Nari Talaty

Direct, trace level detection of explosives on ambient surfaces by desorption electrospray ionization mass spectrometry

Desorption electrospray ionization (DESI) mass spectrometry is used to detect trace amounts of explosives present on a variety of ambient surfaces in 5-second analysis times without any sample preparation.

Rapid in situ detection of alkaloids in plant tissue under ambient conditions using desorption electrospray ionization

Desorption electrospray ionization (DESI) mass spectrometry is applied to the in situ detection of alkaloids in the tissue of poison hemlock (Conium maculatum), jimsonweed (Datura stramonium) and deadly nightshade (Atropa belladonna). The experiment is carried out by electrospraying micro-droplets of solvent onto native or freshly-cut plant tissue surfaces. No sample preparation is required and the mass spectra are recorded under ambient conditions, in times of a few seconds. The impact of the sprayed droplets on the surface produces gaseous ions from organic compounds originally present in the plant tissue. The effects of operating parameters, including the electrospray high voltage, heated capillary temperature, the solvent infusion rate and the carrier gas pressure on analytical performance are evaluated and optimized. Different types of plant material are analyzed including seeds, stems, leaves, roots and flowers. All the previously reported alkaloids have been detected in C. maculatum, while fifteen out of nineteen known alkaloids for D. stramonium and the principal alkaloids of A. belladonna were also identified. All identifications were confirmed by tandem mass spectrometry. Results obtained show similar mass spectra, number of alkaloids, and signal intensities to those obtained when extraction and separation processes are performed prior to mass spectrometric analysis. Evidence is provided that DESI ionization occurs by both a gas-phase ionization process and by a droplet pick-up mechanism. Quantitative precision of DESI is compared with conventional electrospray ionization mass spectrometry (after sample workup) and the RSD values for the same set of 25 dicotyledonous C. maculatum seeds (one half of each seed analyzed by ESI and the other by DESI) are 9.8% and 5.2%, respectively.

Rapid analysis of metabolites and drugs of abuse from urine samples by desorption electrospray ionization-mass spectrometry

Urine samples obtained from drug abusers were screened for drugs of abuse and their metabolites using DESI-MS and the results obtained were compared to results obtained from GC-MS experiments. The detected analyte classes included amphetamines, opiates, cannabinoids and benzodiazepines. The compounds detected were codeine, morphine, oxymorphone, 11-nor-9-carboxy-Delta(9)-tetrahydrocannabinol, Delta(9)-tetrahydrocannabinol, alprazolam, temazepam, oxazepam, N-desmethyldiazepam (nordiazepam) and hydroxytemazepam. Identities of all the analytes were confirmed by tandem mass spectrometry, matching MS/MS spectra with authentic standard compounds. The concentrations of the analytes in the samples were obtained from semi-quantitative GC-MS studies and were in the range of 270-22,000 ng mL(-1). The analytes could be detected by DESI even after a hundred-fold dilution indicating that the sensitivity of DESI was more than adequate for this study. Selectivity in the DESI-MS measurements for different kinds of analytes could be increased further by optimizing the spray solvent composition: the use of an entirely aqueous solvent enhanced the signal of polar analytes, such as the benzodiazepines, whereas the use of a spray solvent with a high organic content increased the signal of less polar analytes, such as codeine and morphine.

Rapid ambient mass spectrometric profiling of intact, untreated bacteria using desorption electrospray ionization

Desorption electrospray ionization (DESI) allows the rapid acquisition of highly reproducible mass spectra from intact microorganisms under ambient conditions; application of principal component analysis to the data allows sub-species differentiation.

