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Simultaneous Determination of TUG-891 and Its Metabolites in Rat Plasma Using LC-HRMS With Application to Preclinical Pharmacokinetic Study

Simultaneous Determination of TUG-891 and Its Metabolites in Rat Plasma Using LC-HRMS With Application to Preclinical Pharmacokinetic Study

Jiping Yi, Bin Chen, Yongzheng Bao, Jingyu Wang

Biomed Chromatogr. 2020 Apr 28;e4870.

PMID: 32346871

Abstract:

In this study, a simple and reliable LC-MS/MS method was first proposed for the simultaneous determination of TUG-891 and its metabolites TUG-891-alcohol, TUG-891-aldehyde, and TUG-891-acid in rat plasma. The analytes and fasiglifam (internal standard) were extracted from plasma samples with acetonitrile and separated using an Acquity BEH C18 column (1.7 μm, 2.1 × 50 mm) with water containing 0.05% ammonium hydroxide and acetonitrile containing 0.05% ammonium hydroxide as the mobile phase. A Q-Exactive Orbitrap mass spectrometer in full-scan mode was used for mass detection, and the data analysis was obtained using a mass extraction window of 5 ppm. The calibration curves exhibited excellent linearity (correlation coefficient > 0.9981) in the concentration range of 0.5-1000 ng/mL. The lower limit of quantification was 0.5 ng/mL for all analytes. The intra- and inter-day precision was less than 11.31%, and the accuracy ranged from -11.50 to 9.50%. The extraction recovery of the analytes from rat plasma was greater than 82.31%, and no obvious matrix effect was found. The established method was further applied to the pharmacokinetic study of TUG-891, TUG-891-alcohol, TUG-891-aldehyde, and TUG-891-acid in rat after a single dose of 5-mg/kg treatment of TUG-891. The results demonstrated that TUG-891 was rapidly metabolized into its metabolites and the systemic exposures of the metabolites were much higher than those of TUG-891.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP1374516070	TUG-891		1374516-07-0	Price

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