衍生化-顶空气相色谱法测定环丙沙星及其盐酸盐中痕量基因毒性杂质硫酸二甲酯

Development and validation of derivation-headspace gas chromatography method for ultra trace-level determination of genotoxic impurity dimethyl sulfate in ciprofloxacin and its hydrochloride

关键词:  环丙沙星  硫酸二甲酯  衍生化  顶空气相色谱法  残留量

Key words:  Ciprofloxacin  Dimethyl sulfate  Derivatization  HS-GC  Residual amount

摘要:

目的 建立衍生化-顶空气相色谱法测定环丙沙星及其盐酸盐中痕量基因毒性杂质硫酸二甲酯的残留量。方法 以碘化钠为衍生化试剂,使硫酸二甲酯发生烷基化反应生成碘甲烷,通过测定碘甲烷计算硫酸二甲酯的含量；采用DB-Wax毛细管柱(30m×0.53mm,1.0μm),程序升温,初始温度为 60℃,维持2min,以40℃/min升到180℃,维持2 min；以氮气为载气,流速为3.0 ml/min,检测器为ECD。结果 空白试验基本无干扰；硫酸二甲酯在8.5 ~63.4 ng.ml_-1^范围内线性关系良好(相关系数r为0.999)；定量限浓度为2.1ppb；环丙沙星和盐酸环丙沙星中硫酸二甲酯的加标回收率分别为89.3%和86.6% (n=9)。测得6批样品硫酸二甲酯残留量均小于定量限。结论 本方法操作简便,准确度高,灵敏度高,耐用性好,可用于检测环丙沙星及其盐酸盐中痕量级硫酸二甲酯的残留量。

Abstract:

Objective To establish a derivation-headspace gas chromatography method for the determination of ultrattrace genotoxic impurity dimethyl sulfate in ciprofloxacin and its hydrochloride. Methods Using sodium iodide as derivatization reagent, dimethyl sulfate was alkylated to produce iodomethane. The content of dimethyl sulfate was calculated by measuring iodomethane. Column was DB-Wax (30m×0.53mm, 1.0μm),Carrier gas is nitrogen.The flow rate is 3.0ml.min_-1^{. The detector is} ECD.The initial temperature was 60℃,hold 2min, then the temperature was raised to 180℃ at 40℃/min, hold 2min. Results There is no interference in the blank test. The linear relationship of Dimethyl sulfate in the range of 8.5~63.4 ng.ml_-1 was good(r=0.999),The LOQ is 2.1ppb. The average recovery were 89.3% and 86.6% (n=9) in ciprofloxacin and ciprofloxacin hydrochloride. The residues of dimethyl sulfate in 6 batches of samples are all lower than the LOQ. Conclusion The established method is simple, accurate,sensitive and durable for limit test and quantitative analysis of dimethyl sulfate in ciprofloxacin and its hydrochloride.