Last data update: Sep 16, 2024. (Total: 47680 publications since 2009)
Records 1-3 (of 3 Records) |
Query Trace: Johnson Rudolph C [original query] |
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Structural Characterization and Absolute Quantification of Microcystin Peptides Using Collision-Induced and Ultraviolet Photo-Dissociation Tandem Mass Spectrometry.
Attard TJ , Carter MD , Fang M , Johnson RC , Reid GE . J Am Soc Mass Spectrom 2018 29 (9) 1812-1825 Microcystin (MC) peptides produced by cyanobacteria pose a hepatotoxic threat to human health upon ingestion from contaminated drinking water. While rapid MC identification and quantification in contaminated body fluids or tissue samples is important for patient treatment and outcomes, conventional immunoassay-based measurement strategies typically lack the specificity required for unambiguous determination of specific MC variants, whose toxicity can significantly vary depending on their structures. Furthermore, the unambiguous identification and accurate quantitation of MC variants using tandem mass spectrometry (MS/MS)-based methods can be limited due to a current lack of appropriate stable isotope-labeled internal standards. To address these limitations, we have systematically examined here the sequence and charge state dependence to the formation and absolute abundance of both "global" and "variant-specific" product ions from representative MC-LR, MC-YR, MC-RR, and MC-LA peptides, using higher-energy collisional dissociation (HCD)-MS/MS, ion-trap collision-induced dissociation (CID)-MS/MS and CID-MS(3), and 193 nm ultraviolet photodissociation (UPVD)-MS/MS. HCD-MS/MS was found to provide the greatest detection sensitivity for both global and variant-specific product ions in each of the MC variants, except for MC-YR where a variant-specific product uniquely formed via UPVD-MS/MS was observed with the greatest absolute abundance. A simple methodology for the preparation and characterization of (18)O-stable isotope-labeled MC reference materials for use as internal standards was also developed. Finally, we have demonstrated the applicability of the methods developed herein for absolute quantification of MC-LR present in human urine samples, using capillary scale liquid chromatography coupled with ultra-high resolution / accurate mass spectrometry and HCD-MS/MS. Graphical abstract . |
Naturally Occurring Genetic Variants of Human Acetylcholinesterase and Butyrylcholinesterase and Their Potential Impact on the Risk of Toxicity from Cholinesterase Inhibitors.
Lockridge O , Norgren RB Jr , Johnson RC , Blake TA . Chem Res Toxicol 2016 29 (9) 1381-92 Acetylcholinesterase (AChE) is the physiologically important target for organophosphorus toxicants (OP) including nerve agents and pesticides. Butyrylcholinesterase (BChE) in blood serves as a bioscavenger that protects AChE in nerve synapses from inhibition by OP. Mass spectrometry methods can detect exposure to OP by measuring adducts on the active site serine of plasma BChE. Genetic variants of human AChE and BChE do exist, but loss of function mutations have been identified only in the BCHE gene. The most common AChE variant, His353Asn (H322N), also known as the Yt blood group antigen, has normal AChE activity. The most common BChE variant, Ala567Thr (A539T) or the K-variant in honor of Werner Kalow, has 33% reduced plasma BChE activity. The genetic variant most frequently associated with prolonged response to muscle relaxants, Asp98Gly (D70G) or atypical BChE, has reduced activity and reduced enzyme concentration. Early studies in young, healthy males, performed at a time when it was legal to test nerve agents in humans, showed that individuals responded differently to the same low dose of sarin with toxic symptoms ranging in severity from minimal to moderate. Additionally, animal studies indicated that BChE protects from toxicants that have a higher reactivity with AChE than with BChE (e.g., nerve agents) but not from toxicants that have a higher reactivity with BChE than with AChE (e.g., OP pesticides). As a corollary, we hypothesize that individuals with genetic variants of BChE may be at increased risk of toxicity from nerve agents but not from OP pesticides. |
Stability of ricinine, abrine, and alpha-amanitin in finished tap water
Knaack Jennifer S , Pittman Christopher T , Wooten Joe V , Jacob Justin T , Magnuson Matthew , Silvestri Erin , Johnson Rudolph C . Anal Methods 2013 5 (20) 5804-5811 Ricinine and abrine are potential indicators of drinking water contamination by ricin and abrin, respectively. Simultaneous detection of ricinine and abrine, along with -amanitin, another potential biotoxin water contaminant, is reportable through the use of automated sample preparation via solid phase extraction and detection using liquid chromatography/tandem- mass spectrometry. Performance of the method was characterized over eight analytical batches with quality control samples analyzed over 10 days. For solutions of analytes prepared with appropriate preservatives, the minimum reporting level (MRL) was 0.50 g L-1 for ricinine and abrine and 2.0 g L-1 for -amanitin. Among the analytes, the accuracy of the analysis ranged between 93 and 100% at concentrations of 1-2.5x the MRL, with analytical precision ranging from 4 to 8%. Five drinking waters representing a range of water quality parameters and disinfection practices were fortified with the analytes and analyzed over a 28 day period to determine their storage stability in these waters. The analytical signal from ricinine was observed to be stable for 28 days after being spiked into all tap waters investigated. The analytical signal for abrine and -amanitin decreased within 5 h after these analytes were spiked into some drinking waters, but afterwards, remained stable for 28 days. The magnitude of the decrease correlated with common water quality parameters potentially related to sorption of contaminants onto dissolved and colloidal components within the particular water. Even with the decrease, the detectability offered by the method may be 100-1000 times greater than potential toxicological benchmarks, suggesting the utility of the method for all three analytes, with additional quality control precautions for abrine and -amanitin. 2013 The Royal Society of Chemistry. |
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