| 1. |
- Andersson, Maria, et al.
(författare)
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Metabolic profiling of new synthetic cannabinoids AMB and 5F-AMB by human hepatocyte and liver microsome incubations and high-resolution mass spectrometry
- 2016
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Ingår i: Rapid Communications in Mass Spectrometry. - : WILEY-BLACKWELL. - 0951-4198 .- 1097-0231. ; 30:8, s. 1067-1078
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Tidskriftsartikel (refereegranskat)abstract
- RationaleAMB (methyl (1-pentyl-1H-indazole-3-carbonyl)-L-valinate)) and its fluoro analog 5F-AMB (methyl (1-(5-fluoropentyl)-1H-indazole-3-carbonyl)-L-valinate) are two new synthetic cannabinoids that are structural analogs of AB-PINACA and 5F-AB-PINACA, respectively. 5F-AMB is scheduled as an illicit drug in China, Germany, Singapore and Japan, and no metabolism data are currently available for either drug. The aim of the present work was to investigate the metabolism of AMB and 5F-AMB and propose appropriate markers to identify their intake in clinical or forensic cases. MethodsAMB and 5F-AMB were incubated in human hepatocytes (10 mol/L) to generate phase I and II metabolites, which were identified with a TripleTOF 5600(+) high-resolution mass spectrometer. AMB and 5F-AMB metabolic stability studies also were performed with human liver microsomes (HLM) to evaluate metabolic clearances, and to adequately design the human hepatocyte experiment. ResultsAMB and 5F-AMB were quickly metabolized in HLM with a 1.1 0.1 and 1.0 +/- 0.2min T-1/2, respectively. The predominant metabolic pathway for AMB and 5F-AMB in hepatocytes was ester hydrolysis, and further oxidation and/or glucuronidation. In total, 19 metabolites were identified for AMB and 17 for 5F-AMB. We describe metabolites to differentiate AMB from 5F-AMB, and metabolites that are common to both analytes due to oxidative defluorination of 5F-AMB. ConclusionsFor the first time, AMB and 5F-AMB metabolism profiles were characterized, providing valuable data for identifying these two novel psychoactive substances. The difficulties of differentiating AMB and 5F-AMB from AB-PINACA/5F-AB-PINACA metabolites also were examined. These data improve the interpretation of urinary markers after AMB and 5F-AMB intake. Published in 2016. This article is a U.S. Government work and is in the public domain in the USA
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| 2. |
- Bohlin, Madeleine, et al.
(författare)
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High-precision determination of lithium and magnesium isotopes utilising single column separation and multi-collector inductively coupled plasma mass spectrometry
- 2018
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Ingår i: Rapid Communications in Mass Spectrometry. - : Wiley. - 0951-4198 .- 1097-0231. ; 32:2, s. 93-104
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Tidskriftsartikel (refereegranskat)abstract
- Rationale Li and Mg isotopes are increasingly used as a combined tool within the geosciences. However, established methods require separate sample purification protocols utilising several column separation procedures. This study presents a single-step cation-exchange method for quantitative separation of trace levels of Li and Mg from multiple sample matrices.Methods The column method utilises the macro-porous AGMP-50 resin and a high-aspect ratio column, allowing quantitative separation of Li and Mg from natural waters, sediments, rocks and carbonate matrices following the same elution protocol. High-precision isotope determination was conducted by multi-collector inductively coupled plasma mass spectrometry (MC-ICPMS) on the Thermo Scientific NEPTUNE Plus fitted with 1013Ω amplifiers which allow accurate and precise measurements at ion beams <0.51 V.Results Sub-nanogram Li samples (0.3-0.5 ng) were regularly separated (yielding Mg masses of 1-70 μg) using the presented column method. The total sample consumption during isotopic analysis is <0.5 ng Li and <115 ng Mg with long-term external 2σ precisions of ±0.39‰ for δ7Li and ±0.07‰ for δ26Mg. The results for geological reference standards and seawater analysed by our method are in excellent agreement with published values despite the order of magnitude lower sample consumption. Conclusions The possibility of eluting small sample masses and the low analytical sample consumption make this method ideal for samples of limited mass or low Li concentration, such as foraminifera, mineral separates or dilute river waters.
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| 3. |
- Chartrand, Michelle, et al.
