Rapid analysis of fentanyls and other novel psychoactive substances in substance use disorder patient urine using paper spray mass spectrometry.

Rationale: Drug overdose deaths due to fentanyls and other novel psychoactive substances (NPS) are on the rise. The higher potencies of fentanyl analogs compared with morphine require new technologies to identify and quantitate NPS.

Methods: Paper spray tandem mass spectrometry (MS/MS) and high-resolution mass spectrometry were used to identify and measure fentanyl analogs as well as common drugs of abuse in urine samples from substance use disorder clinics.

Limited Azithromycin Localization to Rabbit Meibomian Glands Revealed by LC-MS-Based Bioanalysis and DESI Imaging.

Meibomian gland dysfunction (MGD) is the leading cause of dry eye, and although it affects approximately 4% of the population, treatment options remain limited. Topical azithromycin is one of the most promising pharmacological agents because of its multiple mechanisms of action and long sustainability. Azithromycin is frequently used as an off-label medication in the U.

Rapid screening and identification of novel psychoactive substances using PaperSpray interfaced to high resolution mass spectrometry.

The simple and rapid detection and identification of designer drugs is of substantial importance to forensic scientists and law enforcement. Although synthetic cathinones, cannabinoids, and other common novel psychoactive substances (NPS) are produced for purposes that do not include human consumption, they are regularly abused. The analysis of these compounds is often achieved using mass spectrometry, but can be complicated by the lack of spectral libraries and the scarcity of simple and reliable sample introduction techniques.

Mass spectrometry imaging of levofloxacin distribution in TB-infected pulmonary lesions by MALDI-MSI and continuous liquid microjunction surface sampling.

A multi-modal mass spectrometry imaging (MSI) and profiling approach has been applied to assess the partitioning of the anti-TB fluoroquinolone levofloxacin into pulmonary lesions. Matrix-assisted laser desorption ionization mass spectrometry imaging (MALDI-MSI) and a commercial liquid microjunction surface sampling technology (LMJ-SSP), or flowprobe, have been used to both spatially profile and image drug distributions in lung tissue sections from TB-infected rabbits following oral administration of a single human-equivalent dose. Levofloxacin levels were highest at 6 h post-dose in normal lung, cellular granuloma, and necrotic caseum compartments.

Analysis of dried blood spots using DESI mass spectrometry.

Dried blood spot (DBS) analysis using mass spectrometry is an invaluable technique for examining blood markers of inborn metabolic diseases in clinical laboratories. Implementation of DBS sampling and analysis in pharmaceutical development have more recently gained traction due to the advantages of convenience in sample procurement and logistics, as well as the innate advantages associated with the collection of lower blood volumes. While there are several realized advantages of DBS, the bioanalytical laboratory is disadvantaged and burdened with additional preparative steps prior to analysis.

Data processing for 3D mass spectrometry imaging.

Data processing for three dimensional mass spectrometry (3D-MS) imaging was investigated, starting with a consideration of the challenges in its practical implementation using a series of sections of a tissue volume. The technical issues related to data reduction, 2D imaging data alignment, 3D visualization, and statistical data analysis were identified. Software solutions for these tasks were developed using functions in MATLAB.

Development of stereotactic mass spectrometry for brain tumor surgery.

Background: Surgery remains the first and most important treatment modality for the majority of solid tumors. Across a range of brain tumor types and grades, postoperative residual tumor has a great impact on prognosis. The principal challenge and objective of neurosurgical intervention is therefore to maximize tumor resection while minimizing the potential for neurological deficit by preserving critical tissue.

Elution, partial separation, and identification of lipids directly from tissue slices on planar chromatography media by desorption electrospray ionization mass spectrometry.

A method for the examination of intact tissue sections for gangliosides and other lipids using desorption electrospray ionization (DESI) mass spectrometry (MS) is presented. In the present work, thin tissue slices (16 μm) taken from the rat brain are thaw mounted onto planar chromatographic media and the lipids are eluted, partially separated, and analyzed directly from the plate by DESI-MS in the negative ion mode. With the lanes scanned parallel to the direction of the chromatographic separation in the full scan mode, the selected ion current associated with ions of separated lipid molecules is plotted in order of increasing Rf values.

Coupling desorption electrospray ionization with solid-phase microextraction for screening and quantitative analysis of drugs in urine.

