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Journal of the American Society for Mass Spectrometry | Year: 2015

Mass selective axial ejection (MSAE) from a low pressure linear ion trap (LIT) is investigated in the presence of added auxiliary nonlinear radio frequency (rf) fields. Nonlinear rf fields allow ions to be ejected with high sensitivity at large excitation amplitudes and reduced deleterious effects of space charge. These permit the operation of the LIT at ion populations considerably larger than the space charge limit usually observed in the absence of the nonlinear fields while maintaining good spectral resolution and mass accuracy. Experimental data show that the greater the strength of the nonlinear field, the less the effects of space charge on mass assignment and peak width. The only deleterious effect is a slight broadening of the mass spectral peaks at the highest values of added nonlinear fields used. © 2015 American Society for Mass Spectrometry.

Baba T.,Sciex | Campbell J.L.,Sciex
Journal of the American Society for Mass Spectrometry | Year: 2015

We report on the formation and "capture" of polyradical protein cations after an electron capture event. Performed in a unique electron-capture dissociation (ECD) instrument, these experiments can generate reduced forms of multiply protonated proteins by sequential charge reduction using electrons with ~1 eV. The true structures of these possible polyradicals is considered: Do the introduced unpaired electrons recombine quickly to form a new two-electron bond, or do these unpaired electrons exist as radical sites with appropriate chemical reactivity? Using an established chemical probe - radical quenching with molecular oxygen - we demonstrate that these charge-reduced protein cations are indeed polyradicals that form adducts with up to three molecules of oxygen (i.e.; tri-radical protein cations) that are stable for at least 100 ms. © 2015 American Society for Mass Spectrometry.

Diao X.,U.S. National Institute on Drug Abuse | Wohlfarth A.,U.S. National Institute on Drug Abuse | Pang S.,SCIEX | Scheidweiler K.B.,U.S. National Institute on Drug Abuse | Huestis M.A.,U.S. National Institute on Drug Abuse
Clinical Chemistry | Year: 2016

BACKGROUND: Despite increasing prevalence of novel psychoactive substances, no human metabolism data are currently available, complicating laboratory documentation of intake in urine samples and assessment of the drugs' pharmacodynamic, pharmacokinetic, and toxicological properties. In 2014, THJ-018 and THJ-2201, synthetic cannabinoid indazole analogs of JWH-018 and AM-2201, were identified, with the National Forensic Laboratory Information System containing 220 THJ-2201 reports. Because of numerous adverse events, the Drug Enforcement Administration listed THJ-2201 as Schedule I in January 2015. METHODS: We used high-resolution mass spectrometry (HR-MS) (TripleTOF 5600+) to identify optimal metabolite markers after incubating 10 μmol/L THJ-018 and THJ-2201 in human hepatocytes for 3 h. Data were acquired via full scan and information-dependent acquisition triggered product ion scans with mass defect filter. In silico metabolite predictions were performed with MetaSite and compared with metabolites identified in human hepatocytes. RESULTS: Thirteen THJ-018 metabolites were detected, with the major metabolic pathways being hydroxylation on the N-pentyl chain and further oxidation or glucuronidation. For THJ-2201, 27 metabolites were observed, predominantly oxidative defluorination plus subsequent carboxylation or glucuronidation, and glucuronidation of hydroxylated metabolites. Dihydrodiol formation on the naphthalene moiety was observed for both compounds. MetaSite prediction matched well with THJ-018 hepatocyte metabolites but underestimated THJ-2201 oxidative defluorination. CONCLUSIONS: With HR-MS for data acquisition and processing, we characterized THJ-018 and THJ-2201 metabolism in human hepatocytes and suggest appropriate markers for laboratories to identify THJ-018 and THJ-2201 intake and link observed adverse events to these new synthetic cannabinoids. © 2015 American Association for Clinical Chemistry.

Although lipids are critical components of many cellular assemblies and biological pathways, accurate descriptions of their molecular structures remain difficult to obtain. Many benchtop characterization methods require arduous and time-consuming procedures, and multiple assays are required whenever a new structural feature is probed. Here, we describe a new mass-spectrometry-based workflow for enhanced structural lipidomics that, in a single experiment, can yield almost complete structural information for a given glycerophospholipid (GPL) species. This includes the lipid's sum (Brutto) composition from the accurate mass measured for the intact lipid ion and the characteristic headgroup fragment, the regioisomer composition from fragment ions unique to the sn-1 and sn-2 positions, and the positions of carbon-carbon double bonds in the lipid acyl chains. Here, lipid ions are fragmented using electron impact excitation of ions from organics (EIEIO)-a technique where the singly charged lipid ions are irradiated by an electron beam, producing diagnostic product ions. We have evaluated this methodology on various lipid standards, as well as on a biological extract, to demonstrate this new method's utility. © 2015 American Chemical Society.