(författare)
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Compound specific isotope analysis of hexachlorocyclohexane isomers : a method for source fingerprinting and field investigation of in situ biodegradation
- 2015
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Ingår i: Rapid Communications in Mass Spectrometry. - : John Wiley & Sons. - 0951-4198 .- 1097-0231. ; 29:6, s. 505-514
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Tidskriftsartikel (refereegranskat)abstract
- RATIONALE: The manufacturing and uses of hexachlorocyclohexane (HCH) have resulted in a serious environmentalchallenge and legacy. This study highlights the ability of compound specific isotope analysis (CSIA) to distinguishamong various HCH sources and to support the evaluation of the potential for in situ biodegradation in contaminatedgroundwater.METHODS: Tests were conducted to verify the absence of significant isotope fractionation during HCH sample preconcentrationincluding dichloromethane extraction, solvent exchange into iso-octane, and H2SO4 clean-up, and analysisby gas chromatography/combustion-isotope ratio mass spectrometry (GC/C-IRMS). The method was then applied tofour Technical Grade (TG) HCH mixtures procured from different sources and to groundwater samples from acontaminated site.RESULTS: The pre-concentration method enabled determination of carbon isotope ratios (δ13C values) of HCH isomerswith no significant isotopic fractionation. The TG-HCH mixtures had significantly different δ13C values. Moreover, forany given TG-HCH, all isomers had δ13C values within 1.1‰ of each other – a distinctly uniform fingerprint. At theHCH-contaminated field site, compared with source wells, downgradient wells showed significant (up to 5.1‰)enrichment in 13C and the δ13C values of the HCH isomers were significantly different from each other.CONCLUSIONS: A method was successfully developed for the CSIA of HCH isomers that showed potential for HCHsource differentiation and identification of HCH in situ biodegradation. At the HCH-contaminated site, the observedpreferential isotopic enrichment of certain isomers relative to others for a given source allows differentiation betweenbiodegraded and non-biodegraded HCH.
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| 4. |
- Glykou, Aikaterini, et al.
(författare)
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Intra- and inter-tooth variation in strontium isotope ratios from prehistoric seals by laser ablation multi-collector inductively coupled plasma mass spectrometry
- 2018
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Ingår i: Rapid Communications in Mass Spectrometry. - : Wiley. - 0951-4198 .- 1097-0231. ; 32, s. 1215-1224
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Tidskriftsartikel (refereegranskat)abstract
- RationaleStrontium isotope ratios (87Sr/86Sr) in modern‐day marine environments are considered to be homogeneous (~0.7092). However, in the Baltic Sea, the Sr ratios are controlled by mixing seawater and continental drainage from major rivers discharging into the Baltic. This pilot study explores if variations in Sr can be detected in marine mammals from archaeological sites in the Baltic Sea. Methods87Sr/86Sr ratios were measured in tooth enamel from three seal species by laser ablation multi‐collector inductively coupled plasma mass spectrometry (LA‐MC‐ICP‐MS). The method enables micro‐sampling of solid materials. This is the first time that the method has been applied to marine samples from archaeological collections. ResultsThe analyses showed inter‐tooth 87Sr/86Sr variation suggesting that different ratios can be detected in different regions of the Baltic Sea. Furthermore, the intra‐tooth variation suggests possible different geographic origin or seasonal movement of seals within different regions in the Baltic Sea through their lifetime. ConclusionsThe method was successfully applied to archaeological marine samples showing that: (1) the 87Sr/86Sr ratio in marine environments is not uniform, (2) 87Sr/86Sr differences might reflect differences in ecology and life history of different seal species, and (3) archaeological mobility studies based on 87Sr/86Sr ratios in humans should therefore be evaluated together with diet reconstruction.
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| 5. |
- Hansson, Annelie, et al.
