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M/z
Kinds of M/z Terms modified by M/z Selected AbstractsProstate carcinoma tissue proteomics for biomarker discoveryCANCER, Issue 12 2003Yaxin Zheng M.D. Abstract BACKGROUND The advent of the prostate-specific antigen (PSA) test has had a profound impact on the diagnosis and treatment of prostate carcinoma. However, the use of PSA levels alone for screening for prostate carcinoma was compromised by the variations in the amount of PSA produced by the benign prostatic tissue specimens. Proteins were involved in various pathways that determine the behavior of a cell. Therefore, information regarding proteins may reveal drug targets and/or markers for early detection. METHODS The authors used surface-enhanced laser desorption/ionization time-of-flight mass spectrometry to determine the protein profiles from fresh tissues of the prostate. Laser capture microdissection was performed to isolate pure populations of cells. RESULTS The authors identified a protein with an average m/Z of 24,782.56 ± 107.27 that was correlated with the presence of prostate carcinoma. Furthermore, using laser capture microdissection, they demonstrated that the origin of this protein, which the authors designated PCa-24, was derived from the epithelial cells of the prostate. PCa-24 expression was detected in 16 of 17 (94%) prostate carcinoma specimens but not in paired normal cells. In addition, this protein was not expressed in any of the 12 benign prostatic hyperplasia specimens that were assayed. CONCLUSIONS PCa-24 may be useful a marker for prostate carcinoma. Cancer 2003;98:2576,82. © 2003 American Cancer Society. [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] An automated, sheathless capillary electrophoresis-mass spectrometry platform for discovery of biomarkers in human serumELECTROPHORESIS, Issue 7-8 2005Alexander P. Sassi Abstract A capillary electrophoresis-mass spectrometry (CE-MS) method has been developed to perform routine, automated analysis of low-molecular-weight peptides in human serum. The method incorporates transient isotachophoresis for in-line preconcentration and a sheathless electrospray interface. To evaluate the performance of the method and demonstrate the utility of the approach, an experiment was designed in which peptides were added to sera from individuals at each of two different concentrations, artificially creating two groups of samples. The CE-MS data from the serum samples were divided into separate training and test sets. A pattern-recognition/feature-selection algorithm based on support vector machines was used to select the mass-to-charge (m/z) values from the training set data that distinguished the two groups of samples from each other. The added peptides were identified correctly as the distinguishing features, and pattern recognition based on these peptides was used to assign each sample in the independent test set to its respective group. A twofold difference in peptide concentration could be detected with statistical significance (p -value < 0.0001). The accuracy of the assignment was 95%, demonstrating the utility of this technique for the discovery of patterns of biomarkers in serum. [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] Anatoxin-a toxin in the cyanobacterium Planktothrix rubescens from a fishing pond in northern ItalyENVIRONMENTAL TOXICOLOGY, Issue 3 2004Emanuela Viaggiu Abstract A heavy algal bloom occurring in a fishing pond in northern Italy full of Salmo trutta was examined for algae taxonomy and toxic production. The dominant algal species (98%) was identified as the cyanobacterium Planktothrix rubescens (D.C. ex GOMONT) Komarek Anagnostidis, based on morphological examination, and it was revealed to be toxic in mouse and Vibrio fischeri bioassays. The toxin was identified as anatoxin-a using high-performance liquid chromatography and confirmed using liquid chromatography,mass spectrometry (LC-MS). The mouse bioassay gave signs of poisoning, as previously reported for anatoxin-a. The LC-MS confirmed the presence of an anatoxin-a peak at m/z 166 (M+H+). The content of toxin in the field population was estimated at 12.13 ,g/g of fresh cells. The bloom was sustained by the very high N/P ratio in the water. This is the first report in Italy of an anatoxin-a-producing Planktothrix rubescens population. © 2004 Wiley Periodicals, Inc. Environ Toxicol 19: 191,197, 2004. [source] Reduction of [(C5Me5)2Mo2O5] and [(C5Me5)2Mo2O4] in Methanol/Water/Trifluoroacetate Solutions Investigated by Combined On-Line Electrochemistry/Electrospray-Ionization Mass SpectrometryEUROPEAN JOURNAL OF INORGANIC CHEMISTRY, Issue 12 2003Jenny Gun Abstract Complexes [Cp*2Mo2O5] (Cp* = ,5 -C5Me5) and [Cp*2Mo2O4] were investigated by combined on-line electrochemical (EC) reduction and electrospray-ionization mass spectrometry (ESI-MS) techniques in a trifluoroacetic acid buffered water/methanol solution. The reduction products at the larger negative potentials are identical for both compounds. The studies reveal the existence of a wide range of previously unknown di- and trinuclear MoV, MoIV, MoIII, and mixed-valence complexes that were identified on the basis of their masses and characteristic isotope patterns. The structures of the initial compounds and the product of electroreduction with m/z = 713,729 were supported by in situ MSn experiments that allowed the elucidation of the fragmentation pathway for the collision-induced dissociation. