Determination of endogenous metabolites in intact tissue in clinical settings using coated blade spray mass spectrometry (CBS-MS)

Abstract

Fast diagnosis can be crucial in patients' diagnosis and treatment. Thus, an assessment of biomarker drugs, or their metabolite levels, is necessary. The level of selected substances can be rapidly determined by directly introducing samples or their components into the mass spectrometer, often omitting the sample separation step. However, this approach can lead to increased matrix effects and challenges in identifying substance isoforms. Another problem can be related to the analysis of tissue. The coated blade spray (CBS) technique, based on solid-phase microextraction (SPME), enables sample cleanup and separation based on the affinity between analytes and sorbent. The probe is a sword-shaped blade coated with sorbent at the tip. The sampling can be conducted by inserting the probe into the tissue for a particular time. During this time, analytes can be extracted without actual tissue consumption; for that reason, the technology is also known as a chemical biopsy. Then, the probe is installed in the interface on a mass spectrometer ion source. A drop of desorption solvent is added on the probe's surface, and then a high voltage is applied, facilitating efficient ionization and detection of extracted analytes. This technology enables fast and simple detection of a wide range of analytes. Moreover, it is characterized by high environmental safety. The protocol presented herein includes the best practices for CBS in intact tissue analysis. However some comments can also be applied to liquid sample analysis.