Abstract: Icodextrin peritoneal dialysis solution may produce cytotoxic α-dicarbonyl degradation products during heat sterilization, which must be monitored and controlled. The study established an o-phenylenediamine (OPD) derivatization HPLC-MS/MS method for the detection of these degradation products, enabling qualitative and quantitative analysis of α-dicarbonyl degradation products in icodextrin peritoneal dialysis solution. The results indicated that the main α-dicarbonyl degradation products in icodextrin peritoneal dialysis solution are 3-deoxyglucosone (3-DG), 3-deoxygalactosone (3-DGal), 4-deoxyglucosone (4-DG), and 3,4-dideoxyglucosone-3-ene (3,4-DGE), along with two monocarbonyl degradation products, furfural and 5-hydroxymethylfurfural. The quantitative method for 3-DG, 3-DGal, 3,4-DGE and their structural analog, glucosone, was validated. 3-DG, 3-DGal, and glucosone exhibited good linear relationships within the range of 5-150 ng/mL, while 3,4-DGE showed good linearity in the range of 1-150 ng/mL. The spiked recovery rates for all compounds were between 86.8% and 100.0%. The detection limits for glucosone, 3-DG, and 3-DGal were approximately 2.4 ng/mL, and approximately 0.5 ng/mL for 3,4-DGE. The method established in this study can accurately determine α-dicarbonyl degradation products in icodextrin peritoneal dialysis solution, providing an important basis for the quality control.