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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
Author(s) -
Wang Zhenlei,
Jia Shiling,
Zhang Quan,
Wang Yongsheng,
Huang Biao,
Zheng Li
Publication year - 2021
Publication title -
biomedical chromatography
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.4
H-Index - 65
eISSN - 1099-0801
pISSN - 0269-3879
DOI - 10.1002/bmc.5095
Subject(s) - chemistry , chromatography , pharmacokinetics , bioanalysis , acetic acid , high performance liquid chromatography , peptide , extraction (chemistry) , tandem mass spectrometry , mass spectrometry , liquid chromatography–mass spectrometry , acetonitrile , human plasma , ischemic stroke , solid phase extraction , analyte , pharmacology , biochemistry , medicine , ischemia
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