安瑞克芬注射液与多模式镇痛4类常用药物配伍的理化稳定性研究

Study on the Physicochemical Stability of Anrikefon Injection in Compatibility with Four Types of Common Drugs for Multimodal Analgesia

摘要

目的 考察安瑞克芬（研发代号：HSK21542）注射液与多模式镇痛中常用药物（阿片类、α₂肾上腺素受体激动剂、非甾体抗炎药及5-羟色胺3受体拮抗剂）的理化配伍稳定性，为临床合理联合用药及安全提供实验依据。方法 将安瑞克芬（0.2 mg）分别与枸橼酸舒芬太尼、盐酸右美托咪定、氟比洛芬酯、盐酸托烷司琼等11种药物按临床常用剂量配伍，用0.9%氯化钠注射液稀释至200 mL，在22 ~ 25 ℃、避光、相对湿度37%条件下，于0、8、24、48、72 h检测配伍溶液的外观性状、pH值、不溶性微粒及安瑞克芬含量。实验设8组配伍方案，含对照组（安瑞克芬单用，以0.9%氯化钠注射液稀释至同体积）及不同药物组合，每组平行制备2份样品。结果 所有配伍方案在观测期内外观稳定（含氟比洛芬酯时为白色乳状，其余为无色澄明，且无浑浊、无沉淀、无肉眼可见异物）；pH值均为4.0 ~ 9.0；不溶性微粒数量（直径≥10 μm的微粒：＜100粒/200 mL；直径≥25 μm的微粒：＜10粒/200 mL）远低于2020年版《中华人民共和国药典》（四部）限值。安瑞克芬在各配伍方案中的药物含量均维持在初始值的90% ~ 110%，符合标准。结论 除不适用于某些检测的情况外，安瑞克芬与术后镇痛泵中常见的配伍药物（包括枸橼酸舒芬太尼、盐酸右美托咪定、酮咯酸氨丁三醇、盐酸托烷司琼等）混合后，可在22 ~ 25 ℃避光条件下72 h内保持理化性质稳定，可用于多模式镇痛方案。

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 ofChinese 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.

关键词

安瑞克芬注射液 / 多模式镇痛 / 阿片类药物 / 配伍 / 稳定性

Key words

anrikefon injection / multimodal analgesia / opioid drugs / compatibility / stability

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