顶空-气相色谱法测定阿糖胞苷原料药中基因毒杂质氯甲烷和氯乙烷  

Determination of Genotoxic Impurities Chloromethane and Chloroethane in Cytarabine APIs by Headspace Gas Chromatography

作　　者：杨海洋 王策 林妮妮 YANG Hai-yang;WANG Ce;LIN Ni-ni(Beijing Leadingpharm Medical Technology Development Co.,Ltd.,Beijing 100094,China)

机构地区：[1]北京新领先医药科技发展有限公司,北京100094

出　　处：《中国药物评价》2023年第4期309-312,共4页Chinese Journal of Drug Evaluation

摘　　要：目的:建立一种准确测定阿糖胞苷原料药中基因毒杂质氯甲烷和氯乙烷含量的气相色谱方法。方法:采用顶空气相色谱法,以氢火焰离子化检测器(FID)为检测器,DB-624毛细管柱为色谱柱,N,N-二甲基甲酰胺(DMF)为溶剂。检测器温度为250℃,进样口温度为200℃,柱温为程序升温。顶空平衡温度为80℃,顶空平衡时间为30 min。结果:氯甲烷和氯乙烷分别在1.18~23.68μg·mL^(-1)和1.58~31.50μg·mL^(-1)范围内呈现良好的线性,相关系数r分别为0.9998和1.000;检测限浓度分别为0.36μg·mL^(-1)和0.47μg·mL^(-1);低、中、高3个浓度的加标回收率分别介于97.3%~105.6%、105.9%~116.1%间;重复性试验的相对标准偏差分别为1.94%和2.10%。氯甲烷和氯乙烷的系统适用性、专属性和进样精密度均良好。结论:本方法操作简单,灵敏度高,成本较低,在阿糖胞苷原料药中的氯甲烷和氯乙烷的质量控制具有重要的现实意义,对于盐酸盐类原料药中氯甲烷、氯乙烷的质量控制具有重要参考价值。Objective:Established an accurate gas chromatography method for determination of the genotoxic impurities chloromethane and chloroethane in cytarabine active pharmaceutical ingredient(API).Methods:Headspace gas chromatography was performed with hydrogen flame ionization detector(FID)as detector,DB-624 capillary column as column,N,N-dimethylformamide(DMF)as solvent.The detector temperature was 250℃,inlet temperature was 200℃,and column temperature was programmed temperature.The headspace equilibrium temperature was 80℃and the headspace equilibrium time was 30min.Results:Chloromethane and chloroethane showed good linearity in the range of 1.18-23.68μg·mL^(-1)and 1.58-31.50μg·mL^(-1),and the correlation coefficients r were 0.9998 and 1.000,respectively.The detection limits were 0.36μg·mL^(-1)and 0.47μg·mL^(-1),respectively.The spiked recoveries were 97.3%-105.6%、105.9%-116.1%at three concentration levels(low,medium and high),respectively.The relative standard deviations of repeatability tests were 1.94%and 2.10%,respectively.Conclusions:The system applicability,specificity and injection precision of chloromethane and chloroethane were satisfactory.With simple operation,high sensitivity and low cost,this method has very important practical significance in the quality control of chlorothane and chloroethane in cytarabine apis,and has important reference value for the quality control of chlorothane and chloroethane in hydrochloride APIs.

关 键 词：顶空-气相色谱 阿糖胞苷 基因毒杂质 盐酸盐原料药 氯甲烷 氯乙烷 

分 类 号：R927.11[医药卫生—药学]