Influence of pH and temperature on ziconotide stability in intrathecal analgesic admixtures in implantable pumps and syringes.
PURPOSE
The aim of our study was to investigate the influence of pH and temperature on the stability of ziconotide in analgesic admixtures containing morphine and ropivacaine.


METHODS
All admixtures were combined using a wide range of concentrations, in implantable pumps and syringes, using temperatures from 4°C to 37°C. Quantification was made thanks to a specific chromatographic technique. pH has also been measured throughout the study.


RESULTS
Admixtures confirm excellent stability for morphine and ropivacaine. Concerning ziconotide, an acid hydrolysis has been observed, reducing the time of use of our admixtures in a significant way, but producing non-toxic degradation products. The degradation was linear in all conditions. Inside the implantable pumps at body temperature turned out to be the best conditions for lower protein breakdown. Finally the degradation process showed a high correlation with the pH and the morphine concentration with a median loss of concentration delay due to degradation of 3.5 days [3; 5] when pH<4.5 and 13 days [13; 24] when pH ≥ 4.5.


CONCLUSION
Our admixtures showed different stability depending on the drug concentrations, pH and temperature. The great majority of mixtures in real life in our institution have stability highly compatible with our practice and with the delay between two pump refilling.
['Bazin|Christophe|C|', 'Poirier|Anne-Lise|AL|', 'Dupoiron|Denis|D|']
D000700:Analgesics D002851:Chromatography, High Pressure Liquid D004338:Drug Combinations D004355:Drug Stability D006863:Hydrogen-Ion Concentration D015918:Infusion Pumps, Implantable D007278:Injections, Spinal D015203:Reproducibility of Results D013594:Syringes D013696:Temperature D020960:omega-Conotoxins
Ziconotide Stability Intrathecal Morphine Ropivacaine Analgesia Methionine (PubChem CID: 6137) Morphine sulphate (PubChem CID: 5464280) Ropivacaine (PubChem CID: 175805) Ziconotide (PubChem CID: 16129690)