The invention belongs to the technical field of drug detection, and particularly relates to a method and a kit for detecting 19 drugs and metabolites thereof in blood through liquid chromatography-tandem mass spectrometry. The substances to be detected comprise sulpiride, pentafluridol, mianserin, buspirone, tandospirone, hydroxyazine, diazepam, venlafaxine, moclobemide, imipramine, paroxetine, reboxetine, amitriptyline, sertraline, digoxin, clonazepam, clopidogrel, toluenesulfobutyl urea, glimepiride, 1-pyrimidinepiperazine, desmethylvenlafaxine, 6-hydroxy buspirone and normipramine, and the substances to be detected are selected from the group consisting of sulpiride, pentafluridol, mianserin, venlafaxine, metandospirone, metandospirone, hydroxazine, diazepam, venlafaxine, moclobemide, the pharmaceutical composition is prepared from noramitriptyline, nordiazepam and clopidogrel metabolite; the detection method comprises the following steps: calibrating a standard solution, treating a to-be-detected sample, and detecting the to-be-detected sample by adopting high performance liquid chromatography-mass spectrometry. The embodiment of the invention can quickly and accurately measure the content, and the sample treatment method is simple and easy to implement, high in sensitivity and accurate in quantification.