Rapid Screening for Hazardous Substances with Regulatory Differences in Milk Between Countries Using Ultra-High Performance Liquid Chromatography Ion Mobility Quadrupole Time-of-Flight Mass Spectrometry.

Regulatory heterogeneity on the maximum residue levels (MRLs) of hazardous substances for food is identified as a challenge of trade between countries. To balance the import and export trade of milk, a high-throughput determination method was established for hazardous substances with regulatory differences. In this paper, we investigated 462 hazardous substances with different MRLs for food based on different countries' regulations, involving pesticides, veterinary drugs, and some toxins. A mass database was established for these compounds including the basic information, retention time, collision cross section, parent ion, and product ions with ultra-high performance liquid chromatography ion mobility quadrupole time-of-flight mass spectrometry (UPLC-IM-QTOFMS). After that, the sample preparation for milk, including extraction solvents and purified sorbents, was optimized by selecting 274 hazardous compounds as the representative compounds. Acetonitrile/methanol (9:1, v/v) containing 1% acetic acid was used for extracting, and 50 mg EMR and 50 mg PSA were used for purifying the target substances in milk. Then, the methodology was evaluated by spiking the compounds in real milk. The experiment was conducted by matrix calibration, and the results displayed that most compounds had good linearity within their linear ranges (R(2) > 0.99). The recovery ranged from 61.8% to 119.7% at three spiking levels, with RSDs between 1.1% and 20.2%. The limits of quantitation of target compounds in milk ranged from 1 to 10 μg/kg. This could meet the MRL requirements among different countries. All the results demonstrated this determination technology was a fast, sensitive, and accurate method for screening hazardous substance.