A fractional factorial design [31] was used to screen the main factors and to find the best conditions of acidic PFAS extraction from milk. Seven variables were selected to optimize the experimental design. The variable level of values tested for each feature was two (−1 and +1). The variable (V) were: (1) temperature of extraction solvent; (2) solvent to milk volume ratio; (3)water to milk extract volume ratio before SPE;