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Electrospray Ionization (electrospray + ionization)
Kinds of Electrospray Ionization Terms modified by Electrospray Ionization Selected AbstractsESI+ MS/MS confirmation of canine ivermectin toxicity,JOURNAL OF MASS SPECTROMETRY (INCORP BIOLOGICAL MASS SPECTROMETRY), Issue 1 2009A. F. Lehner Abstract Ivermectin is a semisynthetic macrocyclic lactone anthelmintic of the avermectin family derived from Streptomyces fermentation products. Avermectins are used as antiparasitic agents in domestic animals; although considered relatively safe, one must consider animal species, breed, weight, and age in dosage determinations. In January 2006, two canines were presented to the UK Livestock Disease Diagnostic Center after dying from suspected ivermectin overdoses [30,50 mg/kg body weight]. To confirm this clinical diagnosis we developed a rapid, sensitive semiquantitative ElectroSpray Ionization,Mass Spectrometry (ESI/MS) method for ivermectin in canine tissue samples. Pharmaceutical ivermectin contains two ivermectins differing by a single methyl group, and each compound forms interpretation-confounding adducts with tissue Na+ and K+ ions. We now report that ivermectin administration was clearly confirmed by comparison with standard and dosage forms of ivermectin, and simple proportionalities based on mass spectral intensity of respective molecular ions allowed semiquantitative estimates of injection site tissue concentrations of 20 and 40 µg/g tissue (wet weight) in these animals, consistent with the history of ivermectin administration and the clinical signs observed. There is a distinct need for both rapid detection and confirmation of toxic exposures in veterinary diagnostics, whether for interpretation of clinical cases antemortem or for forensic reasons postmortem. It is vital that interpreters of analytical results have appropriate guidance in the scientific literature and elsewhere so as to enable clear-cut answers. The method presented here is suitable for routine diagnostic work in that it allows rapid extraction of ivermectin from tissue samples, avoids the need for high-performance liquid chromatography and allows ready interpretation of the multiple ivermectin species seen by ESI+ MS/MS in samples originating from veterinary dosage forms. Copyright © 2008 John Wiley & Sons, Ltd. [source] Direct injection horse-urine analysis for the quantification and confirmation of threshold substances for doping control.DRUG TESTING AND ANALYSIS, Issue 8 2009Abstract Levodopa and dopamine have been abused as performance-altering substances in horse racing. Urinary 3-methoxytyramine is used as an indicator of dopaminergic manipulation resulting from dopamine or levodopa administration and is prohibited with a urinary threshold of 4 µg mL,1 (free and conjugated). A simple liquid chromatographic (LC)/mass spectrometric (MS) (LCMS) method was developed and validated for the quantification and identification of 3-methoxytyramine in equine urine. Sample preparation involved enzymatic hydrolysis and protein precipitation. Hydrophilic interaction liquid chromatography (HILIC) was selected as a separation technique that allows effective retention of polar substances like 3-methoxytyramine and efficient separation from matrix compounds. Electrospray ionization (ESI) in positive mode with product ion scan mode was chosen for the detection of the analytes. Quantification of 3-methoxytyramine was performed with fragmentation at low collision energy, resulting in one product ion, while a second run at high collision energy was performed for confirmation (at least three abundant ions). Studies on matrix effects showed ion suppression depending on the horse urine used. To overcome the variability of the results originating from the matrix effects, isotopic labelled internal standard was used and linear regression calibration methodology was applied for the quantitative determination of the analyte. The tested linear range was 1,20 µg mL,1. The relative standard deviations of intra- and inter- assay analysis of 3-methoxytyramine in horse urine were lower than 4.2% and 3.2%, respectively. Overall accuracy (relative percentage error) was less than 6.2%. The method was applied to case samples, demonstrating simplicity, accuracy and selectivity. Copyright © 2009 John Wiley & Sons, Ltd. [source] Fragmentation of Alkoxo(catecholato)vanadium(V) Complexes[(C6H4O2)V(OR1)(OR2)]+ in the Gas PhaseEUROPEAN JOURNAL OF INORGANIC CHEMISTRY, Issue 14 2005Malgorzata Kaczorowska Abstract Electrospray ionization (ESI) mass spectrometry is used to investigate the gas-phase dissociation behavior of vanadium(V) complexes [(C6H4O2)V(OR1)(OR2)]+ containing two identical or different alkoxy groups (R1, R2 = CH3, C2H5, n -C3H7, i -C3H7 and t -C4H9) and a catecholato ligand (C6H4O2). The fragmentation reactions of the complexes are studied by collision-induced dissociation (CID) and labeling experiments. For [(C6H4O2)V(OR1)(OR2)]+ cations with alkoxo groups larger than methyl, a trend for preferential evaporation of hydrocarbon fragments is observed, followed by expulsion of neutral alcohols. Further, the CID spectra of all complexes show a signal which can be assigned to the complex [(C6H4O2)VO]+. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005) [source] Transition metals as electron traps.JOURNAL OF MASS SPECTROMETRY (INCORP BIOLOGICAL MASS SPECTROMETRY), Issue 10 2009Abstract Transition metal cations Co2+, Ni2+ and Zn2+ form 1 : 1 : 1 ternary complexes with 2,2,-bipyridine (bpy) and peptides in aqueous methanol solutions that have been studied for tripeptides GGG and GGL. Electrospray ionization of these solutions produced singly charged [Metal(bpy)(peptide , H)]+ and doubly charged [Metal(bpy)(peptide)]2+ ions (Metal = metal ion) that underwent charge reduction by glancing collisions with Cs atoms at 50 and 100 keV collision energies. Electron transfer to [Metal(bpy)(peptide)]2+ ions was less than 4.2 eV exoergic and formed abundant fractions of non-dissociated charge-reduced intermediates. Charge-reduced [Metal(bpy)(peptide)]+ ions dissociated by the loss of a hydrogen atom, ammonia, water and ligands that depended on the metal ion. The Ni and Co complexes mainly dissociated by the elimination of ammonia, water, and the peptide ligand. The Zn complex dissociated by the elimination of ammonia and bpy. A sequence-specific fragment was observed only for the Co complex. Electron transfer to [Metal(bpy)(peptide , H)]+ was 0.6,1.6 eV exoergic and formed intermediate radicals that were detected as stable anions after a second electron transfer from Cs. [Metal(bpy)(peptide , H)] neutrals and their anions dissociated by the loss of bpy and peptide ligands with branching ratios that depended on the metal ion. Optimized structures for several spin states, electron transfer and dissociation energies were addressed by combined density functional theory and Møller,Plesset perturbational calculations to aid interpretation of experimental data. The experimentally observed ligand loss and backbone cleavage in charge-reduced [Metal(bpy)(peptide)]+ complexes correlated with the dissociation energies at the present level of theory. The ligand loss in +CR, spectra showed overlap of dissociations in charge-reduced [Metal(bpy)(peptide , H)] complexes and their anionic counterparts which complicated spectra interpretation and correlation with calculated dissociation energies. Copyright © 2009 John Wiley & Sons, Ltd. [source] Characterization of the glycosidic linkage of underivatized disaccharides by interaction with Pb2+ ionsJOURNAL OF MASS SPECTROMETRY (INCORP BIOLOGICAL MASS SPECTROMETRY), Issue 8 2007Ahlam El Firdoussi Abstract Electrospray ionization in combination with tandem mass spectrometry and lead cationization is used to characterize the linkage position of underivatized disaccharides. Lead(II) ions react mainly with disaccharides by proton abstraction to generate [Pb(disaccharide)m, H]+ ions (m = 1,2). At low cone voltages, an intense series of doubly charged ions of general formula [Pb(disaccharide)n]2+ are also observed. Our study shows that MS/MS experiments have to be performed to differentiate Pb2+ -coordinated disaccharides. Upon collision, [Pb(disaccharide) , H]+ species mainly dissociate according to glycosidic bond cleavage and cross-ring cleavages, leading to the elimination of CnH2nOn neutrals (n = 2,4). The various fragmentation processes allow the position of the glycosidic bond to be unambiguously located. Distinction between glc-glc and glc-fru disaccharides also appears straightforward. Furthermore, for homodimers of D -glucose our data demonstrate that the anomericity of the glycosidic bond can be characterized for the 1 , n linkages (n = 2, 4, 6). Consequently, Pb2+ cationization combined with tandem mass spectrometry appears particularly useful to identify underivatized disaccharides. Copyright © 2007 John Wiley & Sons, Ltd. [source] Electrospray mass spectrometry of stable iminyl nitroxide and nitronyl nitroxide free radicalsJOURNAL OF MASS SPECTROMETRY (INCORP BIOLOGICAL MASS SPECTROMETRY), Issue 9 2002Craig D. Smith Abstract Electrospray ionization (ESI) mass spectra have been recorded for a range of substituted nitronyl nitroxide and iminyl nitroxide monoradicals and biradicals. Secondary species formed in the ESI source were observed as the dominant ions in both the iminyl nitroxide and nitronyl nitroxide spectra. Daughter ion spectrometry was used to establish fragmentation mechanisms for the nitronyl nitroxide and iminyl nitroxide moieties as well as the secondary species under ESI conditions. Copyright © 2002 John Wiley & Sons, Ltd. [source] Electrospray ionization and atmospheric pressure matrix-assisted laser desorption/ionization mass spectrometry of antioxidants applied in lubricants,RAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 24 2009Alexander Kassler The aim of this study was to investigate the utility of ion trap mass spectrometry (ITMS) in combination with the two desorption/ionization methods, electrospray (ESI) and atmospheric pressure matrix-assisted laser desorption/ionization (AP-MALDI), for the detection of antioxidants which are applied in lubricants. These experiments should form the base for future investigations of antioxidants in tribologically formed thin layers on the surface of frictional systems. Seventeen different antioxidants were selected out of the group of hindered phenolic and aromatic aminic compounds. Practically all antioxidants could be characterized by positive ion ESI- and AP-MALDI-ITMS, forming various types/species of molecular ions (e.g. [M]+., [M+H]+, [M+Na]+ or [M,2H+H]+). A few compounds could be analyzed by negative ion ESI-MS, too, but none by negative ion AP-MALDI-MS. The influence of target materials in AP-MALDI-MS (gold- and titanium nitride (TiN)-covered stainless steel, micro-diamond-covered hard metal, hand-polished and sand-blasted stainless steel targets) with respect to the molecular ion intensity and