Conclusions:

The LTQ with MALDI source makes for an outstanding platform for the study of drug distribution and its metabolites directly off tissue. The sensitivity of the linear ion trap, in particular, allows for an MS/MS spectrum with less than 10 laser shots at each location.

MALDI matrix, solvent selection, and the pH at which the drug is most soluble are critical parameters in the analysis of tissue by MALDI. The matrix should not have interfering peaks in the m/z of interest (both MS and MS/MS). One has to ensure that matrix application is efficient in its extraction of the analyte.

Three of the characteristic erlotinib fragment ions were found in treated pancreas tumors by CID of both parent drug and metabolite in two different matrices (not all spectra shown). Significantly less of the m/z 278 and m/z 336 fragment ions were found in the untreated specimens as compared with the erlotinib-treated ones.

MALDI as conducted in this study, without the use of isotopic labels or internal standards, is not considered a quantitative technique. However, data processing for both treated and untreated tissues were kept consistent and normalized to the same intensity scale. A relative comparison and visualization of the different distribution and amounts of measurable drug between the two was therefore possible. The use of tissue replicates would be recommended for future studies.

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