(författare)
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Investigation of the selective androgen receptor modulators S1, S4 and S22 and their metabolites in equine plasma using high-resolution mass spectrometry
- 2016
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Ingår i: Rapid Communications in Mass Spectrometry. - : Wiley. - 0951-4198 .- 1097-0231. ; 30:7, s. 833-842
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Tidskriftsartikel (refereegranskat)abstract
- RationaleSelective androgen receptor modulators (SARMs) are prohibited in sports due to their performance enhancing ability. It is important to investigate the metabolism to determine appropriate targets for doping control. This is the first study where the equine metabolites of SARMs S1, S4 (Andarine) and S22 (Ostarine) have been studied in plasma. MethodsEach SARM was administered to three horses as an intravenous bolus dose and plasma samples were collected. The samples were pretreated with protein precipitation using cold acetonitrile before separation by liquid chromatography. The mass spectrometric analysis was performed using negative electrospray, quadrupole time-of-flight mass spectrometry operated in MSE mode and triple-quadrupole mass spectrometry operated in selected reaction monitoring mode. For the quantification of SARM S1, a deuterated analogue was used as internal standard. ResultsThe numbers of observed metabolites were eight, nine and four for the SARMs S1, S4 and S22, respectively. The major metabolite was formed by the same metabolic reactions for all three SARMs, namely amide hydrolysis, hydroxylation and sulfonation. The values of the determined maximum plasma concentrations were in the range of 97-170 ng/mL for SARM S1, 95-115 ng/mL for SARM S4 and 92-147 ng/mL for SARM S22 and the compounds could be detected for 96 h, 12 h and 18 h, respectively. ConclusionsThe maximum plasma concentration of SARMs S1, S4 and S22 was measured in the first sample (5 min) after administration and they were eliminated fast from plasma. The proposed targets to be used in equine doping control are the parent compounds for all three SARMs, but with the metabolite yielding the highest response as a complementary target.
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| 6. |
- Mashayekhy Rad, Farshid, et al.
(författare)
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Investigation of ultrahigh-performance liquid chromatography/travelling-wave ion mobility/time-of-flight mass spectrometry for fast profiling of fatty acids in the high Arctic sea surface microlayer
- 2018
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Ingår i: Rapid Communications in Mass Spectrometry. - : Wiley. - 0951-4198 .- 1097-0231. ; 32:12, s. 942-950
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Tidskriftsartikel (refereegranskat)abstract
- RationaleFatty acids are enriched in the ocean surface microlayer (SML) and have as a consequence been detected worldwide in sea spray aerosols. In searching for a relationship between the properties of the atmospheric aerosol and its ability to form cloud condensation nuclei and to promote cloud droplet formation over remote marine areas, the role of surface active fatty acids sourced from the SML is of interest to be investigated. Here is presented a fast method for profiling of major fatty acids in SML samples collected in the high Arctic (89 °N, 1 °W) in the summer of 2001.MethodsUHPLC/travelling‐wave ion mobility spectrometry (TWIMS)/time‐of‐flight (TOF) mass spectrometry (MS) for profiling was evaluated and compared with UHPLC/TOFMS. No sample preparation, except evaporation and centrifugation, was necessary to perform prior to the analysis.ResultsTOFMS data on accurate mass, isotopic ratios and fragmentation patterns enabled identification of the fatty acids. The TWIMS dimension added to the selectivity by extensive reduction of the noise level and the entire UHPLC/TWIMS/TOFMS method provided a fast profiling of the acids, ranging from C8 to C24. Hexadecanoic and octadecanoic acids were shown to yield the highest signals among the fatty acids detected in a high Arctic SML sample, followed by the unsaturated octadecenoic and octadecadienoic acids. The predominance of signal from even‐numbered carbon chains indicates a mainly biogenic origin of the detected fatty acids.ConclusionsThis study presents a fast alternative method for screening and profiling of fatty acids, which has the advantage of not requiring any complicated sample preparation thus limiting the loss of analytes. Almost no manual handling, together with the very small sample volumes needed, is certainly beneficial for the determination of trace amounts and should open up the field of applications to also include atmospheric aerosol and fog.
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| 7. |
- Miska, Milena E., et al.
(författare)
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Stable chlorine isotope analysis of chlorinated acetic acids using gas chromatography/quadrupole mass spectrometry
- 2015
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Ingår i: Rapid Communications in Mass Spectrometry. - : Wiley. - 0951-4198 .- 1097-0231. ; 29:24, s. 2341-2348
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Tidskriftsartikel (refereegranskat)abstract
- RationaleThe environmental occurrence of chlorinated acetic acids (CAAs) has been extensively studied, but the sources and transport are still not yet fully understood. A promising approach for source apportionment and process studies is the isotopic characterization of target compounds. We present the first on-line stable chlorine isotope analysis of CAAs by use of gas chromatography/quadrupole mass spectrometry (GC/qMS). MethodsFollowing approved procedures for concentration analysis, CAAs extracted into MTBE were methylated to GC-amenable methyl esters (mCAAs). These mCAAs were then analyzed by GC/qMS for their stable chlorine isotope composition using a sample/standard-bracketing approach (CAA standards in the range Cl-37 -6.3 to -0.2 , Standard Mean Ocean Chloride). ResultsCross-calibration of the herein presented method with off-line reference methods (thermal ionization and continuous-flow GC isotope ratio mass spectrometry; TI-MS and CF-GC/IRMS, respectively) shows good agreement between the methods (regression slope for GC/qMS vs reference method data sets: 0.92 +/- 0.29). Sample amounts as small as 10 pmol Cl can herewith be analyzed with a precision of 0.1 to 0.4 parts per thousand. ConclusionsThis method should be useful for environmental studies of CAAs at ambient concentrations in precipitations (<0.06 to 100nmolL(-1)), surface waters (<0.2 to 5nmolL(-1)) and soil (<0.6 to 2000nmolkg(-1) dry soil) where conventional off-line methods cannot be applied.
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| 8. |
- Nilsson, Jan
(författare)
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Tests of size and growth effects on Arctic charr (Salvelinus alpinus) otolith O-18 and C-13 values
- 2018
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Ingår i: Rapid Communications in Mass Spectrometry. - : Wiley. - 0951-4198 .- 1097-0231. ; 32, s. 1557-1564
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Tidskriftsartikel (refereegranskat)abstract
- RationaleOtolith O-18 and C-13 values have been used extensively to reconstruct thermal and diet histories. Researchers have suggested that individual growth rate and size may have an effect on otolith isotope ratios and subsequently confound otolith-based thermal and diet reconstructions. As few explicit tests of the effect on fish in freshwater environments exist, here we determine experimentally the potential for related growth rate and size effects on otolith O-18 and C-13 values.MethodsFifty Arctic charr were raised in identical conditions for two years after which their otoliths were removed and analyzed for their O-18 and C-13 values. The potential effects of final length and the Thermal Growth Coefficient (TGC) on otolith isotope ratios were tested using correlation and regression analysis to determine if significant effects were present and to quantify effects when present.ResultsThe analyses indicated that TGC and size had significant and similar positive non-linear relationships with C-13 values and explained 35% and 42% of the variability, respectively. Conversely, both TGC and size were found to have no significant correlation with otolith O-18 values. There was no significant correlation between O-18 and C-13 values.ConclusionsThe investigation indicated the presence of linked growth rate and size effects on otolith C-13 values, the nature of which requires further study. Otolith O-18 values were unaffected by individual growth rate and size, confirming the applicability of these values to thermal reconstructions of fish habitat.
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| 9. |
- Samgina, Tatiana Yu., et al.
(författare)
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LTQ Orbitrap Velos in routine de novo sequencing of non-tryptic skin peptides from the frog Rana latastei with traditional and reliable manual spectra interpretation
- 2016
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Ingår i: Rapid Communications in Mass Spectrometry. - : Wiley. - 0951-4198 .- 1097-0231. ; 30:2, s. 265-276
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Tidskriftsartikel (refereegranskat)abstract
- RATIONALE: Mass spectrometry has shown itself to be the most efficient tool for the sequencing of peptides. However, de novo sequencing of novel natural peptides is significantly more challenging in comparison with the same procedure applied for the tryptic peptides. To reach the goal in this case it is essential to select the most efficient methods of triggering fragmentation and combine all the possible complementary techniques. METHODS: Collision-induced dissociation (CID), high-energy collision dissociation (HCD), and electron-transfer dissociation (ETD) tandem mass spectra recorded with a LTQ Orbitrap Velos instrument were used for the elucidation of the sequence of the natural non-tryptic peptides from the skin secretion of Rana latastei. Manual interpretation of the spectra was applied. RESULTS: The combined approach using CID, HCD, and ETD tandem mass spectra of the multiprotonated peptides in various charge states, as well as of their proteolytic fragments, allowed the sequences of seven novel peptides from the skin secretion of Rana latastei to be established. CONCLUSIONS: Manual mass spectrometry sequencing of natural non-tryptic peptides from the skin secretion of Rana latastei provided the opportunity to work successfully with these species and demonstrated once again its advantage over automatic approaches.
