Abstract: Objective This study aimed to investigate the physicochemical compatibility of anrikefon (HSK21542) injection with commonly used drugs for multimodal analgesia, including opioids, α2-adrenergic receptor agonists, nonsteroidal anti-inflammatory drugs, and 5-hydroxytryptamine 3 receptor antagonists, so as to provide experimental basis for rational clinical combined medication and safe clinical application. Methods Anrikefon (0.2 mg) was combined with 11 drugs (such as sufentanil citrate, dexmedetomidine hydrochloride, flurbiprofen axetil, tropisetron hydrochloride, etc.) at clinically common doses. The mixtures were diluted to 200 ml with 0.9% sodium chloride injection. The appearance, pH value, insoluble particles, and the anrikefon content of the compatible solutions were detected at 0, 8, 24, 48, and 72 hours under conditions of 22 ~ 25 ℃, darkness, and 37% humidity. Eight compatibility schemes were designed, including a control group (anrikefon used alone and diluted to the same volume with 0.9% sodium chloride injection) and various drug combination groups, with two parallel samples prepared for each group. Results All compatibility schemes showed stable appearance during the observation period, with flurbiprofen axetil-included samples appearing as white emulsions and the others as colorless and clear，without turbidity, precipitation, or visible foreign matter. All samples demonstrated pH values within the 4.0 ~ 9.0 range, and insoluble particle counts (particles with diameter ≥ 10 μm: ＜ 100 particles/200 mL;particles with diameter ≥ 25 μm: ＜ 10 particles/200 mL) were far below the thresholds defined in 2020 Edition of Chinese Pharmacopoeia (Volume Ⅳ). Anrikefon content in all compatibility schemes remained within 90% ~ 110% of the initial concentration, meeting the stability standards. Conclusion Except for cases involving non-applicable tests, anrikefon demonstrated physicochemical stability for up to 72 hours when combined with common combination drugs in postoperative analgesic pumps (including sufentanil citrate, dexmedetomidine hydrochloride, ketorolac tromethamine, tropisetron hydrochloride, etc.) under conditions of room temperature 22 ~ 25 ℃ and darkness, suggesting its applicability in multimodal analgesia regimens.