A novel approach to evaluate the extent and the effect of cross-contribution to the intensity of ions designating the analyte and the internal standard in quantitative GC-MS analysis

In gas chromatography-mass spectrometry methods of analysis adopting the analyte’s isotopic analog as the internal standard (IS), the cross-contribution (CC) phenomenon—contribution of IS to the intensities of the ions designating the analyte, and vice versa—has been demonstrated to affect the quantitation data. A novel approach based on the deviations of the empirically observed concentrations of a set of standards was developed to assess the accuracy of the empirically derived CC data. This approach demonstrated that normalization of ion intensities derived from the analyte and the IS generates reliable CC data. It further demonstrated that an ion-pair (designating the analyte and the IS) with ∼5% or higher CC will result in a very limited linear calibration range.