Direct analysis of silica C(18)-coated solid-phase microextraction (SPME) fibers using desorption electrospray ionization mass spectrometry (DESI-MS) for the purpose of analyzing drugs from raw urine is presented. The method combines a simple, inexpensive, and solvent-less sample preparation technique with the specificity and speed of DESI-MS and MS/MS. Extraction of seven drugs from raw urine is performed using specially designed SPME fibers coated uniformly with silica-C(18) stationary phase.

Desorption electrospray ionization-mass spectrometry for the detection of analytes extracted by thin-film molecularly imprinted polymers.

Desorption electrospray ionization-mass spectrometry (DESI-MS) is a powerful technique for the analysis of solid and liquid surfaces that has found numerous applications in the few years since its invention. For the first time, it is applied to the detection of analytes extracted by molecularly imprinted polymers (MIPs) in a thin-film format. MIPs formed with 2,4-dichlorophenoxyacetic acid (2,4-D) as the template were used for the extraction of this analyte from aqueous solutions spiked at concentrations of 0.

Direct analysis of Salvia divinorum leaves for salvinorin A by thin layer chromatography and desorption electrospray ionization multi-stage tandem mass spectrometry.

Salvia divinorum is widely cultivated in the US, Mexico, Central and South America and Europe and is consumed for its ability to produce hallucinogenic effects similar to those of other scheduled hallucinogenic drugs, such as LSD. Salvinorin A (SA), a kappa opiod receptor agonist and psychoactive constituent, is found primarily in the leaves and to a lesser extent in the stems of the plant. Herein, the analysis of intact S.

Direct analysis of dried blood spots utilizing desorption electrospray ionization (DESI) mass spectrometry.

A novel approach to the quantitative determination of xenobiotics in whole blood samples without sample preparation or chromatography is described. This method is based on direct analysis of microlitre volumes of blood which are spotted onto specialized paper cards and dried, with the resulting dried blood spots (DBS) analyzed directly via desorption electrospray ionization (DESI) mass spectrometry (MS). Using sitamaquine, terfenadine, and prazosin as model compounds with verapamil as a common internal standard, this methodology demonstrated detection of each compound down to 10 ng mL(-1) from DBS where standard calibration curves show linearity from 10-10,000 ng mL(-1) with r(2) > 0.

Evaluation and performance of desorption electrospray ionization using a triple quadrupole mass spectrometer for quantitation of pharmaceuticals in plasma.

The present work describes the methodology and investigates the performance of desorption electrospray ionization (DESI) combined with a triple quadrupole mass spectrometer for the quantitation of small drug molecules in human plasma. Amoxepine, atenolol, carbamazepine, clozapine, prazosin, propranolol and verapamil were selected as target analytes while terfenadine was selected as the internal standard common to each of the analytes. Protein precipitation of human plasma using acetonitrile was utilized for all samples.

Desorption electrospray ionization mass spectrometry: Imaging drugs and metabolites in tissues.

Ambient ionization methods for MS enable direct, high-throughput measurements of samples in the open air. Here, we report on one such method, desorption electrospray ionization (DESI), which is coupled to a linear ion trap mass spectrometer and used to record the spatial intensity distribution of a drug directly from histological sections of brain, lung, kidney, and testis without prior chemical treatment. DESI imaging provided identification and distribution of clozapine after an oral dose of 50 mg/kg by: i) measuring the abundance of the intact ion at m/z 327.

Ambient molecular imaging by desorption electrospray ionization mass spectrometry.

Desorption electrospray ionization (DESI) allows the direct analysis of ordinary objects or pre-processed samples under ambient conditions. Among other applications, DESI is used to identify and record spatial distributions of lipids and drug molecules in biological tissue sections. This technique does not require sample preparation other than production of microtome tissue slices and does not involve the use of ionization matrices.

Desorption electrospray ionization (DESI) mass spectrometry and tandem mass spectrometry (MS/MS) of phospholipids and sphingolipids: ionization, adduct formation, and fragmentation.

