Quantification of Drugs in Brain Samples

Due to the lack of certified reference material, a reliable quantification in complex postmortem matrices can only be performed either by the addition of isotope-labelled standards or by the standard addition method. Although standard addition is a basic quantification procedure, its practical implementation is challenging, and a highly reproducible extraction method is essential. Therefore, an automated solid-phase extraction screening procedure was validated in respect to the specific requirements in postmortem analyses, using pig brain fortified with nine compounds to represent a realistic postmortem setting. The validation parameters linearity, repeatability, reproducibility and recovery were selected to test the method's 'fitness for purpose'. All obtained results were satisfying, although the method was not optimized for the selected compounds. Therefore, this validated method could be used for further standard addition experiments to evaluate the importance of the initial estimated concentration for the calculation of concentrations to set up the calibration curve. We could show that the best results were obtained when the estimated concentration was close to the real concentration. In case of a deviation, an underestimation is more favorable than an overestimation.