type of molecular ion of two selected antioxidants was evaluated. The surface properties are of particular interest because in friction tests different materials with different surface characteristics are used. However, the MS results indicate that optimal target surfaces have to be found for individual antioxidants in AP-MALDI-MS but in general smooth surfaces were superior to rough surfaces. Finally the gold-covered stainless steel MALDI target provided the best mass spectra and was selected for all the antioxidants investigated. Copyright © 2009 John Wiley & Sons, Ltd. [source] Electrospray ionization tandem mass spectrometric characteristics of d4T H-phosphonate and distamycin conjugatesRAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 17 2009Jingjing Ding The study of the dissociation of the protonated molecular species [M+H]+ and selected fragment ions allowed proposals for the main fragmentation pathways of the title compounds. The main fragments are formed by expelling a molecule of thymine, thymidine (d4T) or isopropyl. The most striking feature of the tandem mass (MS/MS) spectra is the cleavage of CCO bonds between N -methylpyrrole and carbonyl groups in the presence of the amidine. Electrospray ionization is proven to be a good method for the structural characterization and identification of these kinds of compounds. Copyright © 2009 John Wiley & Sons, Ltd. [source] Electrospray ionization from a gap with adjustable widthRAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 21 2006Patrik Ek In this paper, we present a new concept for electrospray ionization mass spectrometry, where the sample is applied in a gap which is formed between the edges of two triangular-shaped tips. The size of the spray orifice can be changed by varying the gap width. The tips were fabricated from polyethylene terephthalate film with a thickness of 36,µm. To improve the wetting of the gap and sample confinement, the edges of the tips forming the gap were hydrophilized by means of silicon dioxide deposition. Electrospray was performed with gap widths between 1 and 36,µm and flow rates down to 75,nL/min. The gap width could be adjusted in situ during the mass spectrometry experiments and nozzle clogging could be managed by simply widening the gap. Using angiotensin I as analyte, the signal-to-noise ratio increased as the gap width was decreased, and a shift towards higher charge states was observed. The detection limit for angiotensin I was in the low nM range. Copyright © 2006 John Wiley & Sons, Ltd. [source] Electrospray mass spectrometric studies of the complexational behavior of maleonitrile thiacrown ethers with various metalsRAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 5 2006Ines Starke Electrospray ionization was employed to study the mass spectrometric behavior of the maleonitrile tetrathiacrown ethers mn12S4 (1) and mn13S4 (2) and maleonitrile pentathiacrown ether mn15S5 (3) and of their complexes with various metal salts (MX2, M,=,Pd, Pt, Ni, Co, Fe; X,=,Cl, CrCl3, Ni(BF4)2, TlPF6 or Cd(NO3)2) and Cu(SO3CF3)2. Both singly charged, [MXL]+ and [MXL2]+, and doubly charged complexes, [MLn]2+ (n,=,2,5), were observed. The formation of the different complexes consisting of the transition metal ion, the counterion and the various crown ethers and their subsequent dissociation was also studied by collision-induced dissociation measurements which were also used to evaluate the relative stabilities of the complexes. It was found that the collisional voltages for the dissociation of the complexes were generally greater in the [MXL]+ complexes than in the corresponding [MXL2]+ complexes. Copyright © 2006 John Wiley & Sons, Ltd. [source] Can radical cations of the constituents of nucleic acids be formed in the gas phase using ternary transition metal complexes?,RAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 13 2005Sheena Wee Electrospray ionization (ESI) tandem mass spectrometry (MS/MS) of ternary transition metal complexes of [M(L3)(N)]2+ (where M,=,copper(II) or platinum(II); L3,=,diethylenetriamine (dien) or 2,2,:6,,2,-terpyridine (tpy); N,=,the nucleobases: adenine, guanine, thymine and cytosine; the nucleosides: 2,deoxyadenosine, 2,deoxyguanosine, 2,deoxythymine, 2,deoxycytidine; the nucleotides: 2,deoxyadenosine 5,-monophosphate, 2,deoxyguanosine 5,-monophosphate, 2,deoxythymine 5,-monophosphate, 2,deoxycytidine 5,-monophosphate) was examined as a means of forming radical cations of the constituents of nucleic acids in the gas phase. In general, sufficient quantities of the ternary complexes [M(L3)(N)]2+ could be formed for MS/MS studies by subjecting methanolic solutions of mixtures of a metal salt [M(L3)X2] (where M,=,Cu(II) or Pt(II); L3,=,dien or tpy; X,=,Cl or NO3) and N to ESI. The only exceptions were thymine and its derivatives, which failed to form sufficient abundances of [M(L3)(N)]2+ ions when: (a) M,=,Pt(II) and L3,=,dien or tpy; (b) M,=,Cu(II) and L3,=,dien. In some instances higher oligomeric complexes were formed; e.g., [Pt(tpy)(dG)n]2+ (n,=,1,13). Each of the ternary complexes [M(L3)(N)]2+ was mass-selected and then subjected to collision-induced dissociation (CID) in a quadrupole ion trap. The types of fragmentation reactions observed for these complexes depend on the nature of all three components (metal, auxiliary ligand and nucleic acid constituent) and can be classified into: (i) a redox reaction which results in the formation of the radical cation of the nucleic acid constituent, N+.; (ii) loss of the nucleic