Robert B. Cody

Atmospheric pressure ion source

This review of atmospheric pressure ion sources discusses major developments that have occurred since 1991. Advances in the instrumentation and understanding of the key physical principles are the primary focus. Developments with electrospray and atmospheric pressure chemical ionization and variations encompassing adaptations for surface analysis, ambient air analysis, high throughput, and modification of the ionization mechanism are covered. An important and limiting consequence of atmospheric pressure chemical ionization, chemical noise, is discussed as is techniques being employed to ameliorate the problem. Ion transfer and transport from atmospheric pressure into deep vacuum is an area undergoing constant improvement and refinement so is given considerable consideration in this review.

Characterization of Solid Counterfeit Drug Samples by Desorption Electrospray Ionization and Direct- analysis-in-real-time Coupled to Time-of-flight Mass Spectrometry

The search for more versatile, sensitive, and robust ionization methods is a recurring theme in mass spectrometry (MS). Since the discovery of electrospray ionization (ESI) and matrix-assisted laser desorption/ionization (MALDI), many developments such as atmospheric pressure MALDI, nanospray ionization, Venturi-assisted electrospray, and ion-funnel atmospheric pressure interfaces, have paved the way to improved characterization of small molecules and biomolecules. One of the bottlenecks in achieving high sample throughput with both ESI and MALDI is the need to dissolve, extract, and/or filter the sample prior to analysis. Moreover, vacuum-incompatible materials cannot be easily investigated by MS without disturbing their innate structure. Recently, two novel methods for the direct ionization of solid samples under atmospheric pressure by MS were reported: desorption electrospray ionization (DESI) and direct analysis in real time (DART). More recently, McEwen et al. described a modified atmospheric pressure chemical ionization (APCI) technique for the direct analysis of solids which they named atmospheric pressure solids analysis probe (ASAP). DESI makes use of a high-speed liquid spray directed at a sample held or deposited on a surface at atmospheric pressure. Ions generated during this process are sampled by a mass spectrometer. Several DESI applications such as the mapping of analytes separated by thin-layer chromatography, the detection of explosives, and the screening of pharmaceutical tablets and illicit drugs quickly followed the proof-of-principle description of the method. DART involves an ionizing beam of metastable He atoms (S1, 19.8 eV) generated by a corona discharge. The DART ionization mechanism is still not completely understood. In negative ion mode, the metastable He atoms generate electrons that produce negatively charged oxygen–water clusters, which then form the corresponding adducts. In positive ion mode, metastable He atoms generate protonated gaseous water clusters by Penning ionization. Then, by proton exchange, these clusters form [M+H] ions, which are generally the predominant species. DART’s high throughput coupled with the high mass accuracy now attainable with modern time-of-flight mass (TOF) analyzers and accurate isotopic abundance measurements make it especially suitable for the rapid identification of unknown species in solid materials. One particularly relevant example is counterfeit drug samples. Counterfeit drugs are defined as those that are “deliberately and fraudulently mislabeled with respect to identity and/or source”. They may include products with the “wrong” ingredient(s), without active ingredient(s), or with an insufficient amount of active ingredient(s). In recent years, a particularly alarming case of drug counterfeiting has been reported by field researchers who have detected counterfeit products that mimic the vital antimalarial, artesunate. The consumption of fake antimalarials has resulted in the death of many patients. Evidence suggests that the production of counterfeit artesunate tablets is on an industrial scale. For example, one health care organization in southeast Asia unwittingly purchased 100,000 artesunate tablets which were later shown to be counterfeit. Classic hyphenated analysis methods, such as liquid chromatography–mass spectrometry (LC–MS), lack the required sample throughput to survey such large numbers of samples in a reasonable amount of time. Figure 1a shows a schematic of the DART TOF MS setup used to screen 52 representative samples of a database containing more than 400 artesunate-based antimalarial tablets. Figure 1b and 1c show the negative ion mode DART TOF MS data of genuine and counterfeit artesunate (M) tablets, respectively. The spectrum shown in Figure 1b has signals corresponding to the diagnostic [M H] artesunate anion (experimental m/z=383.1702, calculated m/z=383.1711) and palmitic acid, a ubiquitous contaminant. Artesunate fragment ions due to dissociation of the highly labile artesunate carboxylic acid side [a] Prof. Dr. F. M. Fern ndez, C. Y. Hampton School of Chemistry and Biochemistry Georgia Institute of Technology 770 State St. Atlanta, GA 30332 (USA) Fax: (+1)404-385-6447 E-mail : facundo.fernandez@chemistry.gatech.edu [b] Dr. R. B. Cody JEOL USA, Inc. 11 Dearborn Road, Peabody, MA 01960 (USA) [c] Dr. M. D. Green Division of Parasitic Diseases, National Center for Infectious Diseases Center for Disease Control and Prevention 1600 Clifton Road, Mailstop F12, Atlanta, GA 30333 (USA) [d] Dr. R. McGready Shoklo Malaria Research Unit Mae Sot Tak (Thailand) [e] Dr. S. Sengaloundeth Food and Drug Department Ministry of Health, Government of the Lao PDR Vientiane (Lao PDR) [f] Prof. N. J. White, Dr. P. N. Newton Microbiology Laboratory, Mahosot Hospital Wellcome Trust–Mahosot Hospital–Oxford Tropical Medicine Research Collaboration, Vientiane (Lao PDR) and Centre for Clinical Vaccinology and Tropical Medicine Churchill Hospital, Oxford University, Oxford, OX37LJ (UK) [] Prof. White is also affiliated with: Wellcome Trust–Mahidol University–Oxford Tropical Medicine Research Programme, Faculty of Tropical Medicine Mahidol University, Bangkok, 10400 (Thailand)

