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Biomedical chromatography : BMC. 2025 Jan;39(1):e6039. doi: 10.1002/bmc.6039 Q41.82024

A novel, sensitive, and fast ultra-high-performance liquid chromatography tandem mass spectrometry method for TNG908 determination in dog plasma and pharmacokinetic study

一种新颖、灵敏、快速测定狗血浆中TNG908的UPLCTQ-MS/MS方法及其药动学研究 翻译改进

Weiwei Zhu  1, Huiying Zhang  1, Fan Li  1

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  • 1 Department of Pharmacy, Xuzhou Central Hospital, Xuzhou, China.
  • DOI: 10.1002/bmc.6039 PMID: 39510096

    摘要 Ai翻译

    TNG908 is a potent and selective protein arginase methyltransferase 5 (PRMT5) inhibitor that is currently going through phase I/II clinical development for the treatment of non-small cell lung cancer. To facilitate pharmacokinetic and toxicokinetic studies of TNG908, here, we reported an ultra-high-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method for the detection of TNG908 in dogs. The dog plasma samples were precipitated by acetonitrile and analyzed using a Waters ACQUITY BEH C18 column combined with a Thermo triple quadrupole mass spectrometer. The mobile phase consisted of 0.1% formic acid solution and acetonitrile, at a flow rate of 0.3 mL/min. TNG908 and internal standard were monitored by selective reaction monitoring (SRM) with m/z 410.2 > 150.1 and m/z 394.2 > 278.1, respectively. The method demonstrated excellent linearity over the concentration range of 1-1000 ng/mL, with a correlation coefficient greater than 0.995. Acetonitrile-mediated protein precipitation showed high extraction efficiency and a recovery above 80%. The validated assay was further applied to measure TNG908 in dog plasma after oral and intravenous administration and achieved success. The obtained pharmacokinetic parameters indicated low clearance of TNG908 (3.7 ± 0.8 mL/min/kg) and moderate oral bioavailability (>36.4%).

    Keywords: PRMT5 inhibitor; TNG908; UPLC‐MS/MS; pharmacokinetics.

    Keywords:mass spectrometry method

    Copyright © Biomedical chromatography : BMC. 中文内容为AI机器翻译,仅供参考!

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    期刊名:Biomedical chromatography

    缩写:BIOMED CHROMATOGR

    ISSN:0269-3879

    e-ISSN:1099-0801

    IF/分区:1.8/Q4

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    A novel, sensitive, and fast ultra-high-performance liquid chromatography tandem mass spectrometry method for TNG908 determination in dog plasma and pharmacokinetic study