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Development of trace analysis for alkyl methanesulfonates in the delgocitinib drug substance using GC-FID and liquid–liquid extraction with ionic liquid
Open Chemistry ( IF 2.1 ) Pub Date : 2020-08-11 , DOI: 10.1515/chem-2020-0093
Shinkichi Nomura 1, 2 , Yoshiharu Ito 1 , Shigehiko Takegami 2 , Tatsuya Kitade 2
Affiliation  

Abstract Alkyl methanesulfonates are genotoxic impurities that should be limited to an intake of not more than 1.5 µg/day, as regulated by the International Council for Harmonization guideline M7. We herein report a trace analysis of methyl methanesulfonate (MMS), ethyl methanesulfonate (EMS), and isopropyl methanesulfonate (IPMS) in the delgocitinib drug substance using liquid–liquid extraction, with an ionic liquid as the sample-solving medium, and direct injection gas chromatography detected with a flame-ionization detector. The proposed method takes advantage of the fine solubility of ionic liquids toward the drug substance, the good extraction efficiency of alkyl methanesulfonates in liquid–liquid extraction using the Chem Elut cartridge with low-polar organic solvents, and the ability of alkyl methanesulfonates to concentrate in minimum amounts of organic solvent, resulting in excellent sensitivity and selectivity. Specifically, for the preparation of the sample solution, a mixture of 1-butyl-3-methylimidazolium chloride, water, and acetonitrile was used as the sample-solving media, extracted with diethyl ether, and the eluent was concentrated to 1 mL. The method showed good linearity, accuracy, and precision from 1 to 5 ppm, and the limits of detection of MMS, EMS, and IPMS were 0.1, 0.05, and 0.05 ppm, respectively.

中文翻译:

使用 GC-FID 和离子液体液-液萃取对 delgocitinib 原料药中的烷基甲磺酸盐进行痕量分析

摘要 烷基甲磺酸盐是遗传毒性杂质,根据国际协调委员会指南 M7 的规定,其摄入量应限制在不超过 1.5 µg/天。我们在此报告了使用液-液萃取法,以离子液体为样品溶解介质,并直接注射对 delgocitinib 原料药中的甲磺酸甲酯 (MMS)、甲磺酸乙酯 (EMS) 和甲磺酸异丙酯 (IPMS) 进行痕量分析气相色谱仪用火焰离子化检测器检测。所提出的方法利用了离子液体对药物物质的良好溶解性,以及在使用 Chem Elut 小柱和低极性有机溶剂的液-液萃取中烷基甲磺酸盐的良好萃取效率,以及甲磺酸烷基酯在最少量的有机溶剂中浓缩的能力,从而产生出色的灵敏度和选择性。具体地,在制备样品溶液时,以氯化1-丁基-3-甲基咪唑鎓、水和乙腈的混合物作为样品溶解介质,用乙醚萃取,并将洗脱液浓缩至1mL。该方法在 1 至 5 ppm 范围内表现出良好的线性、准确度和精密度,MMS、EMS 和 IPMS 的检出限分别为 0.1、0.05 和 0.05 ppm。并将洗脱液浓缩至 1 mL。该方法在 1 至 5 ppm 范围内表现出良好的线性、准确度和精密度,MMS、EMS 和 IPMS 的检出限分别为 0.1、0.05 和 0.05 ppm。并将洗脱液浓缩至 1 mL。该方法在 1 至 5 ppm 范围内表现出良好的线性、准确度和精密度,MMS、EMS 和 IPMS 的检出限分别为 0.1、0.05 和 0.05 ppm。
更新日期:2020-08-11
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