The purpose of thispaperis to study the migration of 13 chemicals from PVC/LDPE composite hard tablet into calcium zinc gluconate oral solution and its simulants by ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS), andto assess their safety. Prepare lactic acid solution with volume fraction of 0.6%, 1.25% and 2.5% as food simulation solution, and conduct migration test according to the requirements of GB 31604.1—2015.The original oral solution and its simulants after immersion are filtered and injected. Quantitative analysis is carried out in H-ESI+ and H-ESI− modes respectively. The results areassessed by means of threshold of toxicological concern (TTC).The 13 chemicalsin oral solution and its food simulant have good linearity in their corresponding concentration range, R2 is greater than 0.99, the spike-and-recoveryrange of each substance at three concentration levels are 82.7%-120%, and the relative standard deviation is 1.1%-11%.The migration amount of each substance is lower than the specified limit in GB 9685-2016 and TTC and the calculated theoretical allowable migration amount. The detection method studied in this paper can sensitively and accurately determine the migration of 13 target chemicalsin calcium zinc gluconate oral solution and its simulants. The sources of 13 chemicalscan be divided into intentionally added plastic additives, non-intentionally added substances and solvent residues. Their safety assessment is conducted separately. The results show that the maximum migration amount is lower than the limit requirements, and the exposure amount is lower than the maximum daily intake calculated by TTC method. Therefore, it is preliminarily considered that the safety risk is low.