Loseva G I, Snezhnova L P, Shatrova V M, Zak A F
Antibiotiki. 1978 Apr;23(4):313-7.
The content of admixtures in tetracycline stored under different conditions was determined with chromatographic and spectrophotometric methods. Biological activity, toxicity and colour of the drugs was tested. The changes in teh colour of tetracycline most pronounced on its storage at a temperature of 37 degrees C and elevated humidity were not accompanied by an increase in the content of anhydrotetracyclines. In parallel with the changes in the colour of tetracycline, the loss of its biological activity up to 30 per cent and increased toxicity were registered. The LD50 decreased by 40 per cent as compared to the initial level. Simultaneously an additional spot with high chromatographic mobility (Rf 0.98--1.0) was detected on thin-layer chromatograms. It was shown that the processes of tetracycline degradation resulting in marked darkening of the drug colour were not accompanied by an increase in the content of anhydro admixtures. They were probably the result of accumulation of other products which are as highly toxic and low active as the anhydroderivatives of tetracycline.
采用色谱法和分光光度法测定了在不同条件下储存的四环素中杂质的含量。对药物的生物活性、毒性和颜色进行了测试。四环素在37℃和高湿度条件下储存时颜色变化最为明显,但脱水四环素的含量并未增加。与四环素颜色变化同时,其生物活性损失高达30%,毒性增加。与初始水平相比,半数致死量(LD50)降低了40%。同时,在薄层色谱图上检测到一个具有高色谱迁移率(比移值Rf为0.98 - 1.0)的额外斑点。结果表明,导致药物颜色明显变深的四环素降解过程并未伴随脱水杂质含量的增加。它们可能是其他产物积累的结果,这些产物与四环素的脱水衍生物一样具有高毒性和低活性。