Sulfonate esters have been recognized as potential genotoxic impurities (PGIs) in pharmaceuticals. An LC-MS/MS method was developed and validated for the simultaneous determination of 15 sulfonate esters, including methyl, ethyl, propyl, isopropyl, and n-butyl esters of methanesulfonate, benzenesulfonate, and p-toluenesulfonate in drug products. The method utilized atmospheric pressure chemical ionization (APCI) in multiple reaction monitoring (MRM) mode for the quantitation of impurities. The method employed an ODS column as the stationary phase and water-acetonitrile as the solvents for gradient elution without derivatization steps. The method was specific, linear, accurate, precise, and robust. Recoveries of the sulfonic esters from three drug matrices were observed in the range of 91.6∼109.0% with an RSD of not greater than 17.9% at the concentration of the LOQ and in the range of 90.4%∼105.2% with an RSD of not greater than 7.1% at the concentration of 50 ng/mL for the methanesulfonates and 10 ng/mL for the benzenesulfonates and p-toluenesulfonates. The LOD was not greater than 15 ng/mL, 2 ng/mL, and 1 ng/mL for the methanesulfonate, benzenesulfonate, and p-toluenesulfonate esters, respectively. This method was sufficiently sensitive to detect the 15 PGIs in the phentolamine mesylate tablet, amlodipine besylate tablet, and tosufloxacin tosylate tablet. This analytical method is a direct, specific, rapid, and accurate quality control tool for the determination of the 15 sulfonate esters that are most likely to exist in drug products.

中文翻译：

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通过LC-APCI-MS / MS同时测定甲磺酸苯酚酚胺，苯磺酸氨氯地平和甲苯磺酸甲苯磺沙星中15种磺酸酯的杂质。

磺酸酯已被认为是药物中潜在的遗传毒性杂质（PGI）。已开发出LC-MS / MS方法并经过验证，可同时测定15种磺酸酯，包括药品中甲磺酸酯，苯磺酸酯和对甲苯磺酸酯的甲酯，乙酯，丙酯，异丙酯和正丁酯。该方法利用多反应监测（MRM）模式下的常压化学电离（APCI）进行杂质定量。该方法采用ODS色谱柱作为固定相，采用水-乙腈作为溶剂进行梯度洗脱，无需衍生化步骤。该方法特异，线性，准确，精确且可靠。从三种药物基质中回收的磺酸酯的回收率在91.6％至109.0％之间，RSD不大于17。LOQ浓度为9％，在90.4％〜105.2％范围内，甲磺酸盐为50 ng / mL，苯磺酸盐和对甲苯磺酸盐为10 ng / mL时，相对标准偏差不大于7.1％。 。甲磺酸酯，苯磺酸酯和对甲苯磺酸酯的LOD分别不大于15 ng / mL，2 ng / mL和1 ng / mL。此方法足够灵敏，足以检测甲磺酸苯妥拉明片剂，苯磺酸氨氯地平片剂和甲苯磺酸托沙沙星片剂中的15种PGI。这种分析方法是直接，特定，快速和准确的质量控制工具，用于确定最有可能存在于药品中的15种磺酸酯。甲磺酸盐浓度为50 ng / mL，浓度为1％，苯磺酸盐和对甲苯磺酸盐浓度为10 ng / mL。甲磺酸酯，苯磺酸酯和对甲苯磺酸酯的LOD分别不大于15 ng / mL，2 ng / mL和1 ng / mL。此方法足够灵敏，足以检测甲磺酸苯妥拉明片剂，苯磺酸氨氯地平片剂和甲苯磺酸妥苏沙星片剂中的15种PGI。这种分析方法是直接，特定，快速和准确的质量控制工具，用于确定最有可能存在于药品中的15种磺酸酯。甲磺酸盐浓度为50 ng / mL，浓度为1％，苯磺酸盐和对甲苯磺酸盐浓度为10 ng / mL。甲磺酸酯，苯磺酸酯和对甲苯磺酸酯的LOD分别不大于15 ng / mL，2 ng / mL和1 ng / mL。此方法足够灵敏，足以检测甲磺酸苯妥拉明片剂，苯磺酸氨氯地平片剂和甲苯磺酸妥苏沙星片剂中的15种PGI。这种分析方法是直接，特定，快速和准确的质量控制工具，用于确定最有可能存在于药品中的15种磺酸酯。此方法足够灵敏，足以检测甲磺酸苯妥拉明片剂，苯磺酸氨氯地平片剂和甲苯磺酸托沙沙星片剂中的15种PGI。这种分析方法是直接，特定，快速和准确的质量控制工具，用于确定最有可能存在于药品中的15种磺酸酯。此方法足够灵敏，足以检测甲磺酸苯妥拉明片剂，苯磺酸氨氯地平片剂和甲苯磺酸妥苏沙星片剂中的15种PGI。这种分析方法是直接，特定，快速和准确的质量控制工具，用于确定最有可能存在于药品中的15种磺酸酯。