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003) [source] Comparative analysis of triacylglycerols from Olea europaea L. fruits using HPLC and MALDI-TOFMSEUROPEAN JOURNAL OF LIPID SCIENCE AND TECHNOLOGY, Issue 5 2010Faouzi Sakouhi Abstract MALDI-TOFMS and HPLC are two analytical methods that were used to characterize triacylglycerols (TAG) of the Meski, Sayali, and Picholine Tunisian olive varieties. The HPLC chromatograms of the oils showed the presence of 15 TAG species, among which triolein (OOO) was the most abundant (21,48%). In the Sayali cultivar, OOO was the predominant TAG species followed by POO and LOO. However, the minor TAG molecules were represented by LnLO and LnLP. MALDI mass spectra produced sodiated ([M,+,Na]+) and potassiated ([M,+,K]+) TAG molecules; only the major TAG were potassiated [OOO,+,K] ([OOO,+,K]+, [POO,+,K]+, and [LOO,+,K]+). In contrast to the HPLC chromatograms, the MALDI mass spectra showed 13 peaks of TAG. The major peak was detected at m/z,907, which corresponds to OOO with an Na+ adduct. The results from both HPLC and MALDI techniques predict the fatty acid composition and their percentages for each olive variety. Practical applications: TAG are the main components in vegetable oils. These biomolecules determine the physical, chemical, and nutritional properties of the oils. The nutritional benefits of TAG are related to DAG (moderate plasma lipid level) and esterified FA, which are intermediate biosynthetic molecules of TAG. TAG analysis is necessary to discriminate between oils of different origin, since some oils have similar FA profiles. Olive products, oils, and table olives, are the main diet sources of TAG in the Mediterranean countries. In this work, chromatographic and spectrometric methods were used for TAG analysis and characterization of Tunisian olive varieties. [source] Brain angiotensin-converting enzymes: role of angiotensin-converting enzyme 2 in processing angiotensin II in miceEXPERIMENTAL PHYSIOLOGY, Issue 5 2008Khalid M. Elased Angiotensin (Ang)-converting enzyme 2 (ACE2) metabolizes Ang II to the vasodilatory peptide Ang(1,7), while neprilysin (NEP) generates Ang(1,7) from Ang I. Experiments used novel Surface Enhanced Laser Desorption Ionization-Time of Flight (SELDI-TOF) mass spectroscopic (MS) assays to study Ang processing. Mass spectroscopy was used to measure proteolytic conversion of Ang peptide substrates to their specific peptide products. We compared ACE/ACE2 activity in plasma, brain and kidney from C57BL/6 and NEP,/, mice. Plasma or tissue extracts were incubated with Ang I or Ang II (1296 or 1045, m/z, respectively), and generated peptides were monitored with MS. Angiotensin-converting enzyme 2 activity was detected in kidney and brain, but not in plasma. Brain ACE2 activity was highest in hypothalamus. Angiotensin-converting enzyme 2 activity was inhibited by the specific ACE2 inhibitor, DX600 (10 ,m, 99% inhibition), but not by the ACE inhibitor, captopril (10 ,m). Both MS and colorimetric assays showed high ACE activity in plasma and kidney with low levels in brain. To extend these findings, ACE measurements were made in ACE overexpressing mice. Angiotensin-converting enzyme four-copy mice showed higher ACE activity in kidney and plasma with low levels in hypothalamus. In hypothalamus from NEP,/, mice, generation of Ang(1,7) from Ang I was decreased, suggesting a role for NEP in Ang metabolism. With Ang II as substrate, there was no difference between NEP,/, and wild-type control mice, indicating that other enzymes may contribute to generation of Ang(1,7). The data suggest a predominant role of hypothalamic ACE2 in the processing of Ang II, in contrast to ACE, which is most active in plasma. [source] Deamidation of labile asparagine residues in the autoregulatory sequence of human phenylalanine hydroxylaseFEBS JOURNAL, Issue 5 2003Structural, functional implications Two dimensional electrophoresis has revealed a microheterogeneity in the recombinant human phenylalanine hydroxylase (hPAH) protomer, that is the result of spontaneous nonenzymatic deamidations of labile asparagine (Asn) residues [Solstad, T. and Flatmark, T. (2000) Eur. J. Biochem.267, 6302,6310]. Using of a computer algorithm, the relative deamidation rates of all Asn residues in hPAH have been predicted, and we here verify that Asn32, followed by a glycine residue, as well as Asn28 and Asn30 in a loop region of the N-terminal autoregulatory sequence (residues 19,33) of wt-hPAH, are among the susceptible residues. First, on MALDI-TOF mass spectrometry of the 24 h expressed enzyme, the E. coli 28-residue peptide, L15,K42 (containing three Asn residues), was recovered with four monoisotopic mass numbers (i.e., m/z of 3106.455, 3107.470, 3108.474 and 3109.476, of decreasing intensity) that differed by 1 Da. Secondly, by reverse-phase chromatography, isoaspartyl (isoAsp) was demonstrated in this 28-residue peptide by its methylation by protein- l -isoaspartic acid O -methyltransferase (PIMT; EC 2.1.1.77). Thirdly, on incubation at pH 7.0 and 37 °C of the phosphorylated form (at