The reliable detection and quantitation of low-to-medium polarity persistent organic pollutants in food or environmental samples as required by governmental regulations can be readily made via GC-APCI-QTOF MS. High sensitivity is supported by the soft ionization characteristics of the APCI source, preserving molecular ions. Using QTOF MS for the detection and subsequent fragmentation of these ions provides high resolution, high value data for broad screening workflows. The analytical performance of this workflow is demonstrated to meet specific US EPA criteria both in standard solutions and in a complex fish tissue matrix.