acid constituent in its protonated form; and (iii) fragmentation of the nucleic acid constituent. Only the copper complexes yielded radical cations of the nucleic acid constituent, with [Cu(tpy)(N)]2+ being the preferred complex due to suppression, in this case, of the loss of the nucleobase in its protonated form. The yields of the radical cations of the nucleobases from the copper complexes follow the order of their ionization potentials (IPs): G (lowest IP),>,A,>,C,>,T (highest IP). Sufficient yields of the radical cations of each of the nucleobases allowed their CID reactions (in MS3 experiments) to be compared to their even-electron counterparts. Copyright © 2005 John Wiley & Sons, Ltd. [source] Electrospray ionization with ambient pressure ion mobility separation and mass analysis by orthogonal time-of-flight mass spectrometryRAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 23 2001Wes E. Steiner Rapid screening and identification of drug and other mixtures are possible using a novel ambient pressure high-resolution ion mobility (APIMS) orthogonal reflector time-of-flight mass spectrometer (TOFMS). Departing ions from the APIMS drift tube traversed a pressure interface between the APIMS and TOFMS where they were subjected to numerous gas collisions that could produce selective fragmentation. By increasing the accelerating field in the pressure interface region, the ions generated using water-cooled electrospray ionization (ESI) underwent collision-induced dissociation (CID). Mixtures of ESI ions were separated by APIMS based on their respective size-to-charge (s/z) ratios while CID and analysis of mass-to-charge (m/z) ratios occurred in the pressure interface and TOFMS. Product ions that were formed in this pressure interface region could be readily assigned to precursor ions by matching the mobility drift times. This process was demonstrated by the examination of a mixture of amphetamines and the resulting fragmentation patterns of the mobility-separated precursor ion species [M,+,H]+. Copyright © 2001 John Wiley & Sons, Ltd. [source] Electrospray ionization using disposable plastic pipette tipsRAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 19 2001Sergei Aksyonov No abstract is available for this article. [source] Genotyping single nucleotide polymorphisms using intact polymerase chain reaction products by electrospray quadrupole mass spectrometryRAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 18 2001James J. Walters Both single nucleotide polymorphisms (SNPs) and mutations are commonly observed in the gene encoding the tumor suppressor protein, p53. SNPs occur at specific locations within genes whereas mutations may be distributed across large regions of genes. When determining nucleotide differences, mass spectrometry is the only method other than Sanger sequencing which offers direct structural information. Electrospray ionization (ESI) quadrupole mass spectrometry (MS) analysis of intact polymerase chain reaction (PCR) products was performed following a simple purification and on-line heating to limit ion adduction. The PCR products were amplified directly from genomic DNA rather than plasmids, as in our previous work. Two known polymorphisms of the p53 gene were genotyped. A cytosine (C) or guanine (G) transversion, designated C,,,G (G,,,C on the opposite strand), were each detected by a 40.0,Da change upon ESI quadrupole MS analysis. Using known PCR products as standards, the genotypes determined for 10 human samples corresponded with restriction fragment length polymorphism (RFLP) analysis. Cytosine/thymine (T) transitions, designated C,,,T (G,,,A on the opposite strand), were also genotyped by ESI-MS. This SNP is discriminated by a 15.0,Da change on one strand (C,,,T) and a 16.0,Da change on the other (G,,,A). Appropriate sample preparation and instrumental configuration (including heated sample inlet syringe and MS source), to limit adducts, are both vital for successful ESI quadrupole MS analysis of intact PCR products. Copyright © 2001 John Wiley & Sons, Ltd. [source] Electrospray ionization in the study of sol-gel processes: the polycondensation of Ti(O-n-Bu)4 in the presence of Si(OEt)4RAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 6 2001Simone Cristoni The polycondensation of Ti(O-n-Bu)4 in presence of Si(OEt)4 (Et,=,C2H5, Bu,=,C4H9) has been studied by electrospray ionization of their mixtures in methanol. Series of oligomers due to Ti(OMe)4 (Me,=,CH3) polycondensation have been detected and represent the most abundant species. This result can be explained by the ready alcoholysis of Ti(O-n-Bu)4 and by its fast kinetics of oligomerization. However a series of Ti,Si-containing oligomers, with molecular weights in the range 400,1300,Da, has also been detected. Their structures have been characterized by isotopic cluster analysis and MS/MS experiments, proving that they originate by reaction of Ti-OH and Si-OEt moieties. Copyright © 2001 John Wiley & Sons, Ltd. [source] Early Structural Evolution of Native Cytochrome c after Solvent RemovalCHEMBIOCHEM, Issue 15 2008Michal Z. Steinberg Abstract Electrospray ionization transfers thermally labile biomolecules, such as proteins, from solution into the gas phase, where they can be studied by mass spectrometry. Covalent bonds are generally preserved during and after the phase transition, but it is less clear to what extent noncovalent interactions are affected by the new gaseous environment. Here, we present atomic-level computational data on the structural rearrangement of native cytochrome c immediately after solvent removal. The first structural changes after desolvation occur surprisingly early, on a timescale of picoseconds. For the time segment of up to 4.2 ns investigated here, we observed no significant breaking of native noncovalent bonds; instead, we found formation of new noncovalent bonds. This generally involves charged residues on the protein surface, resulting in transiently stabilized intermediate structures with a global fold that is essentially the same as that in solution. Comparison with data from native electron capture dissociation experiments corroborates both its mechanistic postulations and our computational predictions, and suggests that global structural changes take place on a millisecond timescale not covered by our simulations. [source] Synthesis of Novel Phosphorylated Daidzein Derivatives and ESI Investigation on Their Non-Covalent Complexes with LysozymeCHINESE JOURNAL OF CHEMISTRY, Issue 7 2007Xiao-Lan Chen Abstract Daidzein (7,4,-dihydroxyisoflavone) was phosphorylated by a modified Atherton-Todd reaction. The structures of the five target product, were determined by X-ray, IR, NMR and ESI-MS. Electrospray ionization results show that in the gas phase all the phosphorylated daidzein derivatives could form non-covalent complexes with the protein lysozyme, while non-covalent complexes were not detected in the mixed solution of daidzein with lysozyme. Relative affinity of every non-covalent complex was obtained according to its different decomposition orifice voltage. [source] Application of liquid chromatography,Tandem mass spectrometry method for the analysis of new nonselective ,-adrenergic blocker 1-(1- H -indol-4-yloxy)-3-{[2-(2-methoxy phenoxy)ethylo]amino}propan-2-ol (2F109) in rat plasmaCHIRALITY, Issue 7 2007Maria Walczak Abstract A sensitive and specific liquid chromatography electrospray ionization,tandem mass spectrometry method for the enantioselective determination of the novel ,-adrenolytic compound, 1-(1- H -indol-4-yloxy)-3-{[2-(2-methoxyphenoxy)ethylo]amino} propan-2-ol, in rat plasma has been developed and validated. Chromatography was performed on a reversed-phase Chiralcel OD-RH analytical column (150 × 4.6 mm, 5 ,m, Daicel Chemical Industries, Tokyo, Japan) with isocratic elution using a mobile phase containing acetonitrile and water with 0.01% formic acid. Detection was achieved by an Applied Biosystems MDS Sciex (Concord, Ontario, Canada) API 2000 triple quadrupole mass spectrometer. Electrospray ionization (ESI) was used for ion production. The limit of detection in the MRM mode was found to be 1.25 ng/ml. The limit of quantification of both enantiomers was 2.5 ng/ml. The precision and accuracy for both intra- and inter-day determination of 2F109 enantiomers ranged from 2.6 to 12% and from 89.1 to 107.1%. This analytical method allowed us to carry out pharmacokinetic studies in rats. Our findings demonstrate that 2F109 shows stereoselective disposition in rat plasma after i.v. administration. The terminal half-lives of (+)-(R)-2F109 and (,)-(S)-2F109 were 33.5 and 42.6 min, respectively. The AUC0,inf of (+)-(R)-2F109 exceeded that of (,)-(S)-2F109. Chirality, 2007. © 2007 Wiley-Liss, Inc. [source] A rapid screening LC-MS/MS method based on conventional HPLC pumps for the analysis of low molecular weight xenobiotics: application to doping control analysisDRUG TESTING AND ANALYSIS, Issue 7 2010Monica Mazzarino Abstract This study presents a fast multi-analyte screening method specifically developed for the detection of xenobiotics in urine. The proposed method allows the screening of several classes of substance in a single chromatographic method with a run-time of 11 min, inclusive of post-run and reconditioning times. Chromatographic separation is achieved in 7.2 min using a reversed-phase 2.7 µm fused-core particle column, generating a back-pressure not exceeding 400 bar and therefore enabling the use of traditional high performance liquid chromatography (HPLC) instruments. The effectiveness of this approach was evaluated, by liquid-chromatography tandem mass spectrometry (LC-MS/MS) in positive electrospray ionization, using 20 blank urine samples spiked with 45 compounds prohibited in sport: 11 diuretics, 16 glucocorticoids, 9 stimulants, 5 anti-oestrogens, as well as formoterol, carboxy-finasteride (previously prohibited by the World Anti-Doping Agency (WADA) in 2008), gestrinone and tetrahydrogestrinone. Qualitative validation shows the proposed method to be specific with no significant interference. All of the analytes considered in this study were clearly distinguishable in urine, with limits of detection ranging from 5 ng/mL to 350 ng/mL, significantly below the Minimum Required Performance Levels (MRPL) set by WADA for the accredited sports anti-doping laboratories. All compounds of interest were separated, including synthetic and endogenous glucocorticoids with similar retention times and fragmentation patterns. Copyright © 2010 John Wiley & Sons, Ltd. [source] Screening for the calstabin-ryanodine receptor complex stabilizers JTV-519 and S-107 in doping control analysisDRUG TESTING AND ANALYSIS, Issue 1 2009Mario Thevis Abstract Recent studies outlined the influence of exercise on the stability of the skeletal muscle calstabin1-ryanodine receptor1-complex, which represents a major Ca2+ release channel. The progressive modification of the type-1 skeletal muscle ryanodine receptor (RyR1) combined with reduced levels of calstabin1 and