Ciprofol Injection Combined With 6 Cephalosporins During Simulated Y-site Mixing: A Physicochemical Compatibility...

Simultaneous administration of multiple drugs via Y-site infusion is a common practice during the perioperative period; however, in-line incompatibility remains a significant safety concern. Ciprofol injection, a novel intravenous anesthetic based on lipid emulsifiers, may exhibit compromised stability when co-administered with other medications. This study systematically evaluated the compatibility and stability of ciprofol injection with 6 commonly used cephalosporins (cefazolin, cefuroxime, cefradine, cefotaxime, ceftriaxone, and cefoperazone) during Y-site infusion to ensure the safe and rational use of perioperative intravenous therapies.

Ciprofol injection was mixed with clinically relevant concentrations of 6 cephalosporins in 0.9% sodium chloride or 5% glucose solution at a 1:1 volume ratio under ambient conditions (25 ± 1°C). Samples were collected at predetermined time points (0, 2, 4, 6, and 8 hours) for comprehensive evaluation of physical and chemical properties, including appearance, pH value, Zeta potential, particle size/polydispersity index (PDI), osmotic pressure, and relative percentage content changes of the mixtures.

Within an 8-hour period, no visible changes in the appearance of any drug mixture were observed. The pH values fluctuated within ±0.5, while the average particle size remained stable at (215 ± 10) nm with uniform particle size distribution (PDI = 0.12 ± 0.04). The Zeta potential and osmotic pressure values exhibited stability throughout the study period. The relative drug content was maintained between 95% and 105%. Microscopic imaging analysis showed that there was no aggregation of milk droplets or abnormal increase of particle size in the mixture.

Under conditions of room temperature, ciprofol injection demonstrated compatibility and stability when administered via Y-site infusion with 6 commonly used cephalosporins at clinical dosage concentrations for up to 8 hours. These findings provide valuable guidance for the safe and effective use of ciprofol in perioperative settings.