关键词: font-size:medium, ">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

Abstract: 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 1.18-23.68 μg·mL-1 and 1.58-31.50 μg·mL-1， and the correlation coefficients r were 0.999 8 and 1.000， respectively. The detection limits were 0.36 μg·mL-1 and 0.47 μg·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.
 

Key words: font-size:medium, ">Headspace gas chromatography； Cytarabine； Genotoxic impurities； Hydrochloride API； Chloromethane； Chloroethane