Elucidating Gender-Specific Distribution of Imipramine, Chloroquine, and Their Metabolites in Mice Kidney Tissues through AP-MALDI-MSI.

Knowledge of gender-specific drug distributions in different organs are of great importance for personalized medicine and reducing toxicity. However, such drug distributions have not been well studied. In this study, we investigated potential differences in the distribution of imipramine and chloroquine, as well as their metabolites, between male and female kidneys. Kidneys were collected from mice treated with imipramine or chloroquine and then subjected to atmospheric pressure matrix-assisted laser desorption ionization-mass spectrometry imaging (AP-MALDI-MSI). We observed differential distributions of the drugs and their metabolites between male and female kidneys. Imipramine showed prominent distributions in the cortex and medulla in male and female kidneys, respectively. Desipramine, one of the metabolites of imipramine, showed significantly higher (*** p < 0.001) distributions in the medulla of the male kidney compared to that of the female kidney. Chloroquine and its metabolites were accumulated in the pelvis of both male and female kidneys. Interestingly, they showed a characteristic distribution in the medulla of the female kidney, while almost no distributions were observed in the same areas of the male kidney. For the first time, our study revealed that the distributions of imipramine, chloroquine, and their metabolites were different in male and female kidneys.

Low-Temperature Plasma Pretreatment Enhanced Cholesterol Detection in Brain by Desorption Electrospray Ionization-Mass Spectrometry Imaging.

Cholesterol is a primary lipid molecule in the brain that contains one-fourth of the total body cholesterol. Abnormal cholesterol homeostasis is associated with neurodegenerative disorders. Mass spectrometry imaging (MSI) technique is a powerful tool for studying lipidomics and metabolomics. Among the MSI techniques, desorption electrospray ionization-MSI (DESI-MSI) has been used advantageously to study brain lipidomics due to its soft and ambient ionization nature. However, brain cholesterol is poorly ionized. To this end, we have developed a new method for detecting brain cholesterol by DESI-MSI using low-temperature plasma (LTP) pretreatment as an ionization enhancement. In this method, the brain sections were treated with LTP for 1 and 2 min prior to DESI-MSI analyses. Interestingly, the MS signal intensity of cholesterol (at m/z 369.35 [M + H - H2O]+) was more than 2-fold higher in the 1 min LTP-treated brain section compared to the untreated section. In addition, we detected cholesterol, more specifically excluding isomers by targeted-DESI-MSI in multiple reaction monitoring (MRM) mode and similar results were observed: the signal intensity of each cholesterol transition (m/z 369.4 → 95.1, 109.1, 135.1, 147.1, and 161.1) was increased by more than 2-fold due to 1 min LTP treatment. Cholesterol showed characteristic distributions in the fiber tract region, including the corpus callosum and anterior commissure, anterior part of the brain where LTP markedly (p < 0.001) enhanced the cholesterol intensity. In addition, the distributions of some unknown analytes were exclusively detected in the LTP-treated section. Our study revealed LTP pretreatment as a potential strategy to ionize molecules that show poor ionization efficiency in the MSI technique.