Kochmann S.,York University | Agostino F.J.,York University | Leblanc J.C.Y.,SCIEX | Krylov S.N.,York University
Analytical Chemistry | Year: 2016

In this technical note, we demonstrate the hyphenation of production-scale free-flow electrophoresis (FFE) and sheathless electrospray ionization mass spectrometry (ESI-MS). In contrast to previous hyphenation approaches, we used a highly conductive background electrolyte (BGE) required for production-scale FFE. We found that this kind of BGE as well as a production-scale setup leads to significant electric interference between FFE and MS. This interference prevents steady-state FFE operation. We examine this interference in detail and discuss possible solutions to this issue. We demonstrate that the straightforward grounding of the transfer line removes the influence of ESI-MS on FFE, but creates a current leak from the ESI interface, which adversely affects the ESI spray. Furthermore, we show that only the electrical disconnection of the ESI probe from the FFE-MS transfer line suppresses this undesirable current. In order to facilitate the electrical disconnection we used a low conductivity, silica-based ESI probe with withdrawn inner capillary. This approach allowed the interference-free hyphenation of production-scale FFE (using a highly conductive BGE) with ESI-MS. © 2016 American Chemical Society.

Jian W.,Pharmacokinetics | Kang L.,Pharmacokinetics | Burton L.,SCIEX | Weng N.,Pharmacokinetics
Bioanalysis | Year: 2016

Aim: The commonly used LC-MS workflow to quantify protein therapeutics in biological samples is 'bottom-up' approach. In this study, the aim is to establish 'top-down' approach for absolute quantitation of therapeutic antibodies or proteins of similar sizes in biological samples at intact level. Materials and methods: Using a recombinant human monoclonal antibody as the model molecule, we present a workflow to measure large therapeutic proteins in plasma at intact level based on deconvoluted high-resolution MS (HRMS) peaks. A novel MultiQuant™ software function was developed to automatically deconvolute the peaks and process the data. Results and conclusion: The workflow showed satisfying performance. This is a proof of concept study demonstrating the feasibility of bioanalysis of large therapeutic proteins at intact level using LC-HRMS. © 2016 Future Science Ltd.

Noestheden M.,SCIEXON | Roberts S.,SCIEX | Hao C.,Environment Canada
Rapid Communications in Mass Spectrometry | Year: 2016

Rationale: Neonicotinoid pesticides and their metabolites have been indicated as contributing factors in the decline of honey bee colonies. A thorough understanding of neonicotinoid toxicity requires knowledge of their metabolites and environmental breakdown products. This work investigated the rapid degradation of the neonicotinoid nitenpyram in finished drinking water. Methods: Nitenpyram reaction products were characterized using liquid chromatography/quadrupole time-of-flight mass spectrometry (LC/QTOFMS). A software algorithm that compared degraded and control samples was utilized to facilitate efficient data reduction. Fragmentation pathways for six reaction products and nitenpyram were proposed using predictive software and manual product ion analysis. Results: This study showed that nitenpyram degradation in unpreserved finished drinking water was likely the result of oxidation, hydrolysis and reaction with Cl2. Structures for six nitenpyram reaction products were proposed that suggest the C9/C11 olefin as the key reactive site. Conclusions: Similarities between the identified nitenpyram reaction products and imidacloprid metabolites highlight the importance of this study, as the toxicity of neonicotinoids to pollinators has been linked to their metabolites. Based on the proposed reaction mechanisms, the identified nitenpyram reaction products in finished drinking water could also be present in the environment and water treatment facilities. As such, identifying these degradation products will aid in evaluating the environmental impact of neonicotinoid pesticides. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Castaneto M.S.,U.S. National Institute on Drug Abuse | Castaneto M.S.,University of Maryland, Baltimore | Wohlfarth A.,U.S. National Institute on Drug Abuse | Pang S.,SCIEX | And 4 more authors.
Forensic Toxicology | Year: 2015

AB-FUBINACA, N-(1-amino-3-methyl-1-oxobutan-2-yl)-1-(4-fluorobenzyl)-1H-indazole-3-carboxamide, is an indazole synthetic cannabinoid identified in drug seizures around the world. Few metabolism data are available, despite the need for human urinary markers to detect AB-FUBINACA intake. Our main objective was to identify suitable analytical targets by analyzing human hepatocyte incubation samples with high-resolution mass spectrometry (HRMS) and to confirm the results in authentic urine specimens. We also determined AB-FUBINACA’s metabolic stability in human liver microsomes (HLMs) and compared hepatocyte and urine results with in silico predictions. The metabolic stability of AB-FUBINACA was determined in pooled HLMs (1 µmol/l, up to 1 h). The metabolite profile of human hepatocytes (10 µmol/l, 1 and 3 h) and urine samples from two subjects were determined by HRMS using information-dependent tandem-mass spectrometry (MS-MS) acquisition. Data were analyzed with MetabolitePilot™ software utilizing different processing algorithms, including generic peak finding, mass defect filtering, neutral loss, and product ion filtering. In silico metabolite prediction was performed with MetaSite™ software. AB-FUBINACA’s half-life in HLMs was 62.6 ± 4.0 min. AB-FUBINACA produced 11 metabolites (2 glucuronides) in human hepatocytes and 10 were identified in authentic human urine. Major metabolic pathways were terminal amide hydrolysis, acyl glucuronidation and hydroxylation at the aminooxobutane moiety. Epoxidation followed by hydrolysis, hydroxylation at the indazole moiety and dehydrogenation were minor pathways. Defluorination did not occur. Seventeen first-generation metabolites were predicted in silico, of which seven were observed in vitro and eight in vivo. We recommend AB-FUBINACA carboxylic acid, hydroxy AB-FUBINACA carboxylic acid, dihydrodiol AB-FUBINACA and dihydrodiol AB-FUBINACA carboxylic acid as suitable urinary markers. © 2015, Japanese Association of Forensic Toxicology and Springer Japan (outside the USA).

