Lougheed W D, Zinman B, Strack T R, Janis L J, Weymouth A B, Bernstein E A, Korbas A M, Frank B H
LTBO (Loyal True Blue & Orange) Research Institute, Richmond Hill, Ontario, Canada.
Diabetes Care. 1997 Jul;20(7):1061-5. doi: 10.2337/diacare.20.7.1061.
To test stability of insulin lispro in two insulin infusion systems over 48 h.
We used reverse-phase 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 C 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 effluent was collected into 1-ml vials, pooled at 24 or 48 h, and stored at 4 degrees C until assay. After each 48-h run period of insulin delivery, assays for potency, polymer, and purity were performed on the pooled samples from each individual cycle. m-cresol content and the pooled reservoir content were assayed in the 48-h pooled samples.
Insulin lispro retained full HPLC potency (delta < or = 4%) at 48 h, with no degradation of insulin lispro to des-amidoinsulin forms (24 or 48 h). No increase in pumped insulin polymer concentration was observed following 24 h of pump flow. Nonsignificant increases of < or =0.09% (Disetronic) and < or =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 when compared with 37 degrees C paired controls. Nonsignificant decreases (<5 and 10%, Disetronic and MiniMed, respectively) of m-cresol content occurred in both systems following 48 h storage in each device, but sterility was not compromised by this decrease (initial m-cresol concentration, 3.15 mg/ml). Pump performance was without mechanical or electrical 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.
We conclude that insulin lispro is suitable for prolonged infusion in these two medical devices when syringes and catheters are replaced at 48-h intervals.
测试赖脯胰岛素在两种胰岛素输注系统中48小时内的稳定性。
我们采用反相和尺寸排阻高效液相色谱法（HPLC），在37℃下，对5台Disetronic H-TRON V100泵和5台美敦力504泵进行24小时和48小时的泵循环后，测定优泌乐U100（Humalog）的纯度、效价和聚合度。在每个循环中，泵被设置为在t = 0、4、8、24、24.5、28.5、32.5和48小时时以0.5 U/h的基础速率和6 U的大剂量输注。流出物收集到1毫升小瓶中，在24小时或48小时时合并，并在4℃下储存直至检测。在每次48小时的胰岛素输注运行期后，对每个单独循环的合并样品进行效价、聚合物和纯度检测。在48小时的合并样品中检测间甲酚含量和合并储液器含量。
赖脯胰岛素在48小时时保持了完整的HPLC效价（δ≤4%），且赖脯胰岛素没有降解为脱酰胺胰岛素形式（24小时或48小时）。泵流动24小时后，未观察到泵入胰岛素聚合物浓度增加。与37℃配对对照相比，在48小时时，5个泵循环中的3个循环中，检测到聚合物浓度从初始浓度0.18%（聚合物除以总胰岛素）分别非显著增加≤0.09%（Disetronic）和≤0.15%（美敦力）。在每个设备中储存48小时后，两个系统中间甲酚含量均出现非显著下降（分别为Disetronic和美敦力的<5%和10%），但这种下降并未影响无菌性（初始间甲酚浓度为3.15毫克/毫升）。在整个研究过程中，泵的性能没有机械或电气故障。每天对基础和大剂量胰岛素输注进行三次评估，结果符合预期。未发生胰岛素沉淀导致的导管堵塞，输注后未观察到pH值变化。
我们得出结论，当每隔48小时更换注射器和导管时，赖脯胰岛素适用于在这两种医疗设备中进行长时间输注。
