2. Academic Validation
  3. Simultaneous analysis of avatrombopag, eltrombopag, and hetrombopag in human plasma by UPLC-MS/MS for therapeutic drug monitoring

Simultaneous analysis of avatrombopag, eltrombopag, and hetrombopag in human plasma by UPLC-MS/MS for therapeutic drug monitoring

  • J Pharm Biomed Anal. 2023 Oct 25:235:115683. doi: 10.1016/j.jpba.2023.115683.
Peile Wang 1,  Zhao Yin 2,  Fang Wang 3,  Jing Yang 4
Affiliations

Affiliations

  • 1 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.
  • 2 Department of Pharmacy, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, PR China.
  • 3 Departments of Haematology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, PR China. Electronic address: [email protected].
  • 4 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. Electronic address: [email protected].
PMID: 37647792 DOI: 10.1016/j.jpba.2023.115683
Abstract

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 C18 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.

Keywords

Plasma; Therapeutic drug monitoring; Thrombopoietin receptor agonist; UPLC-MS/MS.

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