Targeted Drug and Metabolite Imaging: Desorption Electrospray Ionization Combined with Triple Quadrupole Mass Spectrometry

Abstract

Mass spectrometry imaging (MSI) has proven to be a valuable tool for drug and metabolite imaging in pharmaceutical toxicology studies and can reveal, for example, accumulation of drug candidates in early drug development. However, the lack of sample cleanup and chromatographic separation can hamper the analysis due to isobaric interferences. Multiple reaction monitoring (MRM) uses unique precursor ion-product ion transitions to add specificity which leads to higher selectivity. Here, we present a targeted imaging platform where desorption electrospray ionization is combined with a triple quadrupole (QqQ) system to perform MRM imaging. The platform was applied to visualize (i) lipids in mouse brain tissue sections and (ii) a drug candidate and metabolite in canine liver tissue. All QqQ modes were investigated to show the increased detection time provided by MRM as well as the possibility to perform dual polarity imaging. This is very beneficial for lipid imaging because some phospholipid classes ionize in opposite polarity (e.g., phosphatidylcholine/sphingomyelin in positive ion mode and phosphatidylserine/phosphatidylethanolamine in negative ion mode). Drug and metabolite images were obtained to show its strength in drug distribution studies. Multiple MRM transitions were used to confirm the local presence and selective detection of pharmaceutical compounds.

Enhanced Sensitivity Using MALDI Imaging Coupled with Laser Postionization (MALDI-2) for Pharmaceutical Research

“…Recently, compound A (the exact identity and mass cannot be provided due to confidentiality reasons) was visualized in canine liver tissue using desorption electrospray ionization (DESI) imaging and multiple reaction monitoring (MRM). 45 Using both MALDI and MALDI-2, we first screened a ∼ 1 cm 2 of tissue obtained from a treated dog which developed lesions. MALDI revealed a very low signal intensity for the drug compound (for the expected [M + H] + ion at m / z 502 and was not detected at all for [M + Na] + ion) after inspection of the averaged spectra across the analyzed tissue regions.…”

Three dimensional secondary ion mass spectrometry imaging (3D-SIMS) ofAedes aegyptiovarian follicles

“…[3,4] However, depending on the biological question, the chemical mapping of the lipid distribution in biological systems using mass spectrometry imaging (MSI) techniques is mandatory. For example, liquid based junctions, jets and micro-junctions (i.e., liquid extraction surface analysis, or LESA), [5,6] desorption electrospray ionization (DESI), [7,8] and nanospray desorption electrospray ionization (nano-DESI) [9] can provide lipid chemical maps with spatial resolution down to ~600 μm, ~50 μm, [10,11] and ~10 μm, [12] respectively, under ambient conditions and without the need of any surface treatment. Other MSI techniques using laser sources can provide a higher spatial resolution (10-50 μm or down to few μm using special arrangements [13]) at ambient or vacuum conditions, but typically require the coating of the biological surfaces with a matrix (i.e., MALDI [14][15][16]); the matrix choice and application method determine the selectivity of analytes and the crystal size can become the limiting factor of the spatial resolution [16,17].…”

Imaging Isomers on a Biological Surface: A Review

“…Here, multiple compounds can be targeted simultaneously, and since MRM is speci c for the precursor and product ions, it can be used to separate isobaric compounds with improved sensitivity. 30) Aside from ESI-based ionization methods, also MALDI-MRM-MS has shown to be a feasible alternative method for sensitive and selective analysis. 31,32) It is also possible to use TOF-MS systems for tandem-MS, namely with an axial TOF-TOF con guration.…”