Abstract
Mass spectrometric imaging (MSI) is an
analytical technique used to determine the distribution of
individual analytes within a given sample. A wide array of
analytes and samples can be investigated by MSI, including
drug distribution in rats, lipid analysis from brain tissue,
protein differentiation in tumors, and plant metabolite
distributions. Matrix-assisted laser desorption/ionization
(MALDI) is a soft ionization technique capable of desorbing
and ionizing a large range of compounds, and it is the most
common ionization source used in MSI. MALDI mass
spectrometry (MS) is generally considered to be a qualitative
analytical technique because of significant ion-signal variability. Consequently, MSI is also thought to be a qualitative technique
because of the quantitative limitations of MALDI coupled with the homogeneity of tissue sections inherent in an MSI
experiment. Thus, conclusions based on MS images are often limited by the inability to correlate ion signal increases with actual
concentration increases. Here, we report a quantitative MSI method for the analysis of cocaine (COC) from brain tissue using a
deuterated internal standard (COC-d3) combined with wide-isolation MS/MS for analysis of the tissue extracts with scan-by-scan
COC-to-COC-d3 normalization. This resulted in significant improvements in signal reproducibility and calibration curve
linearity. Quantitative results from the MSI experiments were compared with quantitative results from liquid chromatography
(LC)-MS/MS results from brain tissue extracts. Two different quantitative MSI techniques (standard addition and external
calibration) produced quantitative results comparable to LC-MS/MS data. Tissue extracts were also analyzed by MALDI wideisolation
MS/MS, and quantitative results were nearly identical to those from LC-MS/MS. These results clearly demonstrate the
necessity for an internal standard for quantitative MSI experiments.
Original language | English |
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Pages (from-to) | 1081-1089 |
Number of pages | 9 |
Journal | Analytical Chemistry |
Volume | 85 |
DOIs | |
Publication status | Published - 2013 |