Ser16) of this 28-residue peptide, a time-dependent mobility shift from tR,,34 min to ,,31 min (i.e., to a more hydrophilic position) was observed on reverse-phase chromatography, and the recovery of the tR,,34 min species decreased with a biphasic time-course with t0.5 -values of 1.9 and 6.2 days. The fastest rate is compatible with the rate determined for the sequence-controlled deamidation of Asn32 (in a pentapeptide without 3D structural interference), i.e., a deamidation half-time of ,,1.5 days in 150 mm Tris/HCl, pH 7.0 at 37 °C. Asn32 is located in a cluster of three Asn residues (Asn28, Asn30 and Asn32) of a loop structure stabilized by a hydrogen-bond network. Deamidation of Asn32 introduces a negative charge and a partial ,-isomerization (isoAsp), which is predicted to result in a change in the backbone conformation of the loop structure and a repositioning of the autoregulatory sequence and thus affect its regulatory properties. The functional implications of this deamidation was further studied by site-directed mutagenesis, and the mutant form (Asn32,Asp) revealed a 1.7-fold increase in the catalytic efficiency, an increased affinity and positive cooperativity of L-Phe binding as well as substrate inhibition. [source] Three pheromone-binding proteins in olfactory sensilla of the two silkmoth species Antheraea polyphemus and Antheraea pernyiFEBS JOURNAL, Issue 10 2000Rosario Maida Females of the sibling silkmoth species Antheraea polyphemus and A. pernyi use the same three sex pheromone components in different ratios to attract conspecific males. Accordingly, the sensory hairs on the antennae of males contain three receptor cells sensitive to each of the pheromone components. In agreement with the number of pheromones used, three different pheromone-binding proteins (PBPs) could be identified in pheromone-sensitive hairs of both species by combining biochemical and molecular cloning techniques. MALDI-TOF MS of sensillum lymph droplets from pheromone-sensitive sensilla trichodea of male A. polyphemus revealed the presence of three major peaks with m/z of 15702, 15752 and 15780 and two minor peaks of m/z 15963 and 15983. In Western blots with four antisera raised against different silkmoth odorant-binding proteins, immunoreactivity was found only with an anti-(Apol PBP) serum. Free-flow IEF, ion-exchange chromatography and Western blot analyses revealed at least three anti-(Apol PBP) immunoreactive proteins with pI values between 4.4 and 4.7. N-Terminal sequencing of these three proteins revealed two proteins (Apol PBP1a and Apol PBP1b) identical in the first 49 amino acids to the already known PBP (Apol PBP1) [Raming, K., Krieger, J. & Breer, H. (1989) FEBS Lett.256, 2215,2218] and a new PBP having only 57% identity with this amino-acid region. Screening of antennal cDNA libraries with an oligonucleotide probe corresponding to the N-terminal end of the new A. polyphemus PBP, led to the discovery of full length clones encoding this protein in A. polyphemus (Apol PBP3) and in A. pernyi (Aper PBP3). By screening the antennal cDNA library of A. polyphemus with a digoxigenin-labelled A. pernyi PBP2 cDNA [Krieger, J., Raming, K. & Breer, H. (1991) Biochim. Biophys. Acta1088, 277,284] a homologous PBP (Apol PBP2) was cloned. Binding studies with the two main pheromone components of A. polyphemus and A. pernyi, the (E,Z)-6,11-hexadecadienyl acetate (AC1) and the (E,Z)-6,11-hexadecadienal (ALD), revealed that in A. polyphemus both Apol PBP1a and the new Apol PBP3 bound the 3H-labelled acetate, whereas no binding of the 3H-labelled aldehyde was found. In A. pernyi two PBPs from sensory hair homogenates showed binding affinity for the AC1 (Aper PBP1) and the ALD (Aper PBP2), respectively. [source] Mechanism of metabolic activation and DNA adduct formation by the human carcinogen diethylstilbestrol: The defining link to natural estrogensINTERNATIONAL JOURNAL OF CANCER, Issue 6 2009Muhammad Saeed Abstract Diethylstilbestrol (DES) is a human carcinogen, based on sufficient epidemiological evidence. DES is mainly metabolized to its catechol, 3,-hydroxyDES (3,-OH-DES), which can further oxidize to DES-3,,4,-quinone (DES-3,,4,-Q). Similarly to estradiol-3,4-quinone, the reaction of DES-3,,4,-Q with DNA would form the depurinating 3,-OH-DES-6,-N3Ade and 3,-OH-DES-6,-N7Gua adducts. To prove this hypothesis, synthesis of DES-3,,4,-Q by oxidation of 3,-OH-DES with Ag2O was tried; this failed due to instantaneous formation of a spiro -quinone. Oxidation of 3,-OH-DES by lactoperoxidase or tyrosinase in the presence of DNA led to the formation of 3,-OH-DES-6,-N3Ade and 3,-OH-DES-6,-N7Gua adducts. These adducts were tentatively identified by LC-MS/MS as 3,-OH-DES-6,-N3Ade, m/z = 418 [M+H]+, and 3,-OH-DES-6,-N7Gua, m/z = 434 [M+H]+. Demonstration of their structures derived from their oxidation by MnO2 to the DES quinone adducts and subsequent tautomerization to the dienestrol (DIES) catechol adducts, which are identical to the standard 3,-OH-DIES-6,-N3Ade, m/z = 416 [M+H]+, and 3,-OH-DIES-6,-N7Gua, m/z = 432 [M+H]+, adducts. The reaction of DIES-3,,4,-Q or lactoperoxidase-activated 3,-OH-DIES with DNA did not produce any depurinating adducts, due to the dienic chain being perpendicular to the phenyl planes, which impedes the intercalation