衍生化结合LC-MS法测定硝酸硫康唑中2种基因毒性杂质

摘要针对硝酸硫康唑中硫酸烷基酯类基因毒性杂质(包括硫酸二甲酯、硫酸二乙酯),开发了方法进行检测。HILIC色谱柱(2.1 mm×50 mm,3 μm),水相为20 mmol·L^-1甲酸铵溶液-甲酸(1 000∶1),有机相为乙腈,水相-有机相(10∶90),流速0.2 mL·min^-1,柱温20℃;采用多反应监测(MRM)模式定量检测。探讨了温度、时间对衍生化的影响。该方法硫酸二甲酯、硫酸二乙酯线性相关系数分别为0.999 7和0.998 9,回收率分别为80.3%~102.3%、90.3%~100.0%,操作简单,满足定量分析要求。

	Service

	把本文推荐给朋友
	加入我的书架
	加入引用管理器
	Email Alert
	RSS
	作者相关文章
	郭志强
	李铁军
	孙迎基
	李佩佩
	王琦

关键词：硝酸硫康唑衍生化液质联用基因毒性杂质硫酸二甲酯硫酸二乙酯

Abstract： An analytical method was established for the determination of alkyl sulfate esters genotoxic impurities in sulconazole nitrate, including dimethyl sulfate and diethyl sulfate. The separation was performed on an HILIC column(2.1 mm×50 mm, 3 μm) utilizing the aqueous phase of 20 mmol·L^-1 ammonium formate solution-formic acid (1 000∶1) and the organic phase of acetonitrile with isocratic elution(10∶90) at the flow rate of 0.2 mL·min^-1. The column temperature was set at 20 ℃. Multiple reaction monitoring (MRM) mode was performed on quantitative determination. Effects of temperature and time for derivatization were investigated. Under the conditions, the linear correlation coefficient of dimethyl sulfate and diethyl sulfate were 0.999 7 and 0.998 9, respectively. And the recovery were 80.3%—102.3% and 90.3%—100.0%, respectively. The operation is simple and meets the requirements of quantitative analysis.

Keywords： sulconazole nitrate derivatization LC-MS genotoxic impurities dimethyl sulfate diethyl sulfate

Received 2024-05-24;

Corresponding Authors: 李铁军,高级工程师,litj@jewim.com.cn Email: litj@jewim.com.cn

About author: 郭志强(1977—),男,博士,高级工程师,现从事药品质量研究方面的研究。

引用本文:

郭志强, 李铁军, 孙迎基, 李佩佩, 王琦.衍生化结合LC-MS法测定硝酸硫康唑中2种基因毒性杂质[J]. 化学工业与工程, 2025,42(1): 106-112

GUO Zhiqiang, LI Tiejun, SUN Yingji, LI Peipei, WANG Qi.Determination of two genotoxic impurities in sulconazole nitrate by combining derivatization with LC-MS method[J]. Chemcial Industry and Engineering, 2025,42(1): 106-112

