Extremely long time stability study of selected antibiotic standards.

ABSTRACT

A study was conducted to investigate the quality of reference substances which were produced long before the introduction of advanced analysis and purification techniques. The quality and antimicrobial activity of WHO and EP oxytetracycline, doxycycline, colistin and spiramycin reference standards were assessed. The oldest substance was stored for 54 years in a freezer. Assay and purity tests were conducted according to Ph. Eur. 6.0. Additionally, antibacterial activity was tested with the microbiological method according to Ph. Eur. 4.0 (agar diffusion method). The results of the study show that several of the tested substances remained stable for over 40 years and one for over 50 years of storage. In most cases, the determined potency is close to the declared one, regardless of the method used (HPLC or microbiological). Composition analysis of multi-substance antibiotics (colistin and spiramycin) showed important differences compared with new reference substances. Results also indicate that no excessive degradation occurred during the entire storage period and impurity levels have not changed significantly.