Noestheden M.R.,SCIEX
Journal of the Institute of Brewing | Year: 2015

Following recent studies that showed that the agrochemical mepiquat (1,1-dimethylpiperidinium) forms during the roasting of coffee beans and barley, this work investigates the presence of mepiquat in malted barley and commercially available beers. Liquid chromatography-tandem mass spectrometry was used to develop a sensitive and precise analytical method, with detection limits of 0.031 ng/g in malted barley and 0.014 ng/g in beer. Mepiquat was detected in nine out of 10 malted barley samples, with all results under the Canadian maximum residue limit (100 ng/g). The data suggest a relationship between perceived malted barley colour and mepiquat concentration. The concentration of mepiquat in the beers analysed was also below the maximum residue limits in Canada (100 ng/g) and in the EU (600 ng/g), suggesting that mepiquat is not a regulatory concern in finished beers. © 2015 The Institute of Brewing & Distilling.

News Article | October 28, 2016

The structure of chromatin is critical for many aspects of cellular physiology and is considered to be the primary medium to store epigenetic information. The nucleosomes together with the non-histone proteins define a stable chromatin structure. Regardless of its stability, this structure is disassembled and reassembled during DNA replication, repair, recombination or transcription. During all those processes, defined chromatin regions become accessible to be bound by the required factors, resulting in extensive nucleosome turnover at given genomic loci. The dual nature of chromatin requires a continuous interplay between stable and dynamic structures, which has to be coordinated at the molecular level to maintain the epigenetic information stored in the chromatin structure. Despite the biological relevance of these processes, little is known about the order of chromatin assembly steps, the molecular mechanisms that coordinate the required cellular machinery in time and the quality control of this assembly. To address these questions, the team at the biomedical center of the LMU uses an in-vitro system that resembles the formation of chromatin on double-stranded DNA. This in-vitro system not only enables researchers to dissect critical steps of assembly, but also to verify predictions based on previously published data on proteomic analysis of captured nascent chromatin (NCC) in living cells. SCIEX will sponsor this free webinar on the implementation of label free quantitative SWATH-MS at different assembly times, enabling the identification of distinct aspects of chromatin assembly such as the appearance and disappearance of histone modifications. Two researches from Ludwig Maximilian University (LMU) in Munich present during this webinar, PhD candidate, Moritz Völker-Albert and Dr. Andreas Schmidt. As PhD student in the chromatin proteomics group at the LMU, Moritz Völker-Albert investigates the kinetics of chromatin assembly. Prior to starting his doctorate in Munich in 2013, Völker-Albert completed his master’s degree in biomedical sciences at the Universities of Leiden and Utrecht in the Netherlands. During his studies, he focused on several aspects of chromatin research like chromatin remodeling assays, DNA repair and proteomic analysis of chromatin complexes. Andreas Schmidt earned his doctorate degree from University of Vienna, where he studied phosphorylation of arginine as stress-induced protein tag in bacteria. In collaboration with the group of T. Clausen, the team described the protein arginine kinase and improved enrichment and identification of peptides with this modification. Since 2013, he has worked as PostDoc for development of protocols for proteomics analysis and proteomics data analysis at the Department of Molecular Biology of the Medical Faculty of the LMU. The focus of his work is development of data independent acquisition methods for quantitation of proteins and protein modifications as well as improving the data analysis of data-independent mass spectrometry data. LabRoots will host the webinar on November 23, 2016, beginning at 8:00 a.m. PT, 11:00 a.m. ET. To read full event details or register for free, click here. About SCIEX: SCIEX helps to improve the world we live in by enabling scientists and laboratory analysts to find answers to the complex analytical challenges they face. The company's global leadership and world-class service and support in the capillary electrophoresis and liquid chromatography-mass spectrometry industry have made it a trusted partner to thousands of the scientists and lab analysts worldwide who are focused on basic research, drug discovery and development, food and environmental testing, forensics and clinical research. With over 40 years of proven innovation, SCIEX excels by listening to and understanding the ever-evolving needs of its customers to develop reliable, sensitive and intuitive solutions that continue to redefine what is achievable in routine and complex analysis. For more information, please visit About LabRoots: LabRoots is the leading scientific social networking website and producer of educational virtual events and webinars. Contributing to the advancement of science through content sharing capabilities, LabRoots is a powerful advocate in amplifying global networks and communities. Founded in 2008, LabRoots emphasizes digital innovation in scientific collaboration and learning, and is a primary source for current scientific news, webinars, virtual conferences, and more. LabRoots has grown into the world’s largest series of virtual events within the Life Sciences and Clinical Diagnostics community.

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