A review of sample preparation methods for quantitation of small-molecule analytes in brain tissue by liquid chromatography tandem mass spectrometry (LC-MS/MS)

Concentration measurements are one of the most important and fundamental approaches in preclinical and clinical studies of small-molecule drugs, metabolites and biomarkers, since information about the absorption (drug), synthesis (biomarker), distribution, metabolism and elimination can be obtained by determining the concentrations of target analytes in biological fluids or tissue samples. Among all the bioanalytical techniques, liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) has been widely used, due to its high sensitivity, selectivity and reproducibility. Attention has been paid to the quantitation of small-molecule analytes in brain tissue samples by LC-MS/MS, because the important information about brain concentrations obtained via such studies can be used to interpret the distribution and function of target chemicals in the central nervous system (CNS). In order to be analyzed by LC-MS/MS, brain tissue samples need to be properly obtained and carefully prepared into an LC-MS/MS compatible form. The choice made here will which greatly influence the sensitivity and robustness of the method. As a result of the vital function and complex composition of brain tissue, sample collection and preparation can be very challenging. In this review, we summarize the current techniques for the collection and preparation of brain tissue samples, which can be used as a reference for future method development for quantitation of small-molecule analytes by LC-MS/MS.