Relative response ratios for dual-isotope measurements via coelution and GC/MS

Dual-isotope internal standard measurements by gas chromatography (GC) (MS) mass spectroscopy which mimic isotope dilution may suffer from non-linear response relations, irreproducibilities or unduly large uncertainties because of variations in ionization efficiencies for the respective isotopic forms in the MS source. Such variations may sometimes be avoided via extensive pretreatments, high resolution GC separations and careful control of instrumental parameters. However, an alternative approach is feasible which instead exploits advantages of decreasing GC resolution. By forcing both forms of each analyte to coelute, their relative ionization efficiencies in the MS source should be nearly constant, thereby effectively allowing for constant relative sensitivities over several orders of magnitude in concentration. Thus, constant relative response ratios, required for internal standard calculations, may be attained as a consequence of dramatically lowered GC resolution. Coelution results described herein show linear relative sensitivity relations over much broader ranges than those observed for corresponding conventional calibrations with separated components. Coelution methods for dual-isotope GC/MS determinations are compatible with internal standard calculations and thereby offer a powerful alternative to the conventional approach of requiring expensive and labor-intensive additional pretreatrments and separations to assure resolution of measured eluates. (author)