Abstract: Additives containing metal ions can be added to food contact plastic as stabilizer, catalyzer, colorant, etc. Food safety standards also request specific migration limits (SMLs) for metal elements. The most common methods for determination of multiple metal elements in solutions are inductively coupled plasma-optical emission spectrometry (ICP-OES) and inductively coupled plasma-mass spectrometry (ICP-MS). Metal ions in solution can cluster or coordinate with organic compounds to form new stable complicated ions, which can be detected by electrospray ionization-mass spectrometry (ESI-MS). To apply this nature for determination of metal ions by liquid chromatography-quadrupole time-of-flight mass spectrometry (LC-QTOF MS), further parameter optimization is needed. In this study, five kinds of aqueous mobile phases, including 0.02% (W/W) glycollic acid, 0.02% (V/V) formic acid, 0.10% (V/V) formic acid, 5 mmol/L ammonium formate, and 5 mmol/L ammonium formate-0.02% (V/V) formic acid, were compared for better performance of MS analysis coupled to Ultimate Hilic amide column. Different acids can give rise to form different cluster ions. Higher concentration of formic acid in aqueous mobile phase can produce better peak shape but doesn’t enhance signal to noise ratio apparently. Addition of ammonium ions can weak the signal of cluster ions. With 0.02% formic acid as the mobile phase, Cd²⁺, Co²⁺, Mn²⁺, Ni²⁺, Zn²⁺ form M(HCOO)+CH₃CN⁺ parent ion, while Cu²⁺ forms M+2CH₃CN⁺ parent ion. The parent ions of Cd²⁺, Co²⁺, Mn²⁺ and Zn²⁺ are collided to form M⁺, M(H)⁺, M(H)+CH₃CN⁺, M(HCOO)⁺, while the parent ion of Ni²⁺ to form Ni⁺, Ni(H)⁺, Ni+CH₃CN⁺, Ni(H)+CH₃CN⁺, Ni+CH₃CN+N₂⁺, NiO+CH₃CN⁺, Ni(OH)+CH₃CN⁺, the parent ion of Cu²⁺ to form Cu⁺, Cu+CH₃CN⁺, Ni+CH₃CN+N₂⁺. Finally, the optimized LC-QTOF MS method was applied to determine the migration of Cd²⁺, Co²⁺, Cu²⁺, Mn²⁺, Ni²⁺, Zn²⁺ in food contact plastic. ESI-QTOF MS analysis was performed under positive ion mode (ESI⁺) and multiple reaction monitor high resolution (MRM HR) mode. The limits of detection (LODs) of 6 metal ions range from 0.02 to 0.08 mg/kg, recoveries are 88.6%-115%, and the relative standard deviations are between 0.3% and 6.1%. Migration solutions from 24 batches of food contact plastic were tested, while 4 of them contain detectable Cu²⁺, Mn²⁺ and Zn²⁺. The proposed method is easily appliable to determine metal ions in high proportion ethanol aqueous solution without needing to remove the ethanol. It is suitable for compliance screening of cobalt, copper, manganese, zinc in migration solution from food contact plastic, and provides a valuable reference for the analysis of unknown hazardous substances from food contact plastic.