A pyrroloquinoquinone（PQQ）-dopamine（DA）magnetic nanoparticle imprinted polymers were prepared by the combination of PQQ-DA and magnetic nano Fe3O4 as the core wrapped with SiO2,which possess high recognition and high selectivity toward PQQ-DA and have great advantages in the separation,purification and enrichment of low concentration compounds in complex matrix of brain tissue after molecular imprinting modification.The magnetic nanoparticles were applied in the determination of trace PQQ-DA in brain tissue samples by ultrahigh performance liquid chromatography-tandem mass spectrometry（UPLC-MS）.Results showed that,under the optimized conditions,there was a good linear relationship for PQQ-DA in the range of 0.02-0.1 mg/mL with a correlation coefficient（r2）of 0.996 6,and the detection limit was 0.2×10-11 mg/mL.The recoveries for brain tissue samples were in the range of 887%-955%,with relative standard deviations（n=6）of 2.6%-3.2%.The method could be used in the detection of trace PQQ-DA in vivo with high sensitivity and good repeatability.