Cebranopadol is a novel, centrally acting, potent, first-in-class analgesic drug candidate with a unique mode of action that combines nociceptin/orphanin FQ peptide receptor and opioid peptide receptor agonism. The present study aimed to develop and validate a novel UHPLC-MS/MS method to quantify cebranopadol in rabbit plasma and to assess its pharmacokinetics in rabbits after subcutaneous (s.c.) administration. Twelve adult females were administered with 200 µg/kg s.c. injection. Blood samples were withdrawn at 15, 30 and 45 min and 1, 1.5, 2, 4, 6, 8, 10 and 24 hr after administration. The plasma samples were extracted with a liquid/liquid extraction. The new analytical method complied with the EMA requirements for the bioanalytical method validation. The method was selective, repeatable, accurate, precise and robust with a lower limit of quantification of 0.1 ng/ml. In all the rabbits, cebranopadol was quantifiable from 0.25 to 10 hr. Mean Cmax and Tmax were 871 ng/ml and 0.25 hr, respectively. Further studies including the i.v. administration are necessary to fully evaluate the pharmacokinetic features of this novel active compound.

中文翻译：

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Cebranopadol，一种新型的一流候选药物：方法验证和首次在兔中进行的探索性药代动力学研究

Cebranopadol 是一种新型、中枢作用、强效、一流的镇痛候选药物，具有独特的作用模式，结合了伤害感受肽/孤啡肽 FQ 肽受体和阿片肽受体激动作用。本研究旨在开发和验证一种新的 UHPLC-MS/MS 方法来量化兔血浆中的 cebranopadol 并评估其在兔皮下 (sc) 给药后的药代动力学。12 名成年女性以 200 µg/kg 皮下注射给药。在给药后 15、30 和 45 分钟以及 1、1.5、2、4、6、8、10 和 24 小时抽取血样。血浆样品采用液/液萃取法进行萃取。新的分析方法符合 EMA 对生物分析方法验证的要求。该方法具有选择性、可重复性、准确度、精确而稳健，定量下限为 0.1 ng/ml。在所有兔子中，cebranopadol 可在 0.25 至 10 小时内定量。平均 Cmax 和 Tmax 分别为 871 ng/ml 和 0.25 小时。包括静脉给药在内的进一步研究对于全面评估这种新型活性化合物的药代动力学特征是必要的。