柱切换在线除盐DGLC-MS联用鉴定克林霉素磷酸酯中杂质  

Identification of impurities in clindamycin phosphate by column-switching and online demineralization technique for dual gradient liquid chromatography combined with mass spectrometry

作　　者：刘珊[1] 陈悦 洪利娅[1,2] 曾明飞 刘绿叶 

机构地区：[1]浙江工业大学,杭州310014 [2]浙江省食品药品检验研究院,杭州310004 [3]赛默飞世尔科技(中国)有限公司,上海200210

出　　处：《中国抗生素杂志》2014年第9期669-674,692,共7页Chinese Journal of Antibiotics

基　　金：浙江海翔药业股份有限公司

摘　　要：目的利用柱切换在线除盐DGLC-MS联用鉴定克林霉素磷酸酯中的杂质。方法采用Thermo Ultimate 3000二维色谱DGLC(双三元泵液相)系统串联TSQ Vantage MS正负离子同时扫描测定:左泵,一维分析柱Acclaim C18柱(150mm×4.6mm,5μm),含非挥发性盐流动相,流速1.1m L/min;右泵,二维分析柱Acclaim PA2柱(3.0mm×50mm,3μm),含挥发性盐溶液流动相,流速0.3m L/min;柱温:30℃;进样量:20μL;检测波长:210nm。结果在不改变克林霉素磷酸酯国家药典方法的前提下,通过柱切换在线除盐技术使得分析条件能够兼容质谱并鉴定出克林霉素磷酸酯中9种杂质,其中一种新杂质分子量为504。结论该方法巧妙地解决了液相条件和液质联用仪不兼容的难题,并具有稳定性、重现性、可追溯性的优点,值得推广应用。Objective To identify impurities in clindamycin phosphate by column-switching and online demineralization technique for DGLC （dual gradient high-performance liquid chromatography） combined with TSQ Vantage triple-quadrupole mass spectrometry. Methods Thermo Ultimate 3000 DGLC Combined with TSQ Vantage MS was scanning in positive and negative ions mode at the same time. 1-dimensional analytical column was Acclaim C18 column（150mm×4.6mm, 5μm）with non-volatile salt mobile phase at the flow rate of 1.1mL/min（left pump）,2- dimensional analytical column was Acclaim PA2 column （3.0 mm×50mm, 3μm） with volatile salt mobile phase at the flow rate of 0.3mL/min（right pump）; The column temperature was at 30℃, and the injection volume was 20μL; The detection wavelength was 210nm. Results The column-switching and online demineralization technique made the condition in pharmaco-poeia monography of clindamycin phosphate could be compatible with mass spectrometry with-out any change; Nine impurities of clindamycin phosphate were identified and a new impurity with relative molecular mass of 504 was found. Conclusions The method masterly solved the problem of incompatibility between non-volatile salt mobile phase and mass spectrometry, it was also worthy of popularization and application with the advantages of stability, repeatability and traceability.

关 键 词：克林霉素磷酸酯 杂质 柱切换 在线除盐 DGLC—MS 

分 类 号：R978.1[医药卫生—药品]