OBJECTIVE：To establish the metho d for the concentration det ermination of foretinib derivative LWK- 126 in liver microsomes，and to study its metabolism stability in liver microsomes of rats ，Beagle dogs and human. METHODS ：In the in vitro incubation system of liver microsomes ，LWK-126 was dissolved in liver microsomal incubation systems of rats ，Beagle dog and human initiated by reduced nicotinamide adenine dinucleotide phosphate solution. After incubation in water at 37 ℃ for 0，5，10，20， 30 and 60 min，the reaction was terminated with acetonitrile containing internal standard （1 μg/mL tolbutamide）. UPLC-MS/MS method was applied to determine the concentration of LWK- 126 in the incubation systems. The determination was performed on Waters BEH C 18 column with mobile phase consisted of water （containing 0.1％ formic acid ）-acetonitrile（containing 0.1％ formic acid）by gradient elution at the flow rate of 0.4 mL/min. The column temperature was 30 ℃，and the sample size was 2 μL. The mass spectral analysis was performed in a positive electrospray ionization mode ，and the full MS experiment was run with the selective reaction monitoring mode with a scanning range of m/z 50→1 200. Taking the concentration of LWK- 126 at 0 min as reference，the remaining percentage and the enzyme kinetic parameters were calculated. RESULTS ：The linear range of LWK- 126 was 0.05-15 μg/mL（R 2＝0.999 2）；the lower limit of quantification was 0.05 μg/mL，and the lowest detection limit was 0.01 μg/mL. The precision，accuracy，extraction recovery and matrix effect all met the analysis requirements of biological samples. The remaining percentage of LWK- 126 in liver microsomes of human ，rats and Beagle dogs for 60 min were （33.17±4.52）％，（3.14± 6.73）％，（1.38±5.85）％；t1/2 of them were 33.15，11.76，5.62 min；the clearance rates were 38.45，118.81，245.76 μL（/ min·mg）， respectively. CONCLUSIONS ：The method for the content ； determination of LWK- 126 in liver microsomes is established successfully. The order of metabolic stability of LWK- 126 in 〔2016〕4015） liver microsomes of different species is human ＞rats＞Beagle dogs.