Imaging mass spectrometry matrix application methods

The preparation of samples for mass spectrometric analysis almost always requires recovery of the analyte from a matrix, often followed by further preparative steps prior to introduction of the sample into the ion source. Such destructive processes are unacceptable when the objective is to determine the specific location of a particular compound within a biological sample, e.g., the location of a certain lipid in a tissue, and led to the development of imaging mass spectrometry with MALDI as the ionization method, although DESI is also applicable. 

In addition to some early applications in bioanalysis, ambient ionization mass spectrometry has been used as an imaging tool to study drug distribution in tissue sections. Most of the work reported so far involved the use of DESI as the ambient ionization method. Compared to other mass spectrometry-based tissue imaging techniques such as MALDI and SIMS, DESI allows tissue samples to be analyzed under ambient conditions without sample preparation, which simplifies the procedure and prevents the redistribution of analytes during matrix deposition. A major drawback of DESI as an imaging tool is its relatively low spatial resolution (typically 250 pm) and therefore cannot be used for cellular or subcellular imaging. 

An example of the application of the wide isolation window in tandem mass spectrometry is the detection and quantitative imaging of cocaine in postmortem human brain tissue (Reich et al., 2008 Reich et al., 2010). In this instance, it was determined necessary to develop an MS wide isolation window method because of interfering background ions. Cocaine detected in brain tissue was confirmed by matching six MS product ions with those from a cocaine standard. For the quantitation of cocaine analyzed from the tissue, the trideuterated ( Hs) internal standard was spiked beneath the tissue at known concentrations before matrix application to develop a calibration curve. The MS wide isolation method was then employed for the analysis of cocaine and cocaine-fi 3. Cocaine was analyzed successfully and quantified using this approach. 

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