Perfluorooctane sulfonate (PFOS) precursors can be metabolized enantioselectively: principle for a new PFOS source...

Perfluorooctane sulfonate (PFOS) is the most prominent perfluoroalkyl substance found in the serum of humans and wildlife, yet the major routes by which exposure occurs are not clear. An important issue facing both the scientific and chemical regulatory communities is the extent to which PFOS concentrations in biota are attributable to direct exposure versus metabolism of PFOS-precursors (higher molecular weight derivatives that can be biotransformed to PFOS). Given that certain branched PFOS-precursors are chiral, we hypothesized that nonracemic proportions of PFOS isomers in biological samples could be used as a marker of significant exposure to PFOS-precursors. In this proof-of-principle study we examined the enantiomer-specific biotransformation of a high-purity model PFOS-precursor isomer: C(6)F(13)C*F(CF(3))SO(2)N(H)CH(2)(C(6)H(4))OCH(3) (named 1m-PreFOS hereafter, and whereby * indicates the chiral carbon center). A method for the enantiospecific separation of a compound with a long perfluoroalkyl chain and a chiral center was developed and applied to evaluate the enantioselectivity of 1m-PreFOS biotransformation in human liver microsomes. Gradient elution in reversed-phase mode on a Chiralpak IC column permitted the near-baseline separation of the two enantiomers (E1 and E2, nomenclature based on retention order) in 65 min. Microsome incubations demonstrated that E1 and E2 were metabolized at significantly different rates; k(E1) = 6.5(+/-0.3) x 10(-2) min(-1) (half-life = 10.6 min) and k(E2) = 5.2(+/-0.3) x 10(-2) min(-1) (half-life = 13.3 min), respectively. These results suggest that tracking of PFOS exposure sources by enantiomeric fractionation is feasible, and that new analytical methods for the enantioselective analysis of PFOS isomers in human and environmental samples should be developed.