of DIES into the DNA. Enzymic oxidation of 3,-OH-DES suggests that the catechol of DES intercalates into DNA and is then oxidized to its quinone to yield N3Ade and N7Gua adducts. These results suggest that the common denominator of tumor initiation by the synthetic estrogen DES and the natural estrogen estradiol is formation of their catechol quinones, which react with DNA to afford the depurinating N3Ade and N7Gua adducts. © 2008 Wiley-Liss, Inc. [source] Metabolism of the mesoionic compound (MI-D) by mouse liver microsome, detection of its metabolite In Vivo, and acute toxicity in miceJOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY, Issue 6 2009Silvia Romão Abstract The mesoionic derivative 4-phenyl-5-[4-nitrocinnamoyl]-1,3,4-thiadiazolyl-2-phenylamine chloride (MI-D) has antitumoral and anti-inflammatory effects. In this study, we present aspects of its metabolism and toxicity in mice. MI-D was metabolized in vitro by liver microsome, generating a main product with a much shorter retention time than MI-D in high-performance liquid chromatography (HPLC) analysis but with a spectrum similar to that of the original molecule. Mass spectrometry with electrospray ionization in positive mode analysis of the purified compound by HPLC indicated that the product of metabolism has four additional hydroxyl groups (m/z = 465) compared with MI-D (m/z = 401). The HPLC analyses of plasma and urine samples from mice treated with MI-D showed the presence of the metabolite product. The kinetic parameters Km (19.5 ± 4.5 ,M) and Vmax [1.5 ± 0.4 units of fluorescence/(100 ,g of microsomal protein/mL/s)] were estimated, confirming the metabolism of MI-D and indicating that the reaction follows Michaelis-Menten kinetics. Acute toxicity was established on the basis of an estimation of mean lethal dose (LD-50; 181.2 mg/kg) and histopathological analysis of animals that survived the LD-50 test. Abdominal adhesions, inflammatory foci, and formation of granulomas were observed. Altogether, the results contribute to the advancement of research in support of MI-D as a future chemotherapeutic drug. © 2009 Wiley Periodicals, Inc. J Biochem Mol Toxicol 23:394,405, 2009; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.20303 [source] Determination of glycyrrhetic acid in human plasma by HPLC-MS method and investigation of its pharmacokineticsJOURNAL OF CLINICAL PHARMACY & THERAPEUTICS, Issue 3 2008W.-J. Zhao PhD Summary Objective:, To develop a high performance liquid chromatography mass spectrometry (HPLC-MS) method for the determination of the glycyrrhetic acid (GA) in human plasma and for the investigation of its pharmacokinetics after the oral administration of 150 mg diammonium glycyrrhizinate test and reference capsule formulations. Methods:, The GA in plasma was extracted with ethyl acetate, separated on a C18 column with a mobile phase of methanol (5 mmol/L ammonium acetate),water (85 : 15, V/V) and analysed using a MS detector. Ursolic acid (UA) was used as internal standard. The target ions were m/z 469·5 for GA and m/z 455·6 for UA, the fragment voltages were 200 V and 100 V for GA and UA respectively. Results:, The calibration curve was linear over the range of 0·5,200 ng/mL (r = 0·9974). The limit of quantification for GA in plasma was 0·5 ng/mL, the recovery was 76·0,80·0%, and the inter- and intra-day relative standard deviations (RSD) were <12%. The pharmacokinetic parameters of GA after a single dose of 150 mg diammonium glycyrrhizinate test and reference were as follows: the half life (t1/2) 9·65 ± 3·54 h and 9·46 ± 2·85 h, the time to peak concentration (Tmax) 10·95 ± 1·32 h and 11·00 ± 1·30 h, the peak concentration (Cmax) 95·57 ± 43·06 ng/mL and 103·89 ± 49·24 ng/mL; the area under time-concentration curve (AUC0,48 and AUC0,,) 1281·84 ± 527·11 ng·h/mL and 1367·74 ± 563·27 ng·h/mL, 1314·32 ± 566·40 ng·h/mL and 1396·97 ± 630·06 ng·h/mL. The relative bioavailability of diammonium glycyrrhizinate capsule was 98·88 ± 12·98%. Conclusion:, The assay was sensitive, accurate and convenient, and can be used for the determination of GA in human plasma. Comparison of the bioavailability and pharmacokinetic profile of GA indicated that the test and reference capsules were bioequivalent. [source] Synthesis and isolation of chloro-,-carbolines obtained by chlorination of ,-carboline alkaloids in solution and in solid stateJOURNAL OF HETEROCYCLIC CHEMISTRY, Issue 3 2003Maria A. Ponce ,-Carbolines (1-5) undergo electrophilic aromatic substitution with N -chlorosuccinimide and N -chlorobenzotriazole under different experimental conditions. Although 6-chloro and 8-chloro-nor-har-mane (1a and 1b) and 6-chloro and 8-chloro-harmane (2a and 2b) obtained by chlorination with sodium hypochlorite of nor-harmane (1) and harmane (2) were isolated and fully characterized recently, other chloroderivatives of nor-harmane and harmane have never been described. The preparation and subsequent isolation, purification and full characterization of the dichloroderivatives 1c and 2c are reported (mp, Rf, 1H nmr, 13C nmr and ms) together with the preparation, isolation and charaterization, for the first time, of the chloroderivatives obtained from harmine (3a-3c), harmol (4a-4b) and 7-acetylharmol (5a-5c). As chlorinating reagent N -chlorosuccinimide