phosphodiesterase PDE4D3 resulted in a Ca2+ leak that has been a suggested cause of muscle damage and impaired exercise capacity. The use of 1,4-benzothiazepine derivatives such as the drug candidates JTV-519 and S-107 enhanced rebinding of calstabin1 to RyR1 and resulted in significantly improved skeletal muscle function and exercise performance in rodents. Due to the fact that the mechanism of RyR1 remodelling under exercise conditions were proven to be similar in mice and humans, a comparable effect of JTV-519 and S-107 on trained athletes is expected, making the compounds relevant for doping controls. After synthesis of JTV-519, S-107, and a putative desmethylated metabolite of S-107, target compounds were characterized using nuclear magnetic resonance spectroscopy and electrospray ionization (ESI),high-resolution/high-accuracy Orbitrap mass spectrometry. Collision-induced dissociation pathways were suggested based on the determination of elemental compositions of product ions and H/D-exchange experiments. The most diagnostic product ion of JTV-519 was found at m/z 188 (representing the 4-benzyl-1-methyl piperidine residue), and S-107 as well as its desmethylated analog yielded characteristic fragments at m/z 153 and 138 (accounting for 1-methoxy-4-methylsulfanyl-benzene and 4-methoxy-benzenethiol residues, respectively). The analytes were implemented in existing doping control screening procedures based on liquid chromatography, multiple reaction monitoring and simultaneous precursor ion scanning modes using a triple quadrupole mass spectrometer. Validation items such as specificity, recovery (68,92%), lower limit of detection (0.1,0.2 ng/mL), intraday (5.2,18.5%) and interday (8.7,18.8%) precision as well as ion suppression/enhancement effects were determined. Copyright © 2009 John Wiley & Sons, Ltd. [source] Simple method for determination of cocaine and main metabolites in urine by CE coupled to MSELECTROPHORESIS, Issue 12 2009José Luiz da Costa Abstract In this work, a simple method for the simultaneous determination of cocaine (COC) and five COC metabolites (benzoylecgonine, cocaethylene (CET), anhydroecgonine, anhydroecgonine methyl ester and ecgonine methyl ester) in human urine using CE coupled to MS via electrospray ionization (CE-ESI-MS) was developed and validated. Formic acid at 1,mol/L concentration was used as electrolyte whereas formic acid at 0.05,mol/L concentration in 1:1 methanol:water composed the coaxial sheath liquid at the ESI nozzle. The developed method presented good linearity in the dynamic range from 250,ng/mL to 5000,ng/mL (coefficient of determination greater than 0.98 for all compounds). LODs (signal-to-noise ratio of 3) were 100,ng/mL for COC and CET and 250,ng/mL for the other studied metabolites whereas LOQ's (signal-to-noise ratio of 10) were 250,ng/mL for COC and CET and 500,ng/mL for all other compounds. Intra-day precision and recovery tests estimated at three different concentration levels (500, 1500 and 5000,ng/mL) provided RSD lower than 10% (except anhydroecgonine, 18% RSD) and recoveries from 83,109% for all analytes. The method was successfully applied to real cases. For the positive urine samples, the presence of COC and its metabolites was further confirmed by MS/MS experiments. [source] Cyclodextrin-based nonaqueous electrokinetic chromatography with UV and mass spectrometric detection: Application to the impurity profiling of amiodarone,ELECTROPHORESIS, Issue 17 2008Roelof Mol Abstract The potential of nonaqueous electrokinetic chromatography (NAEKC) using cyclodextrins (CD) for the analysis of basic drugs and related compounds was evaluated. Both UV absorbance and mass spectrometric (MS) detection were employed. Addition of neutral CD to the NA background electrolyte did not significantly enhance the separation of a test mixture of basic drugs, and no change in selectivity was observed. In contrast, anionic single-isomer-sulfated CD strongly added to the selectivity of the NAEKC system inducing an improved resolution among the test compounds and increasing the migration time window. The applicability of the NAEKC system using anionic CD is demonstrated by the profiling of a sample of the drug amiodarone that had been stored for 1,year at room temperature. Amiodarone is poorly soluble in water. NAEKC-UV analysis indicated the presence of at least seven impurities in the amiodarone sample. In order to identify these compounds, the NAEKC system was coupled directly to electrospray ionization (ESI) ion-trap MS. The total of detected impurities increased to 12 due to the added sensitivity and selectivity of MS detection. Based on the acquired MS/MS data, three sample constituents could be identified as ,known' impurities (British Pharmacopoeia), whereas for three unknown impurities molecular structures could be proposed. Estimated limits of detection for amiodarone using the NAEKC method were 1,,g/mL with UV detection and 15,ng/mL with ESI-MS detection (full-scan). Based on relative responses, the impurity content of the stored drug substance was estimated to be 0.33 and 0.47% using NAEKC-UV and NAEKC-ESI-MS, respectively. [source] Urtica dioica agglutinin: Separation, identification, and quantitation of individual isolectins by capillary electrophoresis and capillary electrophoresis,mass spectrometryELECTROPHORESIS, Issue 9 2005Markus Ganzera Abstract With benign prostatic hyperplasia (BPH) being a major health problem in ageing men, alternative therapeutic approaches (e.g., with phytopharmaceuticals) are