Reduced solubility of short-acting soluble insulins when mixed with longer-acting insulins

Using insulins from three manufacturers, we examined the recovery by radioimmunoassay of short-acting soluble insulin when mixed with long-acting insulin as a function of the ratio of the mixture and the time of pre-mixing. In ratios of 1:2, 1:3, and 1:5 (short- to long-acting insulin), all Novo, Nordisk, and Lilly short-acting insulins tested showed a significant loss of solubility when mixed with the respective company's long-acting insulin either for less than 75 s or for 20 min before centrifugation. In ratios of 1:1, Novo's Actrapid (regular) with Monotard (lente) and Lilly's regular with lente showed no significant loss of solubility when pre-mixed for less than 75 s, and the regular insulin also showed no significant loss when pre-mixed for 20 min. However, when Lilly's regular was mixed with either NPH or ultralente in a 1:1 ratio, a significant loss of solubility of the short-acting insulin occurred regardless of time [as was also found with Nordisk's Velosulin (regular) with insulatard (NPH)]. When Lilly regular was incubated with Lilly lente in ratios of 1:3 for less than 75 s, 20 min, 4 h, and 24 h before centrifugation, there was a progressive loss of solubility. In contrast, with the same ratios and times of pre-mixing, Lilly regular when mixed with Lilly NPH showed a rapid initial loss of solubility that plateaued by 20 min before centrifugation.(ABSTRACT TRUNCATED AT 250 WORDS)