Physicochemical Stability and Pharmaceutical Compatibility of Ciprofol with Five Adjuvant Drugs for Gastrointestinal Endoscopy: An In Vitro Evaluation

Background/Objectives: Ciprofol is a novel GABAₐ-receptor agonist sedative widely used for gastrointestinal endoscopic sedation–anesthesia due to its rapid onset, fast recovery and favorable cardiovascular tolerance. Intravenous anesthetic drug administration via Y-site co-infusion is a common clinical practice during endoscopic procedures, yet systematic physicochemical compatibility data for ciprofol with adjuvant injectable agents remain limited. Methods: In this in vitro study performed under static laboratory conditions, ciprofol injection was mixed 1:1 (v/v) with lidocaine, nicardipine, norepinephrine, cisatracurium besilate and atropine at clinical concentrations and stored at (25 ± 1) °C. Multiple physicochemical indicators, including macroscopic–microscopic morphology, pH, zeta potential, droplet size and polydispersity index (PDI), osmolality, and residual drug content, were evaluated at 0, 2, 4, 6 and 8 h. Results: No macroscopic abnormalities were observed for all admixtures. The cisatracurium besilate group showed a 0.6-unit pH shift, whereas pH changes in the other groups were within ±0.2. Droplet size remained at 200–210 nm, with a PDI < 0.2, and osmolality varied below 5%. The lidocaine admixture exhibited a low zeta potential (~5 mV) and obvious droplet aggregation under microscopy. Chemically, cisatracurium besilate degraded below 50% of baseline, while atropine, norepinephrine and nicardipine maintained 95–105% of their initial concentrations. Conclusions: Under static in vitro mixing conditions at (25 ± 1) °C, admixtures of ciprofol with atropine, nicardipine and norepinephrine displayed no obvious signs of physicochemical destabilization over 8 h. Co-administration with cisatracurium besilate and lidocaine should be avoided owing to severe chemical degradation or droplet aggregation. These experimental findings provide laboratory-derived reference evidence for safe pharmaceutical compounding and rational intravenous co-administration during gastrointestinal endoscopic procedures.