Evaluating the stability of colistin and colistin methanesulphonate in human plasma under different conditions of storage

Objectives: The purpose of this study was to assess the stability of colistin and colistin methanesulphonate (CMS) in human plasma under storage conditions typically used in clinical pharmacokinetic (PK) and PK/pharmacodynamic (PD) investigations. Methods: Human plasma (pH adjusted to 7.4) containing colistin (2 mg/L) or CMS (2 or 30 mg/L) was stored at -20, -70 or -80 degrees C for 6-12 months. At periodic intervals, the concentrations of colistin in colistin-spiked samples, and of CMS and formed colistin in CMS-spiked samples, were analysed (n=3 replicates at each time) by HPLC. Results: The time course of colistin concentrations in colistin-spiked plasma showed a substantially better stability at -80 and -70 degrees C than at -20 degrees C. With regard to CMS-spiked plasma of 2 and 30 mg/L stored at -80 and -70 degrees C, no quantifiable colistin formed over a 4 month period. However, the plasma spiked to 2 mg/L stored at -20 degrees C showed a substantial concentration of colistin (similar to 0.4 mg/L) within 2 months. At all three storage temperatures, the stability of CMS was substantially better for the plasma spiked to contain 30 mg/L as compared with 2 mg/L. Conclusions: The results of our long-term stability study have significant implications for those involved in conducting clinical PK and PK/PD studies with CMS/colistin.