Stability of the 4th International Standard for Insulin

Abstract

Summary. The stability of the (W.H.O.) 4th InternationalStandard for Insulin, has been assessed by accelerated thermal degradation studies. This is a crystalline preparation of insulin, freed from proteolytic enzymes, sealed in ampoules containing air and with a moisture content of 5-6%. Of the original biological activity 95.8 (92.8-98.9; P = 0.95)% was retained after storage for 12 years in the dark at 20 ~ C and 65.7 (63.4-68.1; P= 0.95)% after 14 years at 37 ~ C. Degradation rate constants were calculated from these data for the Standard at 20 ~ C and 37 ~ C, assuming first order kinetics. The degradation constant at 37~ did not differ significantly from those found in earlier degradation studies at 37~ over shorter periods, thereby supporting the assumption that the degradation of crystalline insulin, at least at 37 ~ C, is a first order reaction. Extrapolation of these data suggests that the Standard stored at -20~ for 20 years would have retained at least 99.93% (P = 0.95) of its original activity and so for practical purposes can be considered to be stable.

Stability of the Third International Standard for Corticotrophin: Accelerated Degradation Study Using Different Bioassays and Isoelectric Focusing

“…However, first order kinetics have been shown to describe data obtained from degradation studies of other polypeptide hormone standards for example insulin (Storring, Greaves, Mussett & Bangham, 1975) and thyroid-stimulating hormone (Cotes, Gaines-Das, Kirkwood, Bennie & Hunter, 1978). The combined results for all bioassays give a predicted half-life for the activity of the IS of 2800 years with an approximate lower 95% confidence limit of 500 years; the predicted activity of the IS remaining after 20 years at -20°C is 99-5% of the original activity with an approximate lower 95% confidence limit of 97-3%.…”