Preclinical PK investigation of a novel IDO1/TDO dual inhibitor-SHR9146 in mouse plasma and tissues by LC-MS/MS.

ABSTRACT:

Purpose

The aim of the present study was to establish a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the determination of SHR9146, a novel IDO1/TDO dual inhibitor, in mouse plasma and tissues, and to apply it to investigate the preclinical plasma pharmacokinetics and tissue distribution of SHR9146 in mice.

Methods

Samples were spiked with deuterated SHR9146-d₄ as an internal standard and pretreated by protein-precipitation extraction with methanol. Chromatographic separation was performed on a Venusil ABS C18 column (150 × 4.6 mm, 5 μm) by isocratic elution with 10 mM ammonium acetate buffer containing 0.1% formic acid solution and methanol as mobile phases. MS detection was conducted in positive electrospray ionization with multiple reacti

SUBMITTER: Xiao M 

PROVIDER: S-EPMC10410440 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature