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The dopamine, serotonin, and kynurenine metabolic pathways play pivotal roles on brain function and their disorders are closely related to various neurological diseases.Comprehensive measurement of these metabolites is thus essential for monitoring the global neurochemical responses to pathological challenges or drug interventions.However, simultaneous measurement of various neurochemcial metabolites represents a great challenge.We developed heroin an original and feasible method using high performance liquid chromatography-tandem mass spectrometry (LC-MS/MS).A chemical derivatization approach using benzoyl chloride (benzoylation) was developed to achieve better chromatographic behavior and mass detecting sensitivity.The developed method enables a rapid quantification of 11 metabolites spanning dopamine, serotonin, and kynurenine metabolic pathways within 10.5 min.This method was validated to be highly sensitive and robust to quantify all these metabolites from rat brain tissue and plasma matrix Fluctuations of this neurochemical panel in the cerebral cortex and plasma from a rat model of depression were successfully characterized and a different pattern of change was revealed between the brain and periphery.This study favors a rapid and feasible detection of a large panel of key neurochemcial metabolites, which is important for the understanding of the pathological mechanisms of various neurological disorders.