Evaluating the stability of colistin and colistin methanesulphonate in human plasma under different conditions of storage.
OBJECTIVE
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 ( approximately 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.
Dudhani
Rajesh V
RV
Facility for Anti-infective Drug Development and Innovation, Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, Melbourne, Australia.
Nation
Roger L
RL
Li
Jian
J
D000900:Anti-Bacterial Agents / Q000032:analysis* / Q000493:pharmacokinetics; D002851:Chromatography, High Pressure Liquid; D003091:Colistin / Q000031:analogs & derivatives* / Q000032:analysis* / Q000493:pharmacokinetics; D004355:Drug Stability; D005615:Freezing; D006801:Humans; D010949:Plasma / Q000737:chemistry*; D013048:Specimen Handling / Q000379:methods*; D013997:Time Factors
D000900:Anti-Bacterial Agents; D003091:Colistin