Desorption electrospray ionization (DESI) mass spectrometry was evaluated for the characterization of glycerophospholipid standards, including glycerophosphocholine (GPCho), glycerophosphoglycerol (GPGro), glycerophosphoethanolamine (GPEtn), glycerophosphoserine (GPSer), glycerophosphoinositol (GPIns), cardiolipin (CL), and sphingolipid standards, including sulfatides (ST) and sphingomyelin (SM). Of specific interest were the effects of surface and solvent composition on signal stability and intensity, along with the ions observed in the full scan mode and the fragmentations seen upon collisional activation for each of the above classes. These experiments were performed without the addition of matrix compounds to the sample and were conducted in the free ambient environment at atmospheric pressure.

Desorption Electrospray Ionization: Proteomics Studies by a Method That Bridges ESI and MALDI.

INTRODUCTIONDesorption electrospray ionization (DESI) is a desorption ionization (DI) method by nature, and, like matrix-assisted laser desorption/ionization (MALDI), it is used for the analysis of material present on a surface. DESI includes features reminiscent of electrospray ionization (ESI) in respect to both its instrumental and mechanistic aspects. However, the analyte in the DESI experiment is not in solution as in ESI.

In Situ Desorption Electrospray Ionization (DESI) Analysis of Tissue Sections.

INTRODUCTIONDesorption electrospray ionization (DESI) allows in situ analysis of biological tissues. The analysis of less abundant protein constituents within a tissue sample often requires the removal of lipid species prior to analysis, similar to the situation with matrix-assisted laser desorption/ionization (MALDI). After removal of lipid constituents, the tissue can be treated with protease to degrade proteins present in the tissue.

Desorption Electrospray Ionization (DESI) Analysis of Tryptic Digests/Peptides.

INTRODUCTIONThe analytical utility of desorption electrospray ionization (DESI) is such that it can be applied to qualitative proteomics research in the same way as matrix-assisted laser desorption/ionization (MALDI) and electrospray ionization (ESI) methods, although little work has yet been reported in this regard. Because DESI is a surface analysis technique and easily automated, it can be implemented for high-throughput applications, which include the analysis of chromatographic fractions of digested proteins. The analysis of tryptic peptides follows the same protocols as in typical MALDI or ESI methods, except that the mixture is spotted directly onto an insulating surface, allowed to dry, and analyzed directly without adding matrix compounds (as in the case of MALDI methods).

Desorption Electrospray Ionization (DESI) Analysis of Intact Proteins/Oligopeptides.

INTRODUCTIONDesorption electrospray ionization (DESI) is amenable to the study of intact proteins in complex mixtures, including blood or other biological media. Intact proteins can be desorbed and ionized from the surface under gentle (soft) conditions to produce compact conformations of the protein. A procedure for DESI analysis of intact proteins and oligopeptides using mass spectrometry (MS) is described here.

Detection Technologies. Ambient mass spectrometry.

A recent innovation in mass spectrometry is the ability to record mass spectra on ordinary samples, in their native environment, without sample preparation or preseparation by creating ions outside the instrument. In desorption electrospray ionization (DESI), the principal method described here, electrically charged droplets are directed at the ambient object of interest; they release ions from the surface, which are then vacuumed through the air into a conventional mass spectrometer. Extremely rapid analysis is coupled with high sensitivity and high chemical specificity.

Coupling desorption electrospray ionization with ion mobility/mass spectrometry for analysis of protein structure: evidence for desorption of folded and denatured States.

A desorption electrospray ionization (DESI) source has been coupled to an ion mobility time-of-flight mass spectrometer for the analysis of proteins. Analysis of solid-phase horse heart cytochrome c and chicken egg white lysozyme proteins with different DESI solvents and conditions shows similar mass spectra and charge state distributions to those formed when using electrospray to analyze these proteins in solution. The ion mobility data show evidence for compact ion structures [when the surface is exposed to a spray that favors retention of "nativelike" structures (50:50 water:methanol)] or elongated structures [when the surface is exposed to a spray that favors "denatured" structures (49:49:2 water:methanol:acetic acid)].

Desorption electrospray ionization mass spectrometry for the analysis of pharmaceuticals and metabolites.

The performance of desorption electrospray ionization (DESI) in the analysis of a group of pharmaceuticals and their glucuronic acid conjugates is reported. The suitability of different sprayer solvents and different surfaces was examined. In the positive ion mode, water/methanol/trifluoroacetic acid performed best, whereas, in the negative ion mode, water/methanol/ammonium hydroxide was found to be the most suitable spray solvent.