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

PURPOSE: 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.

METHODS

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.

FINDINGS: 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.

IMPLICATIONS: 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.