Covalent binding of organophosphorothioates to albumin: a new perspective for OP-pesticide biomonitoring?

We here report on the covalent binding of various organophosphorothioate (OPT) pesticides to albumin at in vitro exposure levels that did not give rise to butyrylcholinesterase inhibition. Adduct formation occurred at the Tyr-411 residue of albumin, as was firmly corroborated by LC-tandem MS analysis of a pepsin digest of OPT-modified albumin. It cannot be excluded that other (tyrosine) residues become modified as well. A convenient method for mass spectrometric determination of the OPT tyrosine adduct has also been developed based on the pronase digestion of albumin and subsequent LC-tandem MS analysis of the digest. The resulting tyrosine phosphorothioate ester displayed favorable chromatographic and mass spectrometric properties for sensitive analysis. In vitro exposure levels of parathion and chlorpyrifos down to 1 microM could readily be assessed. The remarkable affinity of OPTs for albumin opens the way for a more complete assessment of OP pesticide exposure.