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| 10. |
- Sämfors, Sanna, 1987, et al.
(författare)
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Benefits of NaCl addition for time-of-flight secondary ion mass spectrometry analysis including the discrimination of diacylglyceride and triacylglyceride ions
- 2018
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Ingår i: Rapid Communications in Mass Spectrometry. - : Wiley. - 0951-4198 .- 1097-0231. ; 32:17, s. 1473-1480
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Tidskriftsartikel (refereegranskat)abstract
- RationaleDiacylglycerides (DAGs) and triacylglycerides (TAGs) are two important lipid classes present in all mammalian cells that share similar chemical structures but differ in biological function in cells and tissues. Differentiation of these two species during time-of-flight secondary ion mass spectrometry (ToF-SIMS) analysis is therefore important, but has been difficult due to the formation of DAG-like ions during the ionization process of TAGs. MethodsWe investigated the use of salt adduct formation as a quick and simple method to determine the origin of the DAG-like ions in ToF-SIMS spectra. NaCl was added to lipid standards of a DAG and a TAG and differences in fragmentation patterns were identified. The salt was then applied to prepared tissue samples by spraying with a saturated solution of NaCl in methanol and samples were analysed with ToF-SIMS using a 40keV (CO2)(6k)(+) primary ion beam. ResultsA 40Da peak shift was observed in the DAG spectrum that was not observed in the TAG spectrum ([M+H-H2O](+) to [M+Na](+)) while the isobaric [M-RCOO](+) peak did not shift allowing differentiation between the two species. Spraying NaCl on to tissue sections indicated that the DAG-like ions originated from TAGs. ConclusionsWith the method described in this paper, simple addition of salt by spraying on the sample leads to better interpretation of complex mass spectra from biological tissue samples, discriminating DAG and TAG fragment peaks.
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| 11. |
- Thevis, Mario, et al.
(författare)
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Characterization of a non-approved selective androgen receptor modulator drug candidate sold via the Internet and identification of in vitro generated phase-I metabolites for human sports drug testing
- 2015
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Ingår i: Rapid Communications in Mass Spectrometry. - : Wiley. - 0951-4198 .- 1097-0231. ; 29:11, s. 991-999
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Tidskriftsartikel (refereegranskat)abstract
- RATIONALE: Potentially performance-enhancing agents, particularly anabolic agents, are advertised and distributed by Internet-based suppliers to a substantial extent. Among these anabolic agents, a substance referred to as LGD-4033 has been made available, comprising the core structure of a class of selective androgen receptor modulators (SARMs). METHODS: In order to provide comprehensive analytical data for doping controls, the substance was obtained and characterized by nuclear magnetic resonance spectroscopy (NMR) and liquid chromatography/electrospray ionization high resolution/high accuracy tandem mass spectrometry (LC/ESI-HRMS). Following the identification of 4-(2-(2,2,2-trifluoro-1-hydroxyethyl) pyrrolidin-1-yl)-2-(trifluoromethyl) benzonitrile, the substance was subjected to in vitro metabolism studies employing human liver microsomes and Cunninghamella elegans (C. elegans) preparations as well as electrochemical metabolism simulations. RESULTS: By means of LC/ESI-HRMS, five main phase-I metabolites were identified as products of liver microsomal preparations including three monohydroxylated and two bishydroxylated species. The two most abundant metabolites (one mono-and one bishydroxylated product) were structurally confirmed by LC/ESI-HRMS and NMR. Comparing the metabolic conversion of 4-(2-(2,2,2-trifluoro-1-hydroxyethyl) pyrrolidin-1-yl)-2-(trifluoromethyl) benzonitrile observed in human liver microsomes with C. elegans and electrochemically derived metabolites, one monohydroxylated product was found to be predominantly formed in all three methodologies. CONCLUSIONS: The implementation of the intact SARM-like compound and its presumed urinary phase-I metabolites into routine doping controls is suggested to expand and complement existing sports drug testing methods.
