盐酸洛美沙星光降解的部分杂质研究  

Studies on some photodegradation products of lomefloxacin hydrochloride

作　　者：李菊[1] 李晶晶[2] 黄青[2] 姚其正[1] 

机构地区：[1]中国药科大学药学院,南京210009 [2]江苏省食品药品检验所,南京210008

出　　处：《中国抗生素杂志》2012年第6期459-463,共5页Chinese Journal of Antibiotics

摘　　要：目的确定控制盐酸洛美沙星光降解杂质的必要性。方法用液相色谱/质谱联用技术分离并鉴定盐酸洛美沙星的两个光降解杂质,并化学合成了两个化合物:脱羧洛美沙星[(±)-1-乙基-6,8-二氟-1,4-二氢-7-(3-甲基-1-哌嗪基)-4-氧代喹啉(简称DCLM)]和氯代洛美沙星[(±)-1-乙基-6-氟-8-氯-1,4-二氢-7-(3-甲基-1-哌嗪基)-4-氧代喹啉-3-羧酸(简称CLLM)]。比较DCLM和CLLM与盐酸洛美沙星相应光降解杂质的液相色谱和质谱。测试洛美沙星、DCLM及CLLM体外细胞毒性。结果化学合成的DCLM和CLLM的液相色谱和质谱分析结果分别与盐酸洛美沙星相应光降解杂质一致。洛美沙星、DCLM和CLLM的IC_(50)分别为1.9mmol/L,2.2mmol/L,0.7mmol/L。结论确证了盐酸洛美沙星的两个光降解杂质分别为:DCLM和CLLM。DCLM的体外细胞毒性与洛美沙星相近;CLLM的体外细胞毒性显著强于洛美沙星,可能是导致洛美沙星临床不良反应的物质。Objective To determine the necessity of controlling the photodegradation products of lomefloxacin hydrochloride. Methods HPLC/MS was used to analyze and identify two photodegradation products of lomefloxacin hydrochloride. Two compounds were synthesized： 1-ethyl-6, 8-difluoro-7-（3-methyl-l-piperazin-yl） quinolin-4（1H）-one （DCLM） and 8-chloro-ethyl-6-fluoro-7-（3-methyl-1-piperazin-yl）-4-oxo-1,4-dihydroquinoline- 3-carboxylic acid （CLLM）. Their HPLC chromatogram and MS spectrum were compared with those of the corresponding photodegradation products. The cytotoxicity of lomefloxacin, DCLM and CLLM were tested. Results The tR（HPLC） and MS of DCLM and CLLM were the same as those of corresponding photodegradation products. The respective IC50 of lomefloxacin, DCLM and CLLM were 1.9mmol/L, 2.2mmol/L, 0.7mmol/L. Conclusion Based on the tR（HPLC） and MS, the two photodegradants of lomefloxacin hydrochloride are confirmed as DCLM and CLLM. The cytotoxicity of DCLM is similar to that of lomefloxacin. CLLM has stronger cytotoxicity, which may lead to adverse reactions in clinical.

关 键 词：洛美沙星:光降解杂质分析 液相色谱/质谱联用 毒性测试 

分 类 号：R978.19[医药卫生—药品]