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Framingham Center, MA, United States

Scheidweiler K.B.,U.S. National Institute on Drug Abuse | Jarvis M.J.Y.,AB SCIEX | Huestis M.A.,U.S. National Institute on Drug Abuse
Analytical and Bioanalytical Chemistry | Year: 2015

Clandestine laboratories constantly produce new synthetic cannabinoids to circumvent legislative scheduling efforts, challenging and complicating toxicological analysis. Sundstrom et al. (Anal Bioanal Chem 405(26):8463-8474, [9]) and Kronstrand et al. (Anal Bioanal Chem 406(15):3599-3609, [10]) published nontargeted liquid chromatography, high-resolution, quadrupole/time-of-flight mass spectrometric (LC-QTOF) assays with validated detection of 18 and 38 urinary synthetic cannabinoid metabolites, respectively. We developed and validated a LC-QTOF urine method for simultaneously identifying the most current 47 synthetic cannabinoid metabolites from 21 synthetic cannabinoid families (5-fluoro AB-PINACA, 5-fluoro-AKB48, 5-fluoro PB-22, AB-PINACA, ADB-PINACA, AKB48, AM2201, JWH-018, JWH-019, JWH-073, JWH-081, JWH-122, JWH-200, JWH-210, JWH-250, JWH-398, MAM2201, PB-22, RCS-4, UR-144, and XLR11). β-Glucuronidase-hydrolyzed urine was extracted with 1-mL Biotage SLE+ columns. Specimens were reconstituted in 150-μL mobile phase consisting of 80 % A (0.1 % formic acid in water) and 20 % B (0.1 % formic acid in acetonitrile). Fifty microliters was injected, and SWATH™ MS data were acquired in positive electrospray mode. The LC-QTOF instrument consisted of a Shimadzu UFLCxr system and an ABSciex 5600+ TripleTOF® mass spectrometer. Gradient chromatographic separation was achieved with a Restek Ultra Biphenyl column with a 0.5-mL/min flow rate and an overall run time of 15 min. Identification criteria included molecular ion mass error, isotopic profiles, retention time, and library fit criteria. Limits of detection were 0.25-5 μg/L (N=10 unique fortified urine samples), except for two PB-22 metabolites with limits of 10 and 20 μg/L. Extraction efficiencies and matrix effects (N=10) were 55-104 and -65-107 %, respectively. We present a highly useful novel LC-QTOF method for simultaneously confirming 47 synthetic cannabinoid metabolites in human urine. © 2014 Springer-Verlag.

Ramagiri S.,AB SCIEX | Garofolo F.,Algorithme Pharma Inc.
Bioanalysis | Year: 2012

Background: Recent developments in LC-MS have turned it into a viable and valid alternative to ligand-binding assays. Large molecule bioanalysis by LC-MS is generally performed by tryptic digestion, purification and detection of one or more small signature peptides. High-resolution MS instruments offer quantification of intact small proteins or peptides and are able to increase the selectivity, while maintaining sensitivity. Results: Unlike multiple reaction monitoring assays, several factors affecting data processing were presented and the optimal parameters to consider during quantification method building were also demonstrated. MUC5AC-13 (MW 1709.8 Da), human hepcidin/LEAP-1 (MW 2797.4 Da), porcine calcitonin (MW 3604 Da) and chicken lysozyme (MW 14.3 kDa) were selected as model compounds and the possibility of intact peptide and small protein quantification, without tryptic digestion, was demonstrated. Conclusion: Selectivity and sensitivity were improved using different scan modes, such as TOF-MS and TOF-MS/MS. © 2012 Future Science Ltd.

Campbell J.L.,AB SCIEX
Rapid Communications in Mass Spectrometry | Year: 2010

Atmospheric pressure ionization (API) sources have the ability to serve as dynamic 'reaction vessels' and this capability has been rapidly evolving over the past few years. With API sources, many different reagents and source conditions can be rapidly explored with minimal carryover or contamination of the mass spectrometer. While most API applications involve the simple protonation/deprotonation of analyte molecules, a great deal of flexibility and utility is available in almost any API source, provided the reagents and ionization conditions are judiciously selected. Here, the generation of a unique and useful class of reagent ions at atmospheric pressure is demonstrated for the first time. Within the AP gas-phase environment of a dual inlet ion source, the gas-phase synthesis of substituted N-phenylpyridinium cations is demonstrated by establishing conditions favorable to the nucleophilic substitution reaction required for their formation. The flexibility of this API source as a reaction vessel is also demonstrated. Copyright © 2010 John Wiley & Sons, Ltd.

Poston C.N.,Brown University | Krishnan S.C.,AB SCIEX | Bazemore-Walker C.R.,Brown University
Journal of Proteomics | Year: 2013

The endoplasmic reticulum (ER) and mitochondria communicate via contact sites known as mitochondria-associated ER membranes or MAM. The region has emerged as the primary area of Ca2+ traffic between the two organelles, and as such, has been implicated in the regulation of protein folding, oxidative phosphorylation, and Ca2+-mediated apoptosis. In order to better understand biological processes and molecular functions at the MAM, we report a global mass spectrometry-based proteomic evaluation of the MAM obtained from mouse brain samples. Gel-assisted sample preparation in conjunction with our two-dimensional chromatography approach allowed for the identification of 1,212 high confidence proteins. Bioinformatic interrogation of this protein catalogue using Ingenuity Pathway Analysis revealed new potential connections between our list of MAM proteins and neurodegenerative diseases in addition to anticipated biological processes. Based on our results, we postulate that proteins of the MAM may play essential roles in dysfunctions responsible for several neurological disorders in addition to facilitating key cellular survival processes. © 2012 Elsevier B.V.

Campbell J.L.,AB SCIEX | Zhu M.,University of Waterloo | Hopkins W.S.,University of Waterloo
Journal of the American Society for Mass Spectrometry | Year: 2014

(Figure Presented) Differential mobility spectrometry (DMS) can distinguish ions based upon the differences in their high- and low-field ion mobilities as they experience the asymmetric waveform applied to the DMS cell. These mobilities are known to be influenced by the ions' structure, m/z, and charge distribution (i.e., resonance structures) within the ions themselves, as well as by the gas-phase environment of the DMS cell. While these associations have been developed over time through empirical observations, the exact role of ion structures or their interactions with clustering molecules remains generally unknown. In this study, that relationship is explored by observing the DMS behaviors of a series of tetraalkylammonium ions as a function of their structures and the gas-phase environment of the DMS cell. To support the DMS experiments, the basin-hopping search strategy was employed to identify candidate cluster structures for density functional theory treatment. More than a million cluster structures distributed across 72 different ion-molecule cluster systems were sampled to determine global minimum structures and cluster binding energies. This joint computational and experimental approach suggests that cluster geometry, in particular ion-molecule intermolecular separation, plays a critical role in DMS. © 2014 American Society for Mass Spectrometry.

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