Department of Pharmacy, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, PR China; Henan Key Laboratory of Precision Clinical Pharmacy, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, PR China; Henan Engineering Research Center for Application & Translation of Precision Clinical Pharmacy, Zhengzhou University, Zhengzhou, PR China.
Department of Pharmacy, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, PR China.
J Pharm Biomed Anal. 2023 Oct 25;235:115683. doi: 10.1016/j.jpba.2023.115683. Epub 2023 Aug 25.
Avatrombopag, eltrombopag, and hetrombopag are three oral thrombopoietin receptor agonists used to treat thrombocytopenia. To investigate the pharmacokinetic properties, a fast and robust UPLC-MS/MS method was developed and validated for simultaneous determination of avatrombopag, eltrombopag, and hetrombopag in human plasma. Chromatographically separation was achieved on an Acquity BEH C column using a gradient elution of methanol-water (20:80, v/v) and acetonitrile containing 0.1% formic acid at a flow rate of 0.4 mL/min within 4.5 min. The linearity was assessed over the range of 7.5-1500 ng/mL for avatrombopag, 50-10,000 ng/mL for eltrombopag, and 5-1000 ng/mL for hetrombopag. This method was validated with adequate results in terms of selectivity, precision (intra- and inter-day CV from 4.2% to 12.2%), accuracy (RE from -6.6% to 7.5%), dilution integrity, carryover, recovery, matrix effects, as well as stability of the analytes under various conditions. The developed approach has been successfully applied to the therapeutic drug monitoring of avatrombopag, eltrombopag, and hetrombopag in patients with immune thrombocytopenia.
阿伐曲泊帕、艾曲泊帕和海曲泊帕是三种用于治疗血小板减少症的口服血小板生成素受体激动剂。为了研究其药代动力学特性，开发并验证了一种快速而强大的 UPLC-MS/MS 方法，用于同时测定人血浆中的阿伐曲泊帕、艾曲泊帕和海曲泊帕。在 Acquity BEH C 柱上，采用甲醇-水（20:80，v/v）和含 0.1%甲酸的乙腈的梯度洗脱，流速为 0.4 mL/min，在 4.5 分钟内实现色谱分离。阿伐曲泊帕的线性范围为 7.5-1500ng/mL，艾曲泊帕为 50-10000ng/mL，海曲泊帕为 5-1000ng/mL。该方法在选择性、精密度（日内和日间 CV 为 4.2%-12.2%）、准确度（RE 为-6.6%-7.5%）、稀释完整性、交叉污染、回收率、基质效应以及各种条件下分析物的稳定性方面均获得了充分的验证结果。该方法已成功应用于免疫性血小板减少症患者中阿伐曲泊帕、艾曲泊帕和海曲泊帕的治疗药物监测。
