Soybean is one of the most commonly allergenic foods in the U.S., and the ubiquity and variety of commercial soy ingredients in the food industry make it a challenging allergen to avoid. The processing methods used to produce soy-derived ingredients result in protein modifications that often substantially impact detection and quantification with commonly used antibody-based methods. This study aimed to develop a mass spectrometry (MS)-based method capable of quantifying commercially processed soy ingredients in food matrices. A quantification strategy using external standards with internal calibrants was developed and evaluated, resulting in the ultimate use of a matrix-independent standard curve of non-roasted soy flour with milk proteins as carrier proteins. The method performance was evaluated by quantifying six soy-derived ingredients in incurred food matrices. Out of the twelve ingredient-matrix combinations with 10 ppm incurred total soy protein, eight had maximum recoveries between 60-120%. Compared with three commercial ELISA kits, the MS method showed a substantial advantage in quantifying the highly processed soy proteins in food matrices.