LC–MS/MS assay for the determination of tat‐K13, a novel interfering peptide for the treatment of ischemic stroke, in human plasma and its application to a pharmacokinetics study. (2nd March 2021)

• Record Type: Journal Article
• Authors: Wang, Zhenlei; Jia, Shiling; Zhang, Quan; Wang, Yongsheng; Huang, Biao; Zheng, Li
• Is Part Of: Biomedical chromatography. Volume 35:Number 7(2021)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2021-03-02
• Subjects: first‐in‐human -- pharmacokinetics -- stroke -- tat‐K13 -- UPLC–MS/MS; Chromatographic analysis -- Periodicals; Biology -- Periodicals; Medicine -- Periodicals; Biology -- Periodicals; Chromatography -- methods -- Periodicals; Medicine -- Periodicals; 543.089
• DOI: 10.1002/bmc.5095
• Languages: English
• ISSNs: 0269-3879

Abstract

Abstract: A sensitive and robust method has been developed using an ultra‐performance liquid chromatography tandem mass spectrometry (UPLC–MS/MS) assay to quantify Tat‐K13, a novel interfering peptide for the treatment of ischemic stroke, in human plasma. Automated solid‐phase extraction on a Waters Oasis WCX (30 μm, 10 mg) 96‐well plate was used to extract Tat‐K13 from human plasma and the extracts were separated on a Waters Acquity CSH column (2.1 × 50 mm i.d., 1.7 μm) with a gradient elution method by mobile phase A (nonafluoropentanoic acid–acetic acid–water, 1:2:1000, v/v/v) and B (nonafluoropentanoic acid–acetic acid–water–acetonitrile, 1:2:100:900, v/v/v/v). The method was fully validated following international bioanalytical guidelines and showed good linearity from 2.10 to 1, 050 ng/ml. The method was successfully applied to investigate the clinical pharmacokinetics of Tat‐K13 in health volunteers. Rapid elimination of Tat‐K13 from the body was observed, with half‐life ranging from 0.26 to 0.78 h across different dose levels. The exposure of Tat‐K13 was approximately dose‐dependent in terms of the area under the concentration–time curve and peak concentration