-dimethylbenzenamine and the 2-chloro-N-(2,6-dimethylphenyl)acetamide may be degraded under oxidation condition and alkaline condition in addition to the introduction from API preparation process.This study provides guidance for genotoxic risk assessment and prescription process optimization of lidocaine hydrochloride.