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Yangxin Dingji Capsules (YXDJ), derived from Zhigancao Decoction, are used clinically for arrhythmia. Four D101 macroporous-resin purification procedures involving different Asini Corii Colla incorporation modes and elution solvents were compared; the co-decoction procedures additionally included centrifugation and filtration before resin purification. The unpurified preparation and four purified preparations were characterized by UPLC-Q-TOF-MS/MS and evaluated in a barium chloride-induced rat arrhythmia model using electrocardiographic, biochemical, and histopathological indicators. Fifty-five constituents were tentatively identified. The 60% ethanol-eluted preparations CF1 and CF3 retained 52 and 51 constituents, respectively, whereas the water-eluted preparations CF2 and CF4 retained 21 and 14. CF1 showed the highest Pearson correlation with YXDJ among the purified preparations (r = 0.520), while CF3 had the highest five-indicator comprehensive pharmacodynamic score among the purified preparations (CPS5 = 3.540); unpurified YXDJ scored 3.827. Compared with the model group, CF3 significantly increased heart rate, shortened QRS duration, reduced serum lactate dehydrogenase, and increased Na⁺/K⁺-ATPase activity. Exploratory one-component partial least-squares variable-importance and gray relational analyses generated a provisional list of 12 constituents for subsequent targeted quantification and pharmacological verification.