Matrix effect marker for multianalyte analysis by LC–MS/MS in biological samples

► The prevalence of acute matrix effect in the analysis of corticoids by LC–MS is studied. ► A novel and selective marker to identify cases with acute matrix effect is introduced. ► A non matrix affected LC–MS based method for the analysis of corticoids in doping control is proposed. Matrix effects (ion suppression/enhancement) are a well-observed phenomenon in analyses of biological matrices by high-performance liquid chromatography–mass spectrometry (LC–MS). However, few simple solutions for detecting and minimizing these adverse effects have been described so far in multianalyte analysis, especially in the field of doping control. This study describes an exhaustive characterization of matrix effects in one hundred urine samples fortified with 41 analytes (glucocorticoids and diuretics). It introduces a novel marker to identify samples in which the reliability of the results is compromised because of acute ion suppression. This new strategy strengthens the rigor of the analysis for screening purposes. Once the matrix effect is identified, a selective sample preparation is introduced to minimize the adverse ion suppression effect. That selective extraction together with the use of a deuterated internal standard permits enhancing the ruggedness of the estimation of glucocorticoid concentration in urine.