LC-MS/MS法测定2-脱氧-D-核糖中的甲磺酸甲酯和甲磺酸乙酯的含量

A convenient LC-MS/MS method for determination of methyl methanesulfonate and ethyl methanesulfonate in 2-deoxy-D-ribose

目的建立LC-MS/MS法检测2-脱氧-D-核糖中基因毒性杂质甲磺酸甲酯和甲磺酸乙酯的方法。方法选用C18色谱柱（以十八烷基硅烷键合硅胶为填充剂,250 mm×4.6 mm,5μm）,以甲醇-水（体积比30∶70）为流动相,流速为1.0 m L·min-1,分流比为30%,柱温为40℃,进样量为10μL。采用APCI离子源检测扫描方式负离子模式检测。结果甲磺酸甲酯和甲磺酸乙酯质量浓度在20～200μg·L-1内与峰面积线性关系良好,甲磺酸甲酯和甲磺酸乙酯的检测限为4μg·L-1,定量限为10μg·L-1,甲磺酸甲酯和甲磺酸乙酯的回收率分别为104.8%（RSD=7.93%,n=9）和101.0%（RSD=5.97%,n=9）。结论本方法灵敏、专属性强,适用于2-脱氧-D-核糖中基因毒性杂质甲磺酸甲酯和甲磺酸乙酯的检测。

Objective To establish a convenient LC-M S / M S analytical method for the determination of genotoxic impurities including methyl methanesulfonate and ethyl methanesulfonate in 2-deoxy-D-ribose. Methods The analysis was performed on C18（ 250 mm × 4. 6 mm,5 μm） column maintained at 40 ℃ with a mobile phase of methanol-water（ V ∶ V = 30 ∶ 70）. The flowrate was 1. 0 m L·min- 1. The split ratio was30% and 10 μL sample solution was injected into the LC-M S / M S system. Detection of the reference solution and the sample solution was carried out by APCI on a TSQ Quantum Ultra LC-M S / M S system. Results The assay of methyl methanesulfonate and ethyl methanesulfonate was linear over the range 20- 200μg·L- 1,with a limit of detection of 4 μg·L- 1and with a limit of quantitation of 10 μg·L- 1. The recovery were 104. 8%（ RSD was 7. 93%, n = 9） for methyl methanesulfonate and 101. 0%（ RSD was5. 97%,n = 9） for ethyl methanesulfonate,respectively. Conclusions The method is rapid,sensitive,selective,and reliable for the determination of genotoxic impurities including methyl methanesulfonate and ethyl methanesulfonate in 2-deoxy-D-ribose.