Trade of food products continues to increase globally,which is leading to greater food safety concerns for pesticide residues and environmental contaminants in the commodities.This leads to great demands on methods to achieve high quality results for wide scope of ultra-trace contaminants in diverse,complicated food matrices.In this study,different approaches for sample preparation,cleaning-up and GC/LC-MSMS detection were investigated in the establishments of high sample through-put multi-residue analytical method for about 250 pesticides and environmental contaminants in fatty foods,including meats(beef,chicken,and pork),fish,and avocado.The modified QuEChERS(quick,easy,cheap,effective,rugged,and safe)method was applied for the streamlined sample preparation,and the volatile salt NH4CO2H was used instead of NaCl to reduce the GC system maintenance.The Filter-in-vial d-SPE approach with different sorbents was conducted to reduce a centrifugation step and achieved sufficient cleanup.The performance of a novel product EMR-Lipid(Enhanced matrix removal of Lipid)was also investigated and it showed excellent removal efficiency of lipids and other co-extractives in fatty foods.The application of an automated mini-SPE cleanup using the Instrumental Top Sample Preparation(ITSP)system could save labor and improve precision.In high-throughput analyses of the GC-and LC-amenable analytes,both the low-pressure(LP)GC-MS/MS and UHPLC-MS/MS only took 10 min for each run while providing increased sample capacity,sensitivity,and ruggedness.The method validation results showed that about 80%(about 200)of the analytes achieved satisfactory recoveries(70-120%)with RSD<20%in meats samples.These approaches provide alternatives in establishment of high through-put multi-residue analysis methods of pesticides and environmental contaminants in complex food matrices.