Taming super non-linearity: Quantification using new models of charged aerosol detectors

The Charged Aerosol Detector is widely employed in modern analytical laboratories, especially within the pharmaceutical industry, due to its broad applicability. However, a significant limitation of the CAD lies in its inherent nonlinearity, traditionally addressed through mathematical transformations (power functions) aimed at achieving linear behaviour for quantification. Recent studies, however, challenge the validity of such linearization, proposing that the CAD operates under a fundamentally nonlinear model that cannot be globally linearized. This study evaluates the practical impact of these new models on the quantification of routine pharmaceutical products. When traditional global linearization and single-point calibration were applied, quantification discrepancies of up to 203% were observed between CAD and UV detection. In contrast, applying the newer super nonlinear model with appropriate processing methods reduced this discrepancy to as low as 3%. These findings suggest that the super nonlinear model more accurately represents CAD behaviour, providing consistent results across different analytical approaches. This highlights the importance of selecting suitable quantification strategies when using the CAD to ensure accurate and reliable assay outcomes. • Power functions required to linearize calibration curves changed as a function of concentration. • Global power-function linearization appeared statistically valid yet produced large discrepancies between CAD vs UV quantification of the same sample. • Accurate CAD quantification required local linearization or numerical inversion of the super-nonlinear CAD response model. • Super-nonlinear data processing yielded close agreement with UV assays for routine pharmaceutical products.