The Second International Standard for Oxytetracycline

Abstract

The National Institute for Medical Research, London, was requested by the WHO Expert Committee on Biological Standardization to establish a second International Standard for Oxytetracycline, since stocks of the first International Standard were depleted. A batch of 500 g of oxytetracycline dihydrate obtained in 1963 was distributed into ampoules in 125-mg amounts; the ampoules were filled with dried nitrogen and sealed. The usual procedure of exhaustively drying the material was omitted since removal of water of hydration adversely affects stability of oxytetracycline dihydrate. The proposed replacement material has been assayed biologically in terms of the first International Standard in 9 laboratories in 7 countries by means of plate-diffusion and turbidimetric assays.

Significant heterogeneity of the potencies obtained by the different laboratories and within 3 laboratories was not attributable to any known differences in assay technique; the weighted mean potencies obtained by all laboratories were within a range of ±2% of the over-all mean potency.

The potency of the second International Standard is approximately 3% less than that of the first International Standard but no significant difference in composition or purity could be detected by a variety of chemical and physical analytical methods. The material has been established as the second International Standard for Oxytetracycline with a defined potency of 880 IU/mg. The International Unit of Oxytetracycline is defined as the activity of 0.0011364 mg of the second International Standard of Oxytetracycline.

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