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| 12. |
- Thevis, M., et al.
(författare)
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Nickel in equine sports drug testing - pilot study results on urinary nickel concentrations
- 2016
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Ingår i: Rapid Communications in Mass Spectrometry. - : Wiley. - 0951-4198 .- 1097-0231. ; 30:7, s. 982-984
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Tidskriftsartikel (refereegranskat)abstract
- RationaleThe issue of illicit performance enhancement spans human and animal sport in presumably equal measure, with prohibited substances and methods of doping conveying both ways. Due to the proven capability of unbound ionic cobalt (Co2+) to stimulate erythropoiesis in humans, both human and equine anti-doping regulations have listed cobalt as a banned substance, and in particular in horse drug testing, thresholds for cobalt concentrations applying to plasma and urine have been suggested or established. Recent reports about the finding of substantial amounts of undeclared nickel in arguably licit performance- and recovery-supporting products raised the question whether the ionic species of this transition metal (Ni2+), which exhibits similar prolyl hydroxylase inhibiting properties to Co2+, has been considered as a substitute for cobalt in doping regimens. MethodsTherefore, a pilot study with 200 routine post-competition doping control horse urine samples collected from animals participating in equestrian, gallop, and trotting in Europe was conducted to provide a first dataset on equine urinary Ni2+ concentrations. All specimens were analyzed by conventional inductively coupled plasma mass spectrometry (ICP-MS) to yield quantitative data for soluble nickel. ResultsConcentrations ranging from below the assay's limit of quantification (LOQ, 0.5 ng/mL) up to 33.4 ng/mL with a mean value ( standard deviation) of 6.1 (+/- 5.1) ng/mL were determined for the total nickel content. ConclusionsIn horses, nickel is considered a micronutrient and feed supplements containing nickel are available; hence, follow-up studies are deemed warranted to consolidate potential future threshold levels concerning urine and blood nickel concentrations in horses using larger sets of samples for both matrices and to provide in-depth insights by conducting elimination studies with soluble Ni2+-salt species.
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| 13. |
- Russell, C. L., et al.
(författare)
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Combined tissue and fluid proteomics with Tandem Mass Tags to identify low-abundance protein biomarkers of disease in peripheral body fluid: An Alzheimer's Disease case study
- 2017
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Ingår i: Rapid Communications in Mass Spectrometry. - : Wiley. - 0951-4198. ; 31:2, s. 153-159
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Tidskriftsartikel (refereegranskat)abstract
- RationaleIdeal biomarkers are present in readily accessible samples including plasma and cerebrospinal fluid (CSF), and are directly derived from diseased tissue, therefore likely to be of relatively low abundance. Traditional unbiased proteomic approaches for biomarker discovery have struggled to detect low-abundance markers due to the high dynamic range of proteins, the predominance of hyper-abundant proteins, and the use of data-dependent acquisition mass spectrometry (MS). To overcome these limitations and improve biomarker discovery in peripheral fluids, we have developed TMTcalibrator; a novel MS workflow combining isobarically labelled diseased tissue digests in parallel with an appropriate set of labelled body fluids to increase the chance of identifying low-abundance, tissue-derived biomarkers. MethodsA disease relevant cell line was labelled with TMT (R) in a range of concentrations generating a multi-point calibration curve. Peripheral biofluid samples were labelled with the remaining tags and quantitative analysis was performed using an Orbitrap Fusion Tribrid mass spectrometer with a Top10 CID-HCD MS3 synchronous precursor selection (SPS) method. SPS allowed direct analysis of non-depleted, unfractionated CSF samples with complete profiling of six individual samples requiring only 15hours of MS time, equivalent to 1.5h per sample. ResultsUsing the TMTcalibrator workflow allowed the identification of several markers of microglia activation that are differentially quantified in the CSF of patients with Alzheimer's disease (AD). We report peptides from 41 proteins that have not previously been detected in the CSF, that appear to be regulated by at least 60% in AD. ConclusionsThis study has demonstrated the benefits of the new TMTcalibrator workflow and the results suggest this is a suitable and efficient method of detecting low-abundance peptides within biological fluids. The use of TMTcalibrator in further biomarker discovery studies should be considered to overcome some of the limitations commonly associated with more conventional approaches.
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