Ceftazidime 潛在不純物之鑑定、合成與光譜特性   全文下載

Identification, Synthesis and Spectral Characterization of a Potential Impurity of Ceftazidime

Ceftazidime研發過程中，經由簡單的高效液相層析，發現超過限量0.1%之不純物。以液相層析質譜儀測定其分子量外，為瞭解其特性，合成並純化該物質，經高效液相層析比對，合成之不純物與Ceftazidime含不純物樣本的滯留時間一致。經紅外線、質譜儀、核磁共振等光譜技術確證該不純物的結構式，係Ceftazidime結構中羧酸的甲酯化產物，分子式為C23H24N6O7S2，分子量560。

During the process development of ceftazidime, a new impurity which exceeded the limit of 0.1% was detected by a simple HPLC method. The molecular weight of the target impurity was determined by LC/MS. This suspected impurity was synthesized and purified for characterization. When co-injected with ceftazidime in HPLC, the retention time of the impurity was the same as the ceftazidime sample containing the impurity. The structural determination of the suspected impurity was conducted by IR, MS, 1H-NMR and 13C-NMR spectroscopic techniques. This new impurity was the methyl ester of ceftazi-dime, and its structure was determined as (6R,7R)-7-[[(Z)-2-(2-aminothiazol-4-yl)-2-[(1-methoxycarbonyl-1-methylethoxy) imino]acetyl]amino]-8-oxo-3-[(1-pyridinio)methyl]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate, with molecular formula of C23H24N6O7S2 and molecular weight of 560 Da.