加替沙星主要相关杂质的分离和鉴定

目的加替沙星原料药中相关杂质的分离及结构鉴定。方法用液相色谱/质谱联用技术分离并鉴定加替沙星原料中的主要相关杂质,并合成了两个化合物:1-环丙基-6-氟-8-甲氧基-7-(1-哌嗪基)-1,4-二氢-4-氧代-3-喹啉羧酸(简称DMP)和1-环丙基-6-氟-8-羟基-7-(3-甲基-1-哌嗪基)-1,4-二氢-4-氧代-3-喹啉羧酸(简称DMO)。比较合成的化合物与原料中相关杂质的液相色谱、紫外吸收光谱及质谱。结果相关杂质的分子量比加替沙星少14,即一个亚甲基,合成的DMP的液相色谱、紫外吸收光谱及质谱分析结果与原料药中相关杂质一致。结论确证了该相关杂质的结构为1-环丙基-6-氟-8-甲氧基-7-(1-哌嗪基)-1,4-二氢-4-氧代-3-喹啉羧酸。

IMPURITY ANALYSIS AND THEIR STRUCTURE DETERMINATION OF GATIFLOXACIN

AIM: To analyse the impurities of gatifloxacin. METHODS: The impurity of gatifloxacin were analysized and determinated by RP-HPLC/electrospray ionization mass spectrometry with a Zorbax SB-C18(4.6 mm x 150 mm ID, 5 microns). The mobile phase was 3% acetic acid/acetonitrile-3% acetic acid/water (15:85). The two compounds were synthesized: 1-cyclopropyl-6-fluoro-1, 4-dihydro-8-methoxy-7-(1-piperazinyl)-4-oxo-3-quinolinecarboxylic acid (DMP) and 1-cyclopropyl-6-fluoro-1, 4-dihydro-8-hydro-7-(3-methy-1-piperazinyl)-4-oxo-3-quinolinecarboxylic acid (DMO). Their liquid chromatogram, UV, MS were compared with those of the impurity of gatifloxacin. RESULTS: The mass of the impurity was 14 less than that of gatifloxacin. It means the impurity was CH2 less than gatifloxacin. The tR (HPLC), UV and MS of DMP were the same as those of the impurity of gatifloxacin. CONCLUSION: Based on the tR (HPLC), UV and MS, the impurity of gatifloxacin is confirmed as DMP.