An instrumental method should detect POEA homologues and metabolites. An initial obstacle is that analytical standards for native or radiolabeled individual homologues or their mixtures are not available. There is also a lack of stable-isotope-labeled POEA homologues to use as internal standards in bioassays. Although not ideal, standards of homologues are often used for mass spectrometric (MS) quantitation, as they are assumed to have similar MS response factors and chromatographic behavior. Quantification accuracy suffers when calibration curves are based on "total" quantities rather than individual homologues. Internal standards are essential to avoid or correct for analyte concentration losses during sample pre-treatment, injection, chromatographic separation, and mass spectrometric detection. Reduction of matrix interference with chromatographic efficiency and MS detection is necessary to provide increased sensitivity for measuring biologically relevant concentrations. This requires adequate sample cleanup and extraction to preconcentrate biomarkers.