A quantitation method for mass spectrometry imaging

A new quantitation method for mass spectrometry imaging (MSI) with matrix-assisted laser desorption/ionization (MALDI) has been developed. In this method, drug concentrations were determined by tissue homogenization of five 10 µm tissue sections adjacent to those analyzed by MSI. Drug levels in tissue extracts were measured by liquid chromatography coupled to tandem mass spectrometry (LC/MS/MS). The integrated MSI response was correlated to the LC/MS/MS drug concentrations to determine the amount of drug detected per MSI ion count. The study reported here evaluates olanzapine in liver tissue. Tissue samples containing a range of concentrations were created from liver harvested from rats administered a single dose of olanzapine at 0, 1, 4, 8, 16, 30, or 100 mg/kg. The liver samples were then analyzed by MALDI-MSI and LC/MS/MS. The MALDI-MSI and LC/MS/MS correlation was determined for tissue concentrations of ~300 to 60,000 ng/g and yielded a linear relationship over two orders of magnitude (R(2) = 0.9792). From this correlation, a conversion factor of 6.3 ± 0.23 fg/ion count was used to quantitate MSI responses at the pixel level (100 µm). The details of the method, its importance in pharmaceutical analysis, and the considerations necessary when implementing it are presented.

Targeted metabolomic analysis of Escherichia coli by desorption electrospray ionization and extractive electrospray ionization mass spectrometry

Desorption electrospray ionization (DESI) was utilized to monitor the presence of targeted central carbon metabolites within bacterial cell extracts and the quench supernatant of Escherichia coli. The targeted metabolites were identified through tandem mass spectrometry (MS/MS) product ion scans using collision-induced dissociation in the negative ion mode. Picogram detection limits were achieved for a majority of the metabolites during MS/MS analysis of standard metabolite solutions. In a [U-(13)C]glucose pulse experiment, where uniformly labeled glucose was fed to E. coli, the corresponding fragment ions from labeled metabolites in extracts were generally observed. There was evidence of matrix effects including moderate suppression by other metabolites within the spectra of the labeled and unlabeled extracts. To improve the specificity and sensitivity of detection, optimized in situ ambient chemical reactions using DESI and extractive electrospray ionization (EESI) were carried out for targeted compounds. This study provides the first indication of the potential to perform in situ targeted metabolomics of a bacterial sample via ambient ionization mass spectrometry.

Desorption electrospray ionization with a portable mass spectrometer: in situ analysis of ambient surfaces

Desorption electrospray ionization (DESI) is implemented on a portable mass spectrometer and used to demonstrate in situ detection of active ingredients in pharmaceutical preparations, alkaloids in plant tissues, explosives, chemical warfare agent simulants and agricultural chemicals from a variety of surfaces; air monitoring applications using DESI are also introduced.

Current status and future prospects for enabling chemistry technology in the drug discovery process

This review covers recent advances in the implementation of enabling chemistry technologies into the drug discovery process. Areas covered include parallel synthesis chemistry, high-throughput experimentation, automated synthesis and purification methods, flow chemistry methodology including photochemistry, electrochemistry, and the handling of “dangerous” reagents. Also featured are advances in the “computer-assisted drug design” area and the expanding application of novel mass spectrometry-based techniques to a wide range of drug discovery activities.

Accelerated multi-reagent copper catalysed coupling reactions in micro droplets and thin films

Electrospray (ES) and paper spray (PS) mass spectrometry were used to create confined liquid volumes in which accelerated air and water sensitive, heterogeneous, copper catalysed C–O and C–N coupling reactions occur. Significant reaction acceleration was observed compared to the bulk reaction which required elevated temperatures and time for completion. Macroscopic amounts of product (mg scale) were prepared using offline ES within minutes. The trends in reactivity observed for several reagents matched those of the bulk reactions making droplet accelerated reactions good mimics of the bulk chemistry.

From Discovery to Finished Products: Innovative Applications of Surface Mass Spectrometry in Pharmaceutical Industry

Surface mass spectrometry allows the direct analysis of the surface composition of materials or biological tissues, which eliminates sample processing, minimizes solvent consumption, and can increase efficiency by 5-10 times compared to standard LC-MS methods. Two mass spectrometry ionization methods, desorption electrospray ionization (DESI) and matrix assisted laser desorption ionization (MALDI) applied to surface analysis and imaging will be presented.