In the present study, a new extraction method based on acid digestion and SPE clean-up (Oasis Wax) was developed for measuring four PFR metabolites (i.e. dibutyl phosphate (DBP), diphenyl phosphate (DPhP), bis(1,3-dichloro-2-propyl)phosphate (BDCPP) and bis(2-butoxy ethyl) phosphate (BBEP)) in hair and nails. The method optimization was done according to a combinatorial design (Taguchi) where several parameters were efficiently optimized. Precision was lower for hair than for nails (RSD % 18 and 28%). Recoveries were >74%. High DBP levels in procedural blanks were traced back to the use of SPE cartridges. Therefore a new SPE pre-treatment was tested, reducing significantly DBP levels (