and N -chlorobenzotriazole in solution as well as the ,-carboline - N -chlorosuccinimide solid mixture have been used and their uses have been compared. Gc (tR) and gc-ms (m/z) data for other monochloro derivative of nor-harmane (1d) and monochloro- and dichloroderivatives of harmane (2d and 2e-2f), obtained in trace amounts, are also included (Scheme 1 and Table I). Semiempirical AM1 and PM3 calculations have been performed in order to predict reactivity in terms of the energies of HOMO-LUMO difference and in terms of the charge density of ,-carbolines (1-5) and chloro-,-carbolines (1a-1c, 2a-2c, 3a-3c, 4a-4b, and 5a-5c) (Scheme 1). Theoretical and experimental results are discussed briefly. [source] The evolution of volatile compounds profile of "Toscano" dry-cured ham during ripening as revealed by SPME-GC-MS approach,JOURNAL OF MASS SPECTROMETRY (INCORP BIOLOGICAL MASS SPECTROMETRY), Issue 9 2010C. Pugliese Abstract The volatile compounds profile is an important feature for the characterization of dry-cured hams. Some minor typical Italian products, such as ,Toscano' ham, have been poorly studied in regards to their composition of volatile compounds. In this article, we studied the evolution of the aromatic profile of ,Toscano' dry-cured ham by solid-phase microextraction-gas chromatographic-mass spectrometry (SPME-GC-MS) with ripening. Ten right thighs were cured according to the ,Toscano' PDO protocol, sampled at 0, 1, 3, 6 and 12 months and submitted to volatile compounds analysis by SPME with a Divinylbenzene (DVB)/Carboxen/Polydimethylsiloxane (PDMS) 75-µ Stable Flex fibre. An Agilent 5975C mass selective detector (MSD) spectrometer with electron ionization (EI) source operating in scan mode within the m/z 29,350 range was used for data collection. Seven internal standards, either deuterium labeled or absent in the specimens and chosen to represent low or high boiling esters, alcohols, acids or phenols, were added to the homogenized samples and used to normalize the SPME fibre response to account for response changes upon wearing. Linear calibrations were obtained in this way for selected representative compounds. Over 60 compounds belonging to esters, aldehydes, organic acids, ketones and alcohols were identified by comparison with spectral libraries and Kovats indices. Aldehydes were the most represented chemical family, followed by organic acids, alcohols, ketones and esters. The aldehydes and ketones increased during the first 3 months, when the larger formation of volatiles occurred. For other families, the evolution over time was less evident. The principal component and discriminant analyses of the aromatic profile were effective in classifying the hams at 0, 6 or 12 months of ripening while for 1 and 3 months' samples a partial overlapping was shown. These results represent the first characterization of ,Toscano' ham and may constitute the basis to identify the best ripening time and define an analytical quality standard for this typical ham. Copyright © 2010 John Wiley & Sons, Ltd. [source] Animal urine as painting materials in African rock art revealed by cluster ToF-SIMS mass spectrometry imagingJOURNAL OF MASS SPECTROMETRY (INCORP BIOLOGICAL MASS SPECTROMETRY), Issue 8 2010Vincent Mazel Abstract The rock art site at the village of Songo in Mali is a very important Dogon ritual place where, since the end of the nineteenth century until today, takes place the ceremony of circumcision. During these ceremonies, paintings are performed on the walls of the shelter with mainly three colors: red, black and white. Ethnological literature mentions the use of animal urine of different species such as birds, lizards or snakes as a white pigment. Urine of these animals is mainly composed of uric acid or urate salts. In this article, time-of-flight secondary ion mass spectrometry (ToF-SIMS) is used to compare uric acid, snake urine and a sample of a white pigment of a Dogon painting coming from the rock art site of Songo. ToF-SIMS measurements in both positive and negative ion modes on reference compounds and snake urine proved useful for the study of uric acid and urate salts. This method enables to identify unambiguously these compounds owing to the detection in negative ion mode of the ion corresponding to the deprotonated molecule ([M , H], at m/z 167.01) and its fragment ions. Moreover, the mass spectra obtained in positive ion mode permit to differentiate uric acid and urate salts on the basis of specific ions. Applying this method to the Dogon white pigments sample, we show that the sample is entirely composed of uric acid. This proves for the first time, that animal urine was used as a pigment by the Dogon. The presence of uric acid instead of urate salts as normally expected in animal urine could be explained by the preparation of the pigment for its application on the stone. Copyright © 2010 John Wiley & Sons, Ltd. [source] Matrix-assisted laser desorption/ionization tissue profiling of secretoneurin in the nucleus accumbens shell from cocaine-sensitized ratsJOURNAL OF MASS SPECTROMETRY (INCORP BIOLOGICAL MASS SPECTROMETRY), Issue 1 2010Joachim D. Uys Abstract Proteins in the nucleus accumbens mediate many cocaine-induced behaviors. In an effort to measure changes in nucleus accumbens protein expression