Long-term stability of an infusion containing paracetamol, alizapride, ketorolac and tramadol in glass bottle at 5±3°C

Background and objective

Infusion containing paracetamol, alizapride, ketorolac and tramadol is used after a general anaesthesia in order to limit pain, fever and nausea. Currently, these infusions are prepared according to demand in the anaesthesia unit, but the preparation in advance could improve quality of preparation and time management. The aim of this study was to investigate the long-term stability of this infusion in glass bottle at 5±3°C.

Method

Five bottles of infusion were stored at 5±3°C for 60 days. A visual and microscope inspection were performed periodically to observe any particle appearance or colour change. pH and absorbance at 3 wavelengths were measured. The concentrations were measured by Ultra-High Performance Liquid Chromatography (UHPLC) – diode array detection.

Results

Multiple verifications were performed during the first 35 days and no crystal, impurity or colour change were observed. At the next time point (42th day), crystals were visible to the naked eye. pH and absorbance at 350 nm and 550 nm were stable. A slight increase of the absorbance at 410 nm was observed during the study, suggesting that a degradation product could be formed and absorb at this wavelength.

The infusion was considered chemically stable while the lower one-sided prediction limit at 95% remains superior to 90% of the initial concentration. Concentration measurements demonstrated that ketorolac and alizapride remained stable in the infusion for 35 days. Stability of tramadol was 28 days. However, degradation of paracetamol was much faster given that concentration has fallen below 90% of the initial concentration after 7 days.

Conclusion

Infusion of paracetamol, alizapride, ketorolac and tramadol remains stable for 7 days in glass bottle at 5±3°C and could be prepared in advance with these storage conditions.