Stability of Ketamine-Xylazine-Butorphanol formulation supports evidence-based beyond-use date

Researchers at Auburn University have demonstrated that a widely used sedation formulation for New World Camelids—combining 8.3% w/v ketamine, 0.83% w/v xylazine, and 0.083% w/v butorphanol—maintains chemical and microbial stability for at least three months. The study, published in Current Topics in Anesthesiology, provides critical evidence supporting a 28-day beyond-use date (BUD) under USP <797> Category 2 guidelines for compounded sterile preparations.

Using a validated stability-indicating HPLC method, the team found that all three drugs remained within 90–110% of their initial concentrations after three months of storage at both room temperature (23°C) and 40°C. No significant changes in appearance or pH were observed throughout the study period. Microbiological testing showed no bacterial or fungal growth at 28 or 45 days, even under simulated clinical-use conditions.

"Our method separates all three active ingredients from one another and from degradation products, confirming that the formulation remains effective and safe throughout its intended use," said corresponding author Susan M. Elrod. Forced degradation studies confirmed the HPLC assay's specificity, with oxidative stress causing the only notable degradation, particularly affecting butorphanol.

The authors conclude that the evidence robustly supports the 28-day BUD, offering veterinary hospitals a science-backed foundation for preparing and using this multi-drug combination in llamas, alpacas, and other large animals.