Kenley R A, Tracht S, Stepanenko A, Townsend M, L'Italien J
Cabrillo Facility of Magellan Laboratories, Inc., 9250 Trade Place, San Diego, CA 92126, USA.
AAPS PharmSciTech. 2000 Mar 18;1(2):E7. doi: 10.1208/pt010207.
The stability of the 37-amino acid peptide pramlintide, in aqueous solution, was studied as a function of pH and temperature. Samples of pramlintide formulated as a parenteral product were exposed to elevated temperatures and to realistic storage conditions for as long as 30 months. Pramlintide degradation was monitored by three high-performance liquid chromatography (HPLC) methods: a reversed-phase (RP-HPLC) and a strong-cation exchange (SCX-HPLC) method for percentage purity determination by area normalization, plus a second RP-HPLC method for potency determination versus external standards. The pH-rate profile for pramlintide shows increasing degradation rate constants with increasing pH over the range pH = 3.5 to 5.0. The Arrhenius expression for pramlintide degradation at pH = 4.0 over the temperature range 5 degrees C to 50 degrees C is ln(k(0))= 37.39-21.900/RT, where k(0) is the zero-order rate constant (in %/mo) for pramlintide degradation. The pramlintide parenteral product formulated at pH = 4.0 is extremely stable, with percentage purity and percentage potency loss of only approximately 2% over 30 months at 5 degrees C. The formulated pramlintide drug product has acceptable shelf life for long-term storage at 5 degrees C and up to a 30-day patient use when stored at ambient temperature.
研究了含37个氨基酸的普兰林肽在水溶液中的稳定性与pH值和温度的关系。将制成注射用产品的普兰林肽样品置于高温及实际储存条件下长达30个月。采用三种高效液相色谱（HPLC）方法监测普兰林肽的降解情况：一种反相（RP-HPLC）和一种强阳离子交换（SCX-HPLC）方法，通过面积归一化法测定纯度百分比，另一种RP-HPLC方法用于相对于外标物测定效价。普兰林肽的pH-速率曲线显示，在pH = 3.5至5.0范围内，随着pH值升高，降解速率常数增加。在5℃至50℃温度范围内，pH = 4.0时普兰林肽降解的阿伦尼乌斯表达式为ln(k(0)) = 37.39 - 21900/RT，其中k(0)是普兰林肽降解的零级速率常数（%/月）。在pH = 4.0条件下配制的普兰林肽注射用产品极其稳定，在5℃下30个月内纯度百分比和效价百分比损失仅约2%。配制好的普兰林肽药品在5℃下长期储存具有可接受的保质期，在室温下储存时可供患者使用长达30天。
