Department of Pharmaceutical Analysis, China Pharmaceutical University, Nanjing, China.
Key Laboratory of Drug Quality Control and Pharmacovigilance, Ministry of Education, China Pharmaceutical University, Nanjing, China.
J Sep Sci. 2017 Sep;40(17):3414-3421. doi: 10.1002/jssc.201700543. Epub 2017 Aug 1.
Methanesulfonic acid is routinely used in pharmaceuticals but can contain potentially genotoxic impurities such as methyl methanesulfonate and ethyl methanesulfonate. The aim of this study was to develop a simple high-performance liquid chromatography with ultraviolet detection method for determining methyl methanesulfonate and ethyl methanesulfonate in methanesulfonic acid. Samples (250 mg) in water/acetonitrile (200 μL) were first combined with 10.0 mol/L sodium hydroxide solution (270 μL). Then they were mixed with 2.0 mg/mL N,N-diethyldithiocarbamate (500 μL), diluted to 5 mL with N,N-dimethylacetamide and allowed to react at 80°C for 1 h. The derivatives were analyzed using gradient high-performance liquid chromatography with ultraviolet detection (277 nm) and structurally elucidated by liquid chromatography with mass spectrometry. With acetonitrile/5 mmol/L ammonium acetate solution as the eluent and 1 mL/min as the flow rate on a C18 column, the derivatives were eluted at 10.6 and 14.8 min. Good linearity (correlation coefficients > 0.999) and low limits of quantitation (0.6 ppm) were obtained. The recoveries were in the range of 80-115% with relative standard deviation < 5.0%. Finally, the established method was successfully used for the determination of methyl methanesulfonate and ethyl methanesulfonate in methanesulfonic acid.
甲磺酸在制药中经常使用，但可能含有潜在的遗传毒性杂质，如甲基甲磺酸酯和乙基甲磺酸酯。本研究旨在开发一种简单的高效液相色谱法，结合紫外检测法，用于测定甲磺酸中的甲基甲磺酸酯和乙基甲磺酸酯。将水/乙腈（200 μL）中的样品（250 mg）与 10.0 mol/L 氢氧化钠溶液（270 μL）混合。然后，将其与 2.0 mg/mL N，N-二乙基二硫代氨基甲酸盐（500 μL）混合，用 N，N-二甲基乙酰胺稀释至 5 mL，并在 80°C 下反应 1 小时。用梯度高效液相色谱法，结合紫外检测（277 nm）分析衍生物，并通过液相色谱法结合质谱进行结构鉴定。以乙腈/5 mmol/L 乙酸铵溶液为洗脱液，流速为 1 mL/min，在 C18 柱上，衍生物在 10.6 和 14.8 min 洗脱。获得了良好的线性（相关系数>0.999）和低定量下限（0.6 ppm）。回收率在 80-115%之间，相对标准偏差<5.0%。最后，该方法成功地用于测定甲磺酸中的甲基甲磺酸酯和乙基甲磺酸酯。