[1] 许玉成.硝酸硫康唑(Sulconazole Nitrate)[J].国外医药.合成药.生化药.制剂分册,1987(3):173-174
[2] 王美芳, 李邻峰, 程海燕, 等. 1%硝酸硫康唑喷雾剂治疗足癣及鞋袜用药对预防复发的作用[J]. 中国真菌学杂志, 2018, 13(3): 164-167 WANG Meifang, LI Linfeng, CHENG Haiyan, et al. Efficacy of 1% sulconazole nitrate spray in the treatment of tinea pedis and preventive effect of spraying the shoes and socks[J]. Chinese Journal of Mycology, 2018, 13(3): 164-167(in Chinese)
[3] 刘咏梅,陆强. 3例职业性急性硫酸二甲酯中毒临床特点分析[J].中国工业医学杂志,2024,37(1):53-55
[4] 根加甫·阿尔布斯力, 石梦迪, 戴平, 等. 硫酸二甲酯致背部皮肤灼伤1例报道[J]. 中国工业医学杂志, 2023, 36(5): 417-418 GENJIAPU Aerbusili, SHI Mengdi, DAI Ping, et al. A case report of skin burn in back caused by dimethyl sulfate[J]. Chinese Journal of Industrial Medicine, 2023, 36(5): 417-418(in Chinese)
[5] 冯萌萌, 王虹, 陈佩瑾. 气相色谱-质谱法测定土壤中硫酸二甲酯和硫酸二乙酯的残留量[J]. 广东化工, 2020, 47(9): 186-187, 185 FENG Mengmeng, WANG Hong, CHEN Peijin. Determination of dimethyl sulfate and diethyl sulfate residues in soil by gas chromatography-mass spectrometry[J]. Guangdong Chemical Industry, 2020, 47(9): 186-187, 185(in Chinese)
[6] International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use(ICH). Assessment and Control of DNA Reactive (Mutagenic) Impurities in Pharmaceuticals to Limit Potentical Carcinogenic Risk M7(R1). 2015
[7] 李栋,赵海英. 9例急性硫酸二甲酯中毒护理体会[J].中国工业医学杂志,2022,35(1):91-95
[8] 汪生, 倪悦泠, 陆宇婷, 等. 顶空气相色谱法测定塞来昔布中硫酸二乙酯基因毒性杂质[J]. 中国新药杂志, 2018, 27(20): 2437-2441 WANG Sheng, NI Yueling, LU Yuting, et al. Determination of the diethyl sulphate genotoxic impurity in celecoxib by headspace gas chromatography[J]. Chinese Journal of New Drugs, 2018, 27(20): 2437-2441(in Chinese)
[9] 李一婧,张婷婷,李彤,等.气相色谱火焰光度法检测TBI-166中硫酸二甲酯和硫酸二乙酯残留量[J].药物分析杂志,2016,36(10):1847-1851
[10] 吴楚森, 王斌, 王莉, 等. 气相色谱-质谱联用测定化妆品中硫酸二甲酯与硫酸二乙酯[J]. 分析测试学报, 2018, 37(1): 70-75 WU Chusen, WANG Bin, WANG Li, et al. Determination of dimethyl sulfate and diethyl sulfate in cosmetics by GC-MS[J]. Journal of Instrumental Analysis, 2018, 37(1): 70-75(in Chinese)
[11] 毕富春, 吴国旭. 44种有机磷杀虫剂的气相色谱分析[J]. 化学工业与工程, 2001, 18(3): 156-160 BI Fuchun, WU Guoxu. Gas chromatography of 44 organophosphorus insecticides[J]. Chemical Industry and Engineering, 2001, 18(3): 156-160(in Chinese)
[12] 张韻慧, 吴金国, 张雅慧, 等. 毛细管气相色谱法测定强心滴丸中的冰片含量[J]. 化学工业与工程, 2007, 24(3): 215-217, 271 ZHANG Yunhui, WU Jinguo, ZHANG Yahui, et al. Quantitative determination of borneol in Qiangxin dripping pills by capillary gas chromatography[J]. Chemical Industry and Engineering, 2007, 24(3): 215-217, 271(in Chinese)
[13] 袁玉兵, 樊顺东, 梁花. GC-MS法测定纺织品中硫酸二乙酯的方法研究[J]. 中国纤检, 2023(8): 70-72 YUAN Yubing, FAN Shundong, LIANG Hua. Study on determination of diethyl sulfate in textiles by GC-MS[J]. China Fiber Inspection, 2023(8): 70-72(in Chinese)
[14] 鲍美玲, 陈海霞, 秦琴, 等. GC-MS法同时测定9-氨基米诺环素盐酸盐中的硫酸二甲酯和硫酸二异丙酯[J]. 海峡药学, 2018, 30(9): 51-53 BAO Meiling, CHEN Haixia, QIN Qin, et al. Simultaneous determination of dimethyl sulfate and diisopropyl sulfate in 9-amino minocycline hydrochloride by GC-MS[J]. Strait Pharmaceutical Journal, 2018, 30(9): 51-53(in Chinese)
[15] 吴健华. 硫酸二甲酯检验方法研究及化工分析难题的应对策略[J]. 化工设计通讯, 2022, 48(11): 100-102 WU Jianhua. Research on dimethyl sulfate inspection method and coping strategies for difficult problems in chemical analysis[J]. Chemical Engineering Design Communications, 2022, 48(11): 100-102(in Chinese)
[16] ALZAGA R, RYAN R W, TAYLOR-WORTH K, et al. A generic approach for the determination of residues of alkylating agents in active pharmaceutical ingredients by in situ derivatization-headspace-gas chromatography-mass spectrometry[J]. Journal of Pharmaceutical and Biomedical Analysis, 2007, 45(3): 472-479
[17] 杨亚琴, 李圆圆, 曹秀, 等. 衍生化-气相色谱法测定谷物籽粒中三氯吡氧乙酸残留量[J]. 农药, 2024, 63(3): 191-195, 227 YANG Yaqin, LI Yuanyuan, CAO Xiu, et al. Determination of triclopyr residue in cereal seeds by gas chromatography with derivatization[J]. Agrochemicals, 2024, 63(3): 191-195, 227(in Chinese)
[18] 戴琛, 汪瑾, 卢亚萍. 衍生化UPLC-MS法测定酸性植物激素[J]. 植物学报, 2022, 57(4): 500-507 DAI Chen, WANG Jin, LU Yaping. Determination of acidic plant hormones by derivative UPLC-MS[J]. Chinese Bulletin of Botany, 2022, 57(4): 500-507(in Chinese)
[19] 汪建飞, 索绪斌, 张涵. 衍生化法测定γ-氨基丁酸的含量及稳定性研究[J]. 化学研究与应用, 2022, 34(4): 909-914 WANG Jianfei, SUO Xubin, ZHANG Han. Determination and stability of γ-aminobutyric acid by derivatization[J]. Chemical Research and Application, 2022, 34(4): 909-914(in Chinese)
[20] 石蕾, 李伟松, 师浩淳, 等. 草酸二甲酯和草酸的反相高效液相色谱分析[J]. 化学工业与工程, 2016, 33(2): 91-95 SHI Lei, LI Weisong, SHI Haochun, et al. Determination of dimethyl oxalate and oxalic acid by reversed-phase high performance liquid chromatography[J]. Chemical Industry and Engineering, 2016, 33(2): 91-95(in Chinese)
[21] 王林, 吴佳豪, 许凌. 溶剂解吸-高效液相色谱法测定染料车间空气中的硫酸二甲酯[J]. 预防医学情报杂志, 2023, 39(6): 698-703 WANG Lin, WU Jiahao, XU Ling. Determination by solvent desorption-high performance liquid chromatography dimethyl sulfate in the air of dye workshop[J]. Journal of Preventive Medicine Information, 2023, 39(6): 698-703(in Chinese)
[22] 李晶,张琦,刘净. 气质联用和液质联用在农药残留检测中的运用[J].食品安全导刊,2022,(18):165-167, 171