of great interest. Based on pharmacological evidences, one of the most promising options in that respect are the lectins found in Urtica dioica (stinging nettle) roots. In this study the qualitative and quantitative analysis of individual isolectins in U. dioica extracts is described, which is the first report on using capillary electrophoresis (CE) for the analysis of lectins in plant material at all. By utilizing a 200 mM sodium acetate buffer (pH 3.75) a baseline separation and determination of four closely related isolectins was feasible within 20 min in the aqueous plant extracts. The individual compounds were identified based on reference compounds as well as data obtained from CE-mass spectrometry (MS) experiments. After modifying the optimized CE conditions to 100 mM ammonium formate buffer with pH 3.75 and a voltage of 15 kV, the isolectins were clearly assignable in positive electrospray ionization (ESI) mode. The quantitative results obtained by CE (the total lectin content varied from 0 to 0.42% in the samples) were accurate (recovery rates of spiked samples between 92.5 and 96.2%), precise (relative standard deviation < 5%) and in good agreement to those obtained by High-performance liquid chromatography (HPLC). As for peak resolution, assignable compounds and required separation time the newly developed CE method was clearly advantageous over the determination achieved by LC. [source] Identification of diphenhydramine metabolites in human urine by capillary electrophoresis-ion trap-mass spectrometryELECTROPHORESIS, Issue 10-11 2004Andrea Baldacci Abstract The identification of diphenhydramine (DH) metabolites that are frequently observed in the capillary zone electrophoresis (CZE) and micellar electrokinetic capillary chromatography (MEKC) analyses of alkaline liquid/liquid and solid-phase extracts of patient urines is demonstrated. Having standards for DH and diphenhydramine- N -oxide (DHNO), the presence of these two compounds could be confirmed in urines that were collected overnight after administration of 25 mg DH chloride. Using CZE coupled to ion-trap mass spectrometry (CE-MSn) with positive electrospray ionization and an acetate buffer at pH 5.6, the [M+H]+ ions of DH (m/z = 256), DHNO (m/z = 272), and nordiphenhydramine (NDH, m/z = 242) and their fragmentation to a common m/z 167 product ion (diphenylcarbinol moiety) was monitored. The data indicate that all three compounds are cations in an acidic environment, the migration order being NDH, DH, and DHNO. Data obtained under negative electrospray ionization conditions suggest the presence of diphenylmethoxyacetic acid-glycine amide ([M-H], ion of m/z 298 and fragmentation to m/z 254, loss of CO2), a metabolite that could tentatively be assigned to a characteristic peak observed in the MEKC electropherogram at alkaline pH. The data presented in this paper illustrate the value of using CE-MSn for identification of urinary drug metabolites for which no standards are available. [source] Occurrence of pharmaceuticals and hormones in sewage sludgeENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 7 2010Antonio Nieto Abstract The present study evaluates the presence of nine hormones and their conjugates and 20 pharmaceuticals such as anti-inflammatories, lipid regulators, and antibiotics among others in sewage sludge from two sewage treatment plants (STPs) in the Tarragona area (Spain) for the period March 2007 until March 2008. Target analytes have been determined using different methods involving pressurized liquid extraction and liquid chromatography (electrospray ionization) tandem mass spectrometry (MS-MS). Most of the pharmaceuticals and hormones were found at low micrograms per kilogram dry weight levels in the sewage sludge samples analyzed. Some compounds were present in all samples, such as acetaminophen, caffeine, carbamazepine, and ibuprofen, among others. Other compounds, such as estriol, were found only in the STP of Reus. The compounds that showed the highest concentration in both STPs were roxithromycin and tylosin (1,446 and 1,958,µg/kg dry wt, respectively). The presence of these compounds in sewage sludge demonstrated that they are partially or totally removed from the influent wastewater by sorption into the sewage sludge. Environ. Toxicol. Chem. 2010;29:1484,1489. © 2010 SETAC [source] Photodegradation of common environmental pharmaceuticals and estrogens in river waterENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 6 2005Angela Yu-Chen Lin Abstract Photodegradation rates of five pharmaceuticals (gemfibrozil, ibuprofen, ketoprofen, naproxen, and propranolol) and of four estrogens (estriol, estrone [E1], 17,-estradiol [E2], and 17,-ethinylestradiol [EE2]), which are common contaminants in the aquatic environment, were measured in both purified and river water at environmentally relevant concentrations (1,2 ,g/L) and different oxygen concentrations. Solutions were irradiated with a xenon arc lamp (765 W/m2; 290 nm < , < 700 nm) and analyzed using a high-performance liquid chromatography-tandem mass spectrometry method with electrospray ionization for pharmaceuticals and atmospheric pressure photoionization for estrogens. In river water, half-lives were 4.1 h for ketoprofen, 1.1 min for propranolol, 1.4 h for naproxen, 2 to 3 h for estrogens, and 15 h for gemfibrozil and ibuprofen. In air-saturated purified water, rates generally were slower except for that of ketoprofen, which reacted with a half-life of 2.5 min. Naproxen, propranolol, and