Drug spatial distribution imaging uses MSI to acquire mass spectral signals pixel by pixel from tissue sections (e.g., liver, kidney, brain, tumor, intestine) after administration, reconstructing the two- or three-dimensional spatial distribution of candidate compounds and their metabolites within organs. Compared with LC-MS homogenate quantification, it preserves tissue architecture and can distinguish target vs non-target regions and enrichment vs clearance regions, making it a key tool for drug metabolism/pharmacokinetics (DMPK) to move from 'overall concentration' to 'in-situ localization'.
In the application practice of the Neo-Source MSI DPI imaging source, DPI adopts desorption electrospray ionization combined with photochemical post-ionization, requiring no matrix spraying and exhibiting low ion-suppression effects, so complex biological samples can be analyzed directly; its resolution is adjustable in the 20–200 μm range, covering spatial analysis needs from organ scale to local lesions, and has been used for distribution studies of drugs and metabolites across different time points and organs, drug quantification and drug discovery.
A standard drug distribution imaging workflow includes: animal dosing and setting sampling time points → tissue harvesting and frozen embedding → serial sectioning (one part for MSI, adjacent sections for H&E or IHC validation) → point-by-point scanning on the instrument → ion image reconstruction → registration with pathological sections. Placing MSI sections alongside H&E-stained sections allows precise overlay of molecular distribution onto histological structures, answering questions such as 'does the signal-enhanced region fall exactly on the target cell band'.
The sample preparation burden deserves emphasis. Traditional matrix-assisted imaging requires uniform spraying of small-molecule matrix, which is cumbersome and whose matrix peaks interfere with low-mass signals; both Neo-Source MSI DPI and MSI LDPI feature 'no matrix spraying' and 'no matrix interference', reducing sample handling from 'half a day at best' to 'measure on demand', which is especially critical for drug screening requiring many time-point samples.
First, target-site verification: confirm whether the drug truly enters the intended tissue region rather than merely staying in blood or marginal tissue. Second, toxicity hints: detect abnormal accumulation of the drug in non-target organs (e.g., renal cortex, myocardium) to warn of potential toxicity in advance. Third, formulation and delivery evaluation: compare spatial distribution differences under different formulations, nanocarriers or administration routes. Fourth, metabolite tracking: distinguish whether the distribution of parent drug and metabolites is consistent; some active metabolites may play a key role where the parent drug does not reach.
In DPI application cases, tests on animal tissues and plant leaves showed that, in both positive and negative ion modes, compared with traditional DESI, more than a hundred additional lipids, terpenoids, flavonoids, amino acids, glycosides, and other secondary metabolites could be detected, with overall metabolite signal intensity enhanced by 1–3 orders of magnitude; this sensitivity leap also benefits the spatial detection of low-abundance drugs and metabolites.
MSI provides 'molecular species + spatial coordinates', but does not directly give protein sequences or gene expression. Therefore drug distribution studies are often combined with immunofluorescence, H&E and in-situ hybridization: using MSI to see small-molecule and metabolite distributions and IHC to see target protein locations, forming a more complete mechanistic explanation after registration.
From an engineering deployment perspective, the two Neo-Source imaging sources are compatible with mainstream mass spectrometers from Agilent, AB SCIEX and Thermo (e.g., MSI DPI-25A/25S/25T), and provide a self-developed titanium-alloy ion transfer tube that does not damage the sample at the front end and is detachable for cleaning, enabling teams to stably move drug distribution imaging from research projects into quality-control and screening production lines.
To obtain detailed specifications, compatible models, or a quotation for the MSI LDPI / DPI full series imaging ion sources, visit the Neo-Source official website, or contact the official team for compatibility advice tailored to your mass spectrometer (Agilent / SCIEX / Thermo and other mainstream MS).