Quantitative DESI mass spectrometry imaging of lung distribution of inhaled drug

Abstract

Clinically, the particle size and size distribution of inhaled drug play an extremely important role in airway drug deposition and therapeutic outcome. It is necessary to fully understand the spatial distribution of inhaled drugs, which will contribute to the drug development. However, all spatial information is lost in the sample processing of conventional pharmacokinetic study. Mass spectrometry imaging (MSI) is a powerful tool for visualization of spatial localization of biological molecules or metabolites in tissue section without the procedure of any tagging or labeling chemistry. In this study, we have established a quantitative DESI imaging to detect the drug concentration in lung and the results of two administration methods (inhalation and oral) were compared. In addition, the spatial localization of inhaled drug was also visualized, and the in vitro in vivo correlations (IVIVCs) of lung distribution of inhaled drug were explored. Our results indicated that the spatial localization of drug aerosol delivered by the Pari nebulizer at the lung parenchyma has a tendency to be higher than the results obtained by Omron nebulizer. The signal intensity in the primary bronchi by Omron nebulizer was significantly higher than that result of Pari nebulizer. In vitro particle characterization, the ratio of small particles produced by the Pari nebulizer is higher than the results of Omron nebulizer. The in vivo and in vitro results show a consistency. The quantitative DESI-MSI is a potential tool for analysis and quantify the drug concentration in lung tissue.