HPLC-ESI-MSⁿ法分离和鉴定盐酸克林霉素棕榈酸酯原料药中的10种杂质

目的: 用HPLC-ESI-MSⁿ法分离和鉴定国产盐酸克林霉素棕榈酸酯原料药中的10种杂质,并探讨这些杂质的质谱裂解规律。 方法: 采用Agilent ZORBAX SB-C₈色谱柱(150 mm×3.0 mm,3.5 μm),流动相为5 mmol·L^-1醋酸铵溶液-乙腈(25:75),在正离子检测方式下,AB SCIEX 4000 Q TRAP LC/MS/MS仪对盐酸克林霉素棕榈酸酯中的杂质进行在线多级质谱分析。 结果: 通过多级质谱裂解推断盐酸克林霉素棕榈酸酯原料药中10种杂质分别为克林霉素、丙叉克林霉素、亚砜克林霉素棕榈酸酯、克林霉素十二酸酯、棕榈酸乙酯、克林霉素十四酸酯、克林霉素B棕榈酸酯、表克林霉素棕榈酸酯、克林霉素十八酸酯、丙叉克林霉素棕榈酸酯。 结论: 鉴定了盐酸克林霉素棕榈酸酯原料药中10个杂质的结构,其中3个杂质为新的杂质。

Objective: Ten impurities in clindamycin palmitate hydrochloride drug substances made in China were separated and identified by HPLC-ESI-MSⁿ method.The fragmentation patterns and structural assignment of these impurities were studied. Methods: Agilent ZORBAX SB-C₈ column(150 mm×3.0 mm,3.5 μm)was used with a mobile phase of 5 mmol·L^-1 ammonium acetate solution-acetonitrile(25:75).In positive mode,the impurities in clindamycin palmitate hydrochloride were analyzed by AB SCIEX 4000 Q TRAP LC/MS/MS.The complete fragmentation patterns of ten impurities were studied by MSⁿ and used to obtain information about the structure of these impurities. Results: The ten impurities in clindamycin palmitate hydrochloride drug substances were deduced based on the HPLC-MSⁿ data as clindamycin,anisylidene clindamycin,clindamycin palmitate sulphoxides,clindamycin laurate,ethyl palmitate,clindamycin myristate,clindamycin B-palmitate,epiclindamycin palmitate,clindamycin stearate,anisylidene clindamycin palmitate. Conclusion: The structures of ten impurities in clindamycin palmitate hydrochloride drug substances were identified,of which three impurities were new impurities.