In the drug candidate qualification process, pharmacokinetic screening, metabolic stability with metabolite identification, enzyme induction and inhibition, and excretion studies play a major role. For tissue-distribution studies, whole-body autoradiography (WBA) is commonly employed. It has the advantage of being quantitative in nature but suffers from several disadvantages.
In particular, WBA requires the use of radioactive compounds and turnaround times can be up to several weeks. DESI-MS imaging presents an alternative approach for tissue-distribution studies by allowing for direct analysis and imaging of intact tissue sections without the use of radio-active labels. Sample turnaround times of just a few hours are another benefit. A typical mass spectrum recorded on a 10 µm thick rat-lung tissue section is presented in Figure 2a.
The lower m/z range represents the region where most drugs and metabolites are detected. The upper portion of the m/z range represents the lipid and peptide region. Figure 2b shows the DESI mass spectrum in the lower m/z range of the lung tissue. Of particular interest are the peaks at m/z 327 and m/z 313, which represent the presence of the drug clozapine and its metabolite, desmethylclozapine, respectively. Among other possibilities, the remaining peaks include endogenous small molecules carrying a positive charge.
Figure 3 shows the optical image and the DESI image from a rat brain section taken from an animal that had been dosed at 50 mg/kg of clozapine via oral gavage and the brain removed 30 minutes post-dose. The tissue was imaged in the MS/MS mode, and the DESI product ion spectra resulting from fragmentation of clozapine at m/z 327.1 (M+H)+ were recorded with a pixel size of 245 µm x 245 µm.
The Omni Spray 2D Ion Source has advantages and presents possibilities for the drug discovery scientists’ toolbox. Utilizing the Omni Spray 2D Ion Source for tissue-distribution studies has the potential to eliminate the need for expensive synthetic molecules while increasing sample throughput. DESI has also been used for exploring the impact of drugs and disease on endogenous compounds, revealing counterfeit drug formulations, and identifying thin layer chromatography spots. In addition, the technology has shown potential in pharmacokinetic screening and cleaning validation.