E1 reacted with half-lives of 1.9, 4.4, and 4.7 h, respectively. The EE2, estriol, E2, gemfibrozil, and ibuprofen reacted with half-lives of 28.4, 38.2, 41.7, 91.4, and 205 h, respectively. The presence of oxygen doubled the direct photolysis rates of naproxen and propranolol. In nonautoclaved river water, 80% of E2 rapidly biotransformed to E1 within less than 20 min, whereas all other compounds remained stable over 22 h. [source] Gas-Phase Chemistry of Vanadium Oxide Cluster Cations VmOn+ (m = 1,4; n = 1,10) with Water and Molecular OxygenEUROPEAN JOURNAL OF INORGANIC CHEMISTRY, Issue 31 2008Sandra Feyel Abstract Bare vanadium oxide cluster cations VmOn+ (m = 1,4; n =1,10) generated by electrospray ionization are investigated with respect to their reactivity toward water and molecular oxygen by using mass spectrometric techniques. Besides ion hydration, the ion/molecule reactions of VmOn+ with oxygen-labeled water (H218O) also lead to 16O/18O exchange reactions of the vanadium oxide clusters cations. Although the probability of degenerate 16O/18O exchange between VmOn+ and water is fairly high for the cluster cations with a medium valence state of vanadium, oxygen-atom exchange reactions between VmOn+ and 18O2 can only be accomplished by VO+, V3O6+, and V4O8+. Particularly interesting is the fact that not only oxygen atoms from vanadyl units are exchanged in the cluster cations, but bridging oxygen atoms are also most likely involved in the processes. Other reaction channels for the interaction of VmOn+ cluster cations with molecular oxygen are reported as well, such as oxidative degradation of the low-valent cluster cations upon collision with O2 and formation of association complexes for the high-valent cluster cations. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008) [source] Fragmentation of the (Cyclam-acetato)iron Azide Cation in the Gas PhaseEUROPEAN JOURNAL OF INORGANIC CHEMISTRY, Issue 6 2007Detlef Schröder Abstract Mass spectrometry is used to investigate the fragmentation of the ligated azidoiron cation [(cyclam-acetato)Fe(N3)]+, which is accessible in the gas phase by electrospray ionization of a solution of its hexafluorophosphate salt in methanol/water. Upon collisional activation, mass-selected [(cyclam-acetato)Fe(N3)]+ undergoes competing loss of dinitrogen or HN3 as the prevailing fragmentations. The former dissociation pathway is investigated in detail in order to determine whether or not the free, high-valent iron nitride [(cyclam-acetato)FeN]+ is formed. The evidence obtained indeed supports the formation of the iron nitride species as an intermediate, although the long-lived ion sampled after mass selection may also have undergone further rearrangements.(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007) [source] Peptides of human gingival crevicular fluid determined by HPLC-ESI-MSEUROPEAN JOURNAL OF ORAL SCIENCES, Issue 6 2005Elisabetta Pisano The acidic-soluble protein content of human gingival crevicular fluid was analyzed by reverse-phase high-performance liquid chromatography (RP-HPLC), and the eluent deriving from the chromatography separation was directly introduced into an ion-trap mass spectrometer through electrospray ionization (ESI-IT MS). By this technique the molecular weight of peptides/proteins was determined with a precision of ,,1/10,000 amu. On the basis of the chromatographic behavior and the knowledge of the molecular mass value, some peptides and proteins soluble in acidic solution were unambiguously recognized. Besides high quantities of human serum albumin, , -defensins 1,4 and minor amounts of cystatin A, statherin, basic PB salivary peptide and other unidentified components were detected. The presence of , -defensins in gingival crevicular fluid is in agreement with their relevant contribution to protein composition deriving from granulocyte secretions. Other peptides and proteins abundant in human saliva, such as proline-rich proteins (PRPs) and histatins, were not detected in gingival crevicular fluid. Further investigations will be necessary to establish the origin of statherin and PB salivary peptide in gingival crevicular fluid. [source] Hydrogen/deuterium exchange kinetics of cytochrome C: An electrospray ionization fast flow experimentISRAEL JOURNAL OF CHEMISTRY, Issue 3-4 2003Orit Geller New experiments are described in which the gas phase hydrogen/deuterium (H/D) exchange kinetics is studied for multiply-protonated cytochrome c ions with +10 to +17 charges. The experimental technique involves electrospray ionization (ESI) combined with a fast-flow method. Experimental results are presented including (1) average rate constants for H/D exchange, (2) overall decay kinetics of the reactant ion, and (3) sets of profiles for consecutive deuterium exchanges as a function of the flow rate of ND3 as the deuterating agent. The maximum number of exchanged hydrogen atoms and the exchange rate are observed to increase with increasing charge. The +13 state demonstrates special reactivity with a reactant ion decay constant of 2.5 × 10,9 cc/molecule's. Further insight into the H/D exchange mechanism is anticipated upon analysis of the data with a newly developed algorithm for extracting site-specific rate constants from profiles for H/D exchange in gas phase protonated amino acids, their clusters, and peptides. The algorithm minimizes the mutual entropy or the Kullback-Leibler information divergence between the observed concentrations and a chosen model. [source] | ||||||||||||||||||||||||||||