Physicochemical stability of sufentanil and esketamine containing analgesic mixtures applied for patient-controlled intravenous analgesia.

BACKGROUND

Sufentanil combined with esketamine for patient-controlled intravenous analgesia (PCIA) is an efficient options for postoperative pain control, which can result in a shortened hospital stay. However, no commercially formulated admixture of these two agents is currently available for clinical use. Furthermore, to date, no published data exist regarding the physicochemical stability of sufentanil and esketamine co-dissolved in 0.9% sodium chloride injection. The study aims to assess the stability of sufentanil and esketamine in infusion at both room temperature (25 °C) and refrigerated conditions (4 °C).

METHODS

Commercial available injectable formulations of sufentanil and esketamine were were aseptically combined and diluted with 0.9% sodium chloride injection to yield final concentrations of 1.0 µg/mL sufentanil and 0.25, 0.5, or 1.0 mg/mL esketamine. The resulting admixtures were stored in polyvinyl chloride (PVC) infusion bags and assessed for compatibility and stability over 14 days at 4 °C and over 48 h at 25 °C. Stability was evaluated through visual inspection (for precipitation or discoloration), pH measurement, and quantitative analysis of drug concentrations using validated liquid chromatography-tandem mass spectrometry (LC-MS/MS).

RESULTS

All admixtures remained physically stable-no precipitation, turbidity, or color change was observed throughout the study period. The pH values varied by less than 0.80 units across all batches and time points under both storage conditions. Both sufentanil and esketamine retained ≥ 95% of their initial concentrations at all tested time points and temperatures.

CONCLUSION

Sufentanil (1.0 µg/mL) combined with esketamine (0.25, 0.5, or 1.0 mg/mL) in 0.9% sodium chloride injection demonstrated chemical and physical stability for up to 14 days under refrigerated storage and for up to 48 h under room-temperature conditions when contained in PVC infusion bags.