Differentiating Writing Inks Using Direct Analysis in Real Time Mass Spectrometry

ABSTRACT: Writing ink analysis is used in establishing document authenticity and the sources and relative ages of written entries. Most analytical methods require removing samples or visibly altering the document. Nondestructive, in situ analysis of writing inks on paper without visible alteration is possible using mass spectrometry with a new ion source called Direct Analysis in Real Time. Forty‐three different black and blue ballpoint, black fluid, and black gel inks were examined. Both dyes and persistent but thermally labile components of the inks contribute to the mass spectra, principally as protonated molecules [M+H]+. Numerous ink components were identified from the spectra. The spectra were placed in a searchable library, which was then challenged with two spectra from each of the 43 inks. The best match for each of the challenge spectra was correct for all but one ink, which matched with a very similar ink by the same manufacturer.

Laser ionization source for ion cyclotron resonance spectroscopy. Application to atomic metal ion chemistry

Abstract A pulsed nitrogen laser with a pulse energy of 5 mJ released in 5 ns (power density ca. 107W cm−2) has been used in conjunction with an ion cyclotron resonance spectrometer to generate a variety of atomic metal ions including Cu+ and Ag+ from their respective metals and Cr+, Fe+, and Ni+ from a stainless steel sample. A brief study of the chemistry of Cu+ and Ag+ is presented. These results indicate the potential of the combined laser ionization—ion cyclotron resonance technique for studying solid samples and the chemistry of ions difficult to generate by conventional methods.

Ambient generation of fatty acid methyl ester ions from bacterial whole cells by direct analysis in real time (DART) mass spectrometry

Direct analysis in real time (DART) is implemented on a time-of-flight (TOF) mass spectrometer, and used for the generation of fatty acid methyl esters (FAMEs) ions from whole bacterial cells.

Developments in analytical fourier-transform mass spectrometry

Abstract Development of a differentially-pumped, dual-cell geometry, coupled with the evolution of pulsed-laser desorption and Cs + -secondary-ion mass spectrometric (s.i.m.s.) desorption methods, has improved the analytical utility of Fourier-transform mass spectrometry (F.t.m.s.). A survey of applications and performances obtained in our laboratories is presented. Among the topics covered are ultra-high-resolution electron-impact and chemical-ionization mass spectra, gas chromatography/F.t.m.s. performance, pulsed Cs + -s.i.m.s./F.t.m.s. with cooled liquid matrices and solid samples, laser desorption/F.t.m.s. and accurate mass measurements taken under each of these modes of operation.

Cuticular hydrocarbon analysis of an awake behaving fly using direct analysis in real-time time-of-flight mass spectrometry

In mammals and insects, pheromones strongly influence social behaviors such as aggression and mate recognition. In Drosophila melanogaster, pheromones in the form of cuticular hydrocarbons play prominent roles in courtship. GC/MS is the primary analytical tool currently used to study Drosophila cuticular hydrocarbons. Although GC/MS is highly reproducible and sensitive, it requires that the fly be placed in a lethal solution of organic solvent, thereby impeding further behavioral studies. We present a technique for the analysis of hydrocarbons and other surface molecules from live animals by using direct analysis in real-time (DART) MS. Cuticular hydrocarbons were sampled from the surface of a restrained, awake behaving fly by using several brief, carefully controlled depressions of the abdomen with a small steel probe. DART mass spectral analysis of the probe detected ions with mass-to-charge ratio (m/z) of the protonated molecule corresponding to many of the previously identified unsaturated hydrocarbons. Six additional cuticular hydrocarbons also were identified. Consistent with previous GC/MS studies, male and female differences in chemical composition were evident. Spatial differences in the expression profile also were observed on males. Sampling from an individual female first as a virgin and then 45 and 90 min after successful copulation showed that mass signals likely to correspond to cis-vaccenyl acetate, tricosene, and pentacosene increased in relative intensity after courtship. This method provides near-instantaneous analysis of an individual animals chemical profile in parallel with behavioral studies and could be extended to other models of pheromone-mediated behavior.

