Factors Influencing the Stabiljty of Insulin

Before any given lot of insulin can be marketed, its potency and stability must meet certain requirements. Stability is arbitrarily determined by subjecting a sample of insulin to a “heat test.” This test consists of exposing the carefully standardized insulin to a temperature of 52” for 10 days. The potency of the “heated” material is then compared either with a standard insulin or with a sample of the same preparation not exposed to the heat test. As a rule insulin thus treated loses some of its physiologic activity, but if there should be a considerable loss, e.g. 15 per cent or more, then such a preparation is not considered suitable for general use. The purpose of the heat test is to insure all insulin preparations for stability under adverse conditions. The causes of the loss of potency of the “heated” insulin have not, hitherto, been established. Traces of certain metals, particularly copper and iron, were found in some of the unstable preparations; it was therefore assumed that the presence of these metals might be a factor affecting deterioration either upon prolonged standing at room temperature or upon subjection to a heat test. The deterioration of insulin upon standing is a problem of considerable importance not only to the manufacturer but to the physician, and in particular, to the diabetic patient. Thus it was deemed advisable to secure data on this problem. For this purpose it was considered desirable to study a preparation of insulin low in its ash content and practically free of such metals as copper, iron, and zinc. This paper deals with (1) a method for the preparation of an insulin low in ash and free of copper, iron, and zinc; (2) the effect of temperature on the stability of such a preparation; and (3)