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Use of Calculated Physicochemical Properties to Enhance Quantitative Response When Using Charged Aerosol Detection Max W. Robinson,*,† Alan P. Hill, Simon A. Readshaw, John C. Hollerton, Richard J. Upton, Sean M. Lynn, Steve C. Besley, and Bob J. Boughtflower GlaxoSmithKline, Gunnels Wood Road, Stevenage, SG1 2NY, United Kingdom of Great Britain and Northern Ireland S Supporting Information *
ABSTRACT: Universal quantitative detection without the need for analyte reference standards would offer substantial benefits in many areas of analytical science. The quantitative capability of high-performance liquid chromatography (HPLC) with charged aerosol detection (CAD) was investigated for 50 compounds with a wide range of physical and chemical properties. It is widely believed that CAD is a mass detector. Quantification of the 50 compounds using a generic calibrant and mass calibration achieved an average error of 11.4% relative to 1H NMR. Correction factors are proposed that estimate the relative surface area of particles in the detector, taking into account the effects of the density and charge of analytes. Performing these corrections and quantifying with surface area calibration, rather than mass, shows considerably improved linearity and uniformity of detection, reducing the average error relative to 1H NMR to 7.1%. The accuracy of CAD quantification was most significantly improved for highly dense compounds, with traditional mass calibration showing an average error of 34.7% and the newly proposed surface area calibration showing an average error of 5.8%.
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method for qualitative analysis. However, quantitative applications still require analyte specific calibrants.5−7 Chemiluminescent nitrogen detection (CLND) has been successfully deployed as a quantitative detector; however, its wider deployment has been hampered by its requirement for analytes to contain nitrogen.8 It also requires high levels of maintenance and is not compatible with mobile phase components containing nitrogen.5 Perhaps the greatest promise for a universal quantitative detector lies within the group of “aerosol detectors” which include evaporative light-scattering (ELSD) and Corona charged aerosol (CAD) detectors. ELSD was the first of these detectors to be developed but has relatively low sensitivity, is incapable of detecting volatile compounds (a fundamental limitation of any evaporative detector), and has a more variable compound response that is also dependent on the mobile phase composition.8−10 CAD is reported to have the greater dynamic range and sensitivity.5 CAD also gives a more universal response between analytes, with the most recent versions reported to have an interanalyte response across a broad range of compounds on the order of
