Wienen Frank, Holzgrabe Ulrike
Institute of Pharmacy and Food Chemistry, University of Würzburg,Würzburg, Germany.
Electrophoresis. 2003 Sep;24(17):2948-57. doi: 10.1002/elps.200305529.
Aminoglycoside antibiotics are always a mixture of structurally related amino sugars, which do not have a chromophore or fluorophore. The aim of the study was to find one method for evaluation of the components and impurities of the antibiotics. Derivatization with o-phthaldialdehyde and thioglycolic acid is found to be appropriate for all antibiotics. The components of gentamicin (GM), sisomicin, netilmicin, kanamycin, amikacin, and tobramycin were tried to separate by means of micellar electrokinetic chromatography. The background electrolyte was composed of sodium tetraborate (100 mM, pH 10.0), sodium deoxycholate (20 mM), and beta-cyclodextrin (15 mM). This method is valid for evaluation of GM, kanamycin, and tobramycin. It has to be improved for amikacin and netilmicin. In addition, 46 bulk samples of GM of different manufacturer or pharmaceutical companies were investigated. Many samples were found to contain many minor products and different amounts. Beside different patterns of the main compounds GM C1, GM C1a, GM C2a, and GM C2, many lots were found consisting of a substantial number of minor products. The appearance of a high number of minor products is always associated with the existence of sisomicin, which is not found in "pure" samples. However, almost all samples met the requirements of the European Pharmacopoeia (EP) and United States Pharmacopoeia (USP).
氨基糖苷类抗生素总是结构相关的氨基糖的混合物，这些氨基糖没有发色团或荧光团。本研究的目的是找到一种评估抗生素成分和杂质的方法。发现用邻苯二甲醛和巯基乙酸进行衍生化适用于所有抗生素。尝试通过胶束电动色谱法分离庆大霉素（GM）、西索米星、奈替米星、卡那霉素、阿米卡星和妥布霉素的成分。背景电解质由硼酸钠（100 mM，pH 10.0）、脱氧胆酸钠（20 mM）和β-环糊精（15 mM）组成。该方法对GM、卡那霉素和妥布霉素的评估有效。对阿米卡星和奈替米星则有待改进。此外，还对46个来自不同生产商或制药公司的GM原料药样品进行了研究。发现许多样品含有许多次要产物且含量不同。除了主要化合物GM C1、GM C1a、GM C2a和GM C2的不同模式外，还发现许多批次含有大量次要产物。大量次要产物的出现总是与西索米星的存在有关，而在“纯”样品中未发现西索米星。然而，几乎所有样品都符合欧洲药典（EP）和美国药典（USP）的要求。
