Publications by authors named "Mark T Bokhart"

A quantitative mass spectrometry imaging (QMSI) method for absolute quantification of glutathione (GSH) in healthy and cancerous hen ovarian tissues using infrared matrix-assisted laser desorption electrospray ionization (IR-MALDESI) is presented. Using this technique, the ion abundance of GSH was normalized to that of a structural analogue, which was sprayed on the slide prior to mounting the tissue sections. This normalization strategy significantly improved the voxel-to-voxel variability; the variability is attributed to the overall ionization process.

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A major update to the mass spectrometry imaging (MSI) software MSiReader is presented, offering a multitude of newly added features critical to MSI analyses. MSiReader is a free, open-source, and vendor-neutral software written in the MATLAB platform and is capable of analyzing most common MSI data formats. A standalone version of the software, which does not require a MATLAB license, is also distributed.

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High spatial resolution in mass spectrometry imaging (MSI) is crucial to understanding the biology dictated by molecular distributions in complex tissue systems. Here, we present MSI using infrared matrix-assisted laser desorption electrospray ionization (IR-MALDESI) at 50 μm resolution. An adjustable iris, beam expander, and an aspherical focusing lens were used to reduce tissue ablation diameters for MSI at high resolution.

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Ambient ionization sources for mass spectrometry (MS) have been the subject of much interest in the past decade. Matrix-assisted laser desorption electrospray ionization (MALDESI) is an example of such methods, where features of matrix-assisted laser desorption/ionization (MALDI) (e.g.

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Adherence to a drug regimen can be a strong predictor of health outcomes, and validated measures of adherence are necessary at all stages of therapy from drug development to prescription. Many of the existing metrics of drug adherence (e.g.

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Laser desorption followed by post electrospray ionization requires synchronized timing of the key events (sample desorption/ionization, mass spectrometry analysis, and sample translation) necessary to conduct mass spectrometry imaging (MSI) with adequate analyte sensitivity. In infrared matrix-assisted laser desorption electrospray ionization (IR-MALDESI) MSI analyses, two laser pulses are used for analysis at each volumetric element, or voxel, of a biological sample and ion accumulation in the C-trap exceeding 100 ms is necessary to capture all sample-associated ions using an infrared laser with a 20 Hz repetition rate. When coupled to an Orbitrap-based mass spectrometer like the Q Exactive Plus, this time window for ion accumulation exceeds dynamically controlled trapping of samples with comparable ion flux by Automatic Gain Control (AGC), which cannot be used during MSI analysis.

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Analyte signal in a laser desorption/postionization scheme such as infrared matrix-assisted laser desorption electrospray ionization (IR-MALDESI) is strongly coupled to the degree of overlap between the desorbed plume of neutral material from a sample and an orthogonal electrospray. In this work, we systematically examine the effect of desorption conditions on IR-MALDESI response to pharmaceutical drugs and endogenous lipids in biological tissue using a design of experiments approach. Optimized desorption conditions have then been used to conduct an untargeted lipidomic analysis of whole body sagittal sections of neonate mouse.

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Persistent HIV replication within active viral reservoirs may be caused by inadequate antiretroviral penetration. Here, we used mass spectrometry imaging with infrared matrix-assisted laser desorption-electrospray ionization to quantify the distribution of efavirenz within tissues from a macaque dosed orally to a steady state. Intratissue efavirenz distribution was heterogeneous, with the drug concentrating in the lamina propria of the colon, the primary follicles of lymph nodes, and the brain gray matter.

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A quantitative mass spectrometry imaging (QMSI) technique using infrared matrix-assisted laser desorption electrospray ionization (IR-MALDESI) is demonstrated for the antiretroviral (ARV) drug emtricitabine in incubated human cervical tissue. Method development of the QMSI technique leads to a gain in sensitivity and removal of interferences for several ARV drugs. Analyte response was significantly improved by a detailed evaluation of several cationization agents.

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This work describes the coupling of the IR-MALDESI imaging source with the Q Exactive mass spectrometer. IR-MALDESI MSI was used to elucidate the spatial distribution of several HIV drugs in cervical tissues that had been incubated in either a low or high concentration. Serial sections of those analyzed by IR-MALDESI MSI were homogenized and analyzed by LC-MS/MS to quantify the amount of each drug present in the tissue.

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