Linearity of chromatographic systems in drug analysis part III: examples of nonlinear drug assays

Abstract

Chromatography-based drug assays are generally considered to be linear, provided that the back calculated concentrations of 75% of the calibrators are within ±15% of their target values. Data meeting this criterion are not usually subject to further examination in order to evaluate the extent of any nonlinearity and whether use of a nonlinear calibration function would improve the accuracy. Examples of nonlinear behavior are presented for several chromatographic systems and most are best described by the nonlinear equation y = a + bx + cxln(x). A more critical evaluation of linearity, as presented herein, can lead to the identification of nonlinear behavior and an improvement in accuracy by use of a nonlinear calibration regression.