Use of Calculated Physicochemical Properties to Enhance Quantitative Response When Using Charged Aerosol Detection

Area of Science:

• Analytical Chemistry
• Chromatography
• Spectroscopy

Background:

• Universal quantitative detection without analyte reference standards is highly desirable in analytical science.
• Charged Aerosol Detection (CAD) is commonly perceived as a mass-dependent detector.
• Existing methods often require specific calibrants for accurate quantification.

Purpose of the Study:

• To investigate the quantitative capabilities of high-performance liquid chromatography (HPLC) with charged aerosol detection (CAD) for diverse compounds.
• To evaluate the accuracy of mass calibration versus a proposed surface area calibration method.
• To develop correction factors for improved CAD quantification.

Main Methods:

• Investigated 50 compounds with varied physical and chemical properties using HPLC-CAD.
• Performed quantification using generic calibrant with mass calibration.
• Developed and applied correction factors based on analyte particle surface area, density, and charge.
• Quantified using surface area calibration and compared results to 1H NMR.

Main Results:

• Mass calibration yielded an average error of 11.4% relative to 1H NMR.
• Surface area calibration reduced the average error to 7.1%.
• Accuracy for dense compounds improved dramatically: mass calibration error of 34.7% reduced to 5.8% with surface area calibration.

Conclusions:

• HPLC-CAD can achieve universal quantitative detection without analyte reference standards.
• Surface area calibration offers superior accuracy and linearity compared to traditional mass calibration for HPLC-CAD.
• Proposed correction factors enhance the reliability of CAD for quantifying compounds with diverse properties, especially dense analytes.