STABILITY OF INSULIN LISPRO IN INSULIN INFUSION SYSTEMS

OBJECTIVE -- To test stability of insulin lispro in two insulin infusi on systems over 48 h. RESEARCH DESIGN AND METHODS -- We used reverse-p hase and size-exclusion high-performance liquid chromatography (HPLC) to determine the purity, potency, and degree of polymerization of U100 insulin lispro (Humalog) after 24- and 48-h pump cycles conducted at 37 degrees in five Disetronic H-TRON V100 and five MiniMed 504 pumps. Pumps were set to deliver a basal rate of 0.5 U/h and 6-U boluses at t = 0, 4, 8, 24, 24.5, 28.5, 32.5, and 48 h during each cycle. The effl uent was collected into l-ml vials, pooled at 24 or 48 h, and stored a t 4 degrees C until assay After each 48-h run period of insulin delive ry, assays for potency, polymer and purity were performed on the poole d samples from each individual cycle. m-cresol content and the pooled reservoir content were assayed in the 48-h pooled samples. RESULTS -- Insulin lispro retained full HPLC potency (Delta less than or equal to 4%) at 48 h, with no degradation of insulin lispro to des-amidoinsuli n forms (24 or 48 h). No increase in pumped insulin polymer concentrat ion was observed following 24 h of pump flow Nonsignificant increases of less than or equal to 0.09% (Disetronic) and less than or equal to 0.15% (MiniMed) from initial concentrations of 0.18% (polymer divided by total insulin) were detected in three of five pump cycles at 48 h w hen compared with 37 degrees C paired controls. Nonsignificant decreas es (<5 and 10%, Disetronic and MiniMed, respectively) of m-cresol cont ent occurred in both systems following 48 h storage in each device, bu t sterility was not compromised by this decrease (initial m-cresol con centration, 3.15 mg/ml). Pump performance was without mechanical or el ectrical fault throughout the study. Basal and bolus insulin delivery was evaluated three times daily and remained as expected. Occlusion of catheters by insulin precipitation did not occur, and no change in pH was observed following delivery. CONCLUSIONS -- We conclude that insu lin lispro is suitable for prolonged infusion in these two medical dev ices when syringes and catheters are replaced at 48-h intervals.