Quantitative liquid chromatography/mass spectrometry for the analysis of microdialysates

Microdialysis (MD) is an in vivo sampling technique used to investigate biochemical events in the extracellular fluid of animal and human tissues. MD produces protein- and cell-free, aqueous samples which can be analyzed without further sample clean-up. Liquid chromatography coupled to tandem mass spectrometry (LC–MS/MS) is a sensitive and selective analysis technique which is suitable to quantify low concentrated target analytes in microdialysates. This paper reviews the LC–MS/MS methods which are described for the quantification of endogenous molecules, such as neurotransmitters and peptides, and of exogenous molecules, such as drugs, in microdialysates.Since miniaturization of the LC–MS/MS methods is the key to obtain maximal sensitivity of the analytical technique, this feature is discussed in the paper. In addition, critical issues related to the quantification of low concentrated molecules in microdialysates are described such as the presence of matrix effects, the low MD efficiency and the sticking of, for instance, neuropeptides.