Abstract: ObjectiveTo compare the differences between the glasy carbon electrode electrochemical method and liquid chromatogra-phy-tandem mass spectrometry(LC-MS/MS) in the determination of fat-soluble vitamins A/D,/E/K,,and to explore the optimization strategies.MethodsThe concentrations of fat-solublevitamins in 90serum samples weredetermined bydifferentialpulse voltammetry withglascabonelctrdandliquidcromatgraphtandemmassspctme-msrespctivelyThedetetiolimi precisions,accuracies and correlations of the two methods were compared. The electrochemical detection conditions of glassy carbon electrodewereoptimizedbyresponsesurfacemethodology.ResultsThedetectionlimitsoftheglassycarbonelectrodeelectrochemical method were 0.08 p.g/mL for vitamin A, O.15 ng/mL for vitamin D,,O.12 pg/mL for vitamin E, and O.25 ng/mL for vitamin K,， and those of the IC-MS/MS method were 0.02 pg/mL,O.05 ng/mL, O.03 pg/mL, and 0.08 ng/mL, respectively. The correlation between the two methods was strong (r>O.85),but the electrochemical method showed better stability in the determination of vitamin E. After optimization,the detection time of the electrochemical method was shortened to 8 minutes,and the cost was reduced by 60%. ConclusionThe glassy carbon electrode electrochemical method has the advantages of rapidity and economy，and is suitable for routine clini- cal screening.The LC-MS/MS method issuperior in sensitivity and specificity,and is suitable for precise quantitative analysis.The two methods can be complementary and applied to meet different clinical requirements.