The MSPIRE research that I have engaged in involves the development of matrix-assisted laser desorption/ionization tandem mass spectrometric (MALDI-MSⁿ) methods for the quantitation of cocaine and its metabolites in postmortem brain tissue of a chronic human cocaine user. It has been shown that tandem mass spectrometry (MS² and MS³) dramatically increases selectivity, which is critical for differentiating analyte ions from background ions such as matrix clusters and endogenous compounds found in brain tissue. It has also been shown that the use of internal standards corrects for signal variability during quantitative MALDI, as shown in the figure below, which can be caused by inhomogenous crystal formation, inconsistent sample preparation, and laser shot-to-shot variability. The MALDI-MSⁿ method allows for a single MS³ experiment that uses a wide isolation window to isolate both analyte and internal standard target ions. This method provides dramatically improved precision (approximately 10-20 times reduction in percent relative standard deviation (%RSD)) for quantitative imaging studies compared to using two alternating MS³ experiments that separately isolate the target analyte and internal standard ions. The method has also been extended to use stored-waveform inverse-Fourier transform (SWIFT) waveforms to isolate as many as twelve different specific ions for MS/MS.

Figure. Improvement in precision in quantitative MALDI-MS analysis by using an isotopically-labeled internal standard