Selective ionization of melamine in powdered milk by using argon direct analysis in real time (DART) mass spectrometry.

5-Hydroxymethylfurfural (5-HMF) is a compound with the elemental composition C(6)H(6)O(3) that is present in powdered milk. Protonated 5-HMF (calculated m/z 127.0395) has the same nominal m/z as protonated melamine (calculated m/z 127.0732) and can interfere with direct analysis of melamine in powdered milk. Tandem mass spectrometry and high-resolution mass spectrometry have been previously used to distinguish melamine from 5-HMF. An alternative approach is presented here that uses the direct analysis in real time (DART) ion source operated with argon gas in combination with acetylacetone and pyridine reagent gases to selectively ionize melamine and eliminate the interference from 5-HMF. High-resolution/accurate mass data were used to verify the elimination of the 5-HMF interference and confirm the melamine elemental composition. With further refinement, this technique could lead to a rapid analysis method for screening large numbers of samples.

Temperature-dependent release of volatile organic compounds of eucalypts by direct analysis in real time (DART) mass spectrometry

A method is described for the rapid identification of biogenic, volatile organic compounds (VOCs) emitted by plants, including the analysis of the temperature dependence of those emissions. Direct analysis in real time (DART) enabled ionization of VOCs from stem and leaf of several eucalyptus species including E. cinerea, E. citriodora, E. nicholii and E. sideroxylon. Plant tissues were placed directly in the gap between the DART ionization source skimmer and the capillary inlet of the time-of-flight (TOF) mass spectrometer. Temperature-dependent emission of VOCs was achieved by adjusting the temperature of the helium gas into the DART ionization source at 50, 100, 200 and 300 degrees C, which enabled direct evaporation of compounds, up to the onset of pyrolysis of plant fibres (i.e. cellulose and lignin). Accurate mass measurements facilitated by TOF mass spectrometry provided elemental compositions for the VOCs. A wide range of compounds was detected from simple organic compounds (i.e. methanol and acetone) to a series of monoterpenes (i.e. pinene, camphene, cymene, eucalyptol) common to many plant species, as well as several less abundant sesquiterpenes and flavonoids (i.e. naringenin, spathulenol, eucalyptin) with antioxidant and antimicrobial properties. The leaf and stem tissues for all four eucalypt species showed similar compounds. The relative abundances of methanol and ethanol were greater in stem wood than in leaf tissue suggesting that DART could be used to investigate the tissue-specific transport and emissions of VOCs.

Applications of direct analysis in real time-mass spectrometry (DART-MS) in Allium chemistry. (Z)-butanethial S-oxide and 1-butenyl thiosulfinates and their S-(E)-1-butenylcysteine S-oxide precursor from Allium siculum.

Lachrymatory (Z)-butanethial S-oxide along with several 1-butenyl thiosulfinates was detected by DART mass spectrometry upon cutting Allium siculum , a popular ornamental Allium species used in some cultures as a spice. (Z)-Butanethial S-oxide isolated from the plant was shown to be identical to a synthetic sample. Its likely precursor, (R(S),R(C),E)-S-(1-butenyl)cysteine S-oxide (homoisoalliin), was isolated from homogenates of A. siculum, and a closely related species Allium tripedale , and fully characterized. Through use of LC-MS, a series of related gamma-glutamyl derivatives were tentatively identified in A. siculum and A. tripedale homogenates, including gamma-glutamyl-(E)-S-(1-butenyl)cysteine and its S-oxide, gamma-glutamyl-S-butylcysteine and its S-oxide, and gamma-glutamyl-S-methylcysteine and its S-oxide. Because compounds containing the 1-butenyl group have not been previously identified in genus Allium species, this work extends the range of known Allium sulfur compounds. The general applicability of DART mass spectrometry in identifying naturally occurring, thermally fragile thial S-oxides and thiosulfinates is illustrated with onion, Allium cepa , as well as a plant from a different genus, Petiveria alliacea .