as potential biomarkers for addiction, coronal tissue sections were obtained from rats that developed behavioral sensitization after daily administration of cocaine, or from daily saline-treated controls. The tissue sections were subjected to matrix-assisted laser desorption/ionization (MALDI) mass spectrometry (MS) profiling and tissue imaging. For profiling experiments, brain sections were manually spotted with matrix over the nucleus accumbens, a brain region known to regulate cocaine sensitization. Summed mass spectra (10 000 laser shots, grid) were acquired and spectra were aligned to reference peaks. Using bioinformatics tools, eight spectral features were found to be altered by cocaine treatment. Based on additional sequencing experiments with MALDI tandem MS and database searches of measured masses, secretoneurin (m/z 3653) was identified as having an increased expression. In addition, the distribution of m/z 3653 in the nucleus accumbens was determined by MALDI tissue imaging, and the increased expression of its precursor protein, secretogranin II, was verified by immunoblotting. Copyright © 2009 John Wiley & Sons, Ltd. [source] A further investigation on a MALDI-based method for evaluation of markers of renal damageJOURNAL OF MASS SPECTROMETRY (INCORP BIOLOGICAL MASS SPECTROMETRY), Issue 12 2009Annunziata Lapolla Abstract The validity of the urinary protein profile to characterize the pathological states of diabetic, nephropathic and diabetic,nephropathic patients was considered on the basis of previously obtained results by MALDI/MS, showing a different abundance ratio of the collagen ,1 and ,5 chain precursor fragments at m/z 1219 and 2049 and of the uromodulin precursor fragment at m/z 1912 observed in healthy subjects and patients; a larger number of subjects was examined and the obtained results were statistically evaluated. The p values related to the observed differences indicate that they are statistically significant when comparing all patients versus healthy controls, diabetic with normo or microalbuminuria versus nephropathic with advanced renal disease patients and diabetic with normo or microalbuminuria versus diabetic with advanced nephropathy patients. The scatter plot matrix gives evidence of the strict inverse relationship between the abundances of ions at m/z 1912 and 1219, the correlation coefficient being particularly high (r = 0.921, p < 0.001). The relationship between the true positive rate (sensitivity) and false positive rate (1,specificity) for every possible cutoff value in abundance of the considered ionic species was investigated through the receiver-operating characteristic (ROC) curve. The obtained data indicate that a good differentiation of nephropathic patients with advanced renal disease and diabetic patients with advanced nephropathy versus healthy subjects can be easily obtained by this approach. Copyright © 2009 John Wiley & Sons, Ltd. [source] Analysis of intracellular short organic acid-coenzyme A esters from actinomycetes using liquid chromatography-electrospray ionization-mass spectrometryJOURNAL OF MASS SPECTROMETRY (INCORP BIOLOGICAL MASS SPECTROMETRY), Issue 9 2007Je Won Park Abstract A method employing silicone oil density centrifugation, solid-phase extraction (SPE) cleanup, and LC-ESI-MS/MS analysis was developed for the rapid, selective, sensitive, and quantitative detection of an intracellular pool of short organic acid-CoA esters in actinomycetes. The detection limit was determined to be approximately 0.8 pmol (1.2 ng/ml) for each standard CoA-ester analyzed by the present LC-ESI-MS/MS method. A selected ion chromatogram for a typical fragment ion (m/z 428) specific to CoA-esters enabled the detection of eight intracellular CoA-esters involved in both primary and secondary metabolisms. The application of this method to bacterial metabolomic study is demonstrated by the profiling of the intracellular CoA-ester pools in the wild-type Streptomyces venezuelae strain producing polyketide antibiotics (methymycin and pikromycin), a polyketide synthase (PKS)-deleted S. venezuelae mutant, and a S. venezuelae mutant expressing the heterologous PKS genes. By quantifying the individual CoA-esterlevel in three different genotypes of the S. venezuela e strain, further insight could be gained into the role of CoA-estersin polyketide biosynthesis. This analytical approach can be extended to the quantification of the size and composition of in vivo CoA-ester pools in various microbes, and can provide a detailed understanding of the relationship between the in vivo CoA-ester pool and the production of pharmaceutically important polyketides. Copyright © 2007 John Wiley & Sons, Ltd. [source] Fiber introduction mass spectrometry: determination of pesticides in herbal infusions using a novel sol,gel PDMS/PVA fiber for solid-phase microextractionJOURNAL OF MASS SPECTROMETRY (INCORP BIOLOGICAL MASS SPECTROMETRY), Issue 6 2007Rogério Cesar da Silva Abstract An application of the direct coupling of solid-phase microextraction (SPME) with mass spectrometry (MS), a technique known as fiber introduction mass spectrometry (FIMS), is described to determine organochlorine (OCP) and organophosphorus (OPP) pesticides in herbal infusions of Passiflora L. A new fiber coated with a composite of poly(dimethylsiloxane) and poly(vinyl alcohol) (PDMS/PVA) was used. Sensitive, selective, simple and simultaneous quantification of several OCP and OPP was achieved by monitoring diagnostic fragment ions of m/z 266 (chlorothalonil), m/z 195 (,-endosulfan), m/z 278 (fenthion), m/z 263 (methyl parathion) and m/z 173 (malathion). Simple headspace SPME extraction (25 min) and fast FIMS detection (less than 40 s) of OCP and OPP from a highly complex herbal matrix provided good linearity with correlation coefficients of 0.991,0.999 for concentrations ranging from 10 to 140 ng ml,1 of each compound. Good accuracy (80 to 110%), precision (0.6,14.9%) and low limits of detection (0.3,3.9 ng ml,1) were also obtained. Even after 400 desorption cycles inside the ionization source of the mass spectrometer, no visible degradation of the novel PDMS/PVA fiber was detected, confirming its suitability for FIMS. Fast (ca 20 s) pesticide desorption occurs for the PDMS/PVA fiber owing to the small thickness of the film and its reduced water sorption. Copyright © 2007 John Wiley & Sons, Ltd. [source] In situ diagnostics of the decomposition of silacyclobutane on a hot filament by vacuum ultraviolet laser ionization mass spectrometryJOURNAL OF MASS SPECTROMETRY (INCORP BIOLOGICAL MASS SPECTROMETRY), Issue 5 2007Y. J. Shi Abstract The gas-phase reaction products of silacyclobutane (SCB) and 1, 1-dideuterio-silacyclobutane (SCB- d2) from a hot-wire chemical vapor deposition (HWCVD) chamber were diagnosed in situ using vacuum ultraviolet (VUV) laser single-photon ionization (SPI) coupled with time-of-flight (TOF) mass spectrometry. The SCB molecule was found to decompose at a filament temperature as low as 900 °C. Both Si- (silylene, methylsilylene, and silene) and C-containing (ethene and propene) species were produced from the SCB decomposition on the filament. Ethene and propene were detected by the mass spectrometer. It is demonstrated that the formation of ethene is favored over that of propene. The experimental study of hot-wire decomposition of SCB- d2 shows that propene is most likely produced by a process that is initiated by a 1,2-H(D) migration to form n -propylsilylene, followed by an equilibration with silacyclopropane, which then decomposes to propene. The detection of ethene in our experiment indicates that a competitive route of fragmentation exists for SCB decomposition on the filament. It has been shown that this competitive route occurs without H/D scrambling. The highly reactive silylene, silene, and methylsilylene species produced from SCB decomposition underwent either insertion reactions into the SiH bonds of the parent molecule or ,-type addition reaction across the double and triple CC bonds. The dimerization product of silene, 1,3-disilacyclobutane, at m/z = 88 was also observed. Copyright © 2007 John Wiley & Sons, Ltd. [source] Coprecipitation with calcium hydroxide for determination of iron in fish otoliths by collision cell ICP-MS,JOURNAL OF MASS SPECTROMETRY (INCORP BIOLOGICAL MASS SPECTROMETRY), Issue 5 2007Stephanie L. Daniels Abstract A method has been described for the determination of iron from fish otoliths containing high levels of calcium by collision cell technology (CCT) ICP-MS. Iron (Fe) in otolith solutions was quantitatively coprecipitated with small amounts of calcium hydroxide by adding 1.0 M sodium hydroxide solution. The performance of CCT-ICP-MS pressurized with He/H2 cell gas was investigated on the elimination of Ca-based spectral interferences at m/z 54, 56 and 57. Molecular ion interferences at m/z 54 and 56 were reduced by 2 orders of magnitude. However, the interferences at m/z 57 increased by the same amount in the presence of Ca in solutions owing to the formation of 40Ca16 OH+ through reactions with H2 in collision cell, indicating that 57Fe was not suitable for the determination of Fe from otoliths. Results for 56Fe suffered significantly from interferences of Ca-based molecular ions when the Ca concentration in solution exceeded 100 µg ml,1, for which matrix-matched calibration was required for accurate determination. CCT with the aid of He/H2 cell gas proved to be very effective in eliminating the interferences (40Ar14N+ and 40Ca14N+) at m/z 54. Presence of Ca up to 300 µg ml,1 had virtually no effect on the ion signals of 54Fe, which with low background signals, afforded accurate determination of Fe from otoliths by using aqueous external standards. Copyright © 2007 John Wiley & Sons, Ltd. [source] A rapid and sensitive liquid chromatography/positive ion tandem mass spectrometry method for the determination of cimetropium in human plasma by liquid,liquid extractionJOURNAL OF MASS SPECTROMETRY (INCORP BIOLOGICAL MASS SPECTROMETRY), Issue 7 2006Heon-Woo Lee Abstract We have developed and validated a simple detection system with high-performance liquid chromatography (HPLC) with positive ion electrospray ionization tandem mass spectrometry (ESI-MS/MS) for determining cimetropium levels in human plasma using scopolamine butyl bromide as an internal standard (I.S.). The acquisition was performed in the multiple reaction monitoring (MRM) mode, by monitoring the transitions: m/z 357.9 > 103.1 for cimetropium and m/z 359.9 > 103.1 for butyl-scopolamine. The method involves a simple single-step liquid,liquid extraction with dichloromethane. The analyte was chromatographed on an YMC C18 reversed-phase chromatographic column by isocratic elution with 10 mM ammonium formate buffer,methanol (19 : 81, v/v; adjusted to pH 4.0 with formic acid). The results were linear over the studied range (0.2,100 ng ml,1), with r2 = 1.0000, and the total analysis time for each run was 2 min. Intra- and interassay precisions were 0.70,8.54% and 1.08,4.85%, respectively, and intra- and interassay accuracies were 97.56,108.23% and 97.48,103.91%, respectively. The lower limit of quantification (LLOQ) was 0.2 ng ml,1. At this concentration, mean intra- and interassay precisions were 8.54% and 4.85%, respectively, and mean intra- and interassay accuracies were 97.56% and 98.91%, respectively. The mean recovery ranged from 62.71 ± 4.06 to 64.23 ± 2.32%. Cimetropium was found to be stable in plasma samples under typical storage and processing conditions. The devised assay was successfully applied to a pharmacokinetic study of cimetropium bromide administered as a single oral dose (150 mg) to healthy volunteers. Copyright © 2006 John Wiley & Sons, Ltd. [source] Site-specific detection of S -nitrosylated PKB ,/Akt1 from rat soleus muscle using CapLC-Q-TOFmicro mass spectrometryJOURNAL OF MASS SPECTROMETRY (INCORP BIOLOGICAL MASS SPECTROMETRY), Issue 9 2005Xiao-Ming Lu Abstract Protein Kinase B,(PKB,, or Akt1) is believed to play a crucial role in programmed cell death, cancer progression and the insulin-signaling cascade. The protein is activated by phosphorylation at multiple sites and subsequently phosphorylates and activates eNOS. Free cysteine residues of the protein may capture reactive, endogenously produced nitric oxide (NO) as S -nitrosothiols. Site-specific detection of S -nitrosylated cysteine residues, usually at low stoichiometry, has been a major challenge in proteomic research largely due to the lack of mass marker for S -nitrosothiols that are very labile under physiologic conditions. In this report we describe a sensitive and specific MS method for detection of S -nitrosothiols in PKB ,/Akt1 in rat soleus muscle. PKB ,/Akt1 was isolated by immunoprecipitation and 2D-gel electrophoresis, subjected to in-gel tryptic digestion, and cysteinyl nitrosothiols were reacted with iodoacetic acids [2-C12/C13 = 50/50] under ascorbate reduction conditions. This resulted in the production of relatively stable carboxymethylcysteine (CMC) immonium ions (m/z 134.019 and m/z 135.019) within a narrow argon collision energy (CE = 30 ± 5 V) in the high MS noise region. In addition, free and disulfide-linked cysteine residues were converted to carboxyamidomethylcysteines (CAM). Tryptic S -nitrosylated parent ion was detected with a mass accuracy of 50 mDa for the two CMC immonium ions at the triggered elution time during capillary liquid chromatography (LC) separation. A peptide containing Cys296 was discriminated from four co-eluting tryptic peptides under lock mass conditions (m/z 785.8426). S -nitrosothiol in the tryptic peptide, ITDFGLBKEGIK (B: CAM, [M + 2H]2+ = 690.86, Found: 690.83), is believed to be present at a very low level, since the threshold for the CMC immonium trigger ions was set at 3 counts/s in the MS survey. The high levels of NO that are produced under stress conditions may result in increased S -nitrosylation of Cys296 which blocks disulfide bond formation between Cys296 and Cys310 and suppresses the biological effects of PKB ,/Akt1. With the procedures developed here, this process can be studied under physiological and pathological conditions. Copyright © 2005 John Wiley & Sons, Ltd. [source] A validated liquid chromatographic/tandem mass spectrometric method for the determination of phencyclidine in microliter samples of rat serumJOURNAL OF MASS SPECTROMETRY (INCORP BIOLOGICAL MASS SPECTROMETRY), Issue 1 2005Howard P. Hendrickson Abstract A liquid chromatographic/tandem mass spectrometric method is described for the determination of phencyclidine (PCP) in small volumes of rat serum (e.g. 50 µl). Samples were extracted using a mixed-mode strong cation-exchange column and then separated isocratically using a narrow-bore (2.1 mm i.d.) 3 µm Hypersil phenyl column and a mobile phase consisting of an ammonium formate buffer (pH 2.7) with 60% (v/v) methanol. Detection was accomplished using positive ion electrospray ionization in the multiple reaction monitoring mode. Mass spectra were obtained and peaks were observed at an m/z (% abundance) of 244 (100), 159 (25), and 86 (89). Tandem mass spectra were also obtained from the m/z 244 precursor ion with peaks observed at m/z 159 (100), 86 (96), and 91 (11). Optimum serum PCP sensitivity and precision were obtained at a transition of m/z 244 , 159. Matrix-associated ion suppression did not significantly affect the accuracy (100,112%) or precision (CV ,8%) of the assay. The lower limit of quantitation was 1 ng ml,1 in 50 µl of serum. The method was used to study the serum pharmacokinetics of PCP in rats after an intravenous bolus dose of PCP. Copyright © 2004 John Wiley & Sons, Ltd. [source] Mass spectrometric analysis of 7-sulfoxymethyl-12-methylbenz[a]anthracene and related electrophilic polycyclic aromatic hydrocarbon metabolitesJOURNAL OF MASS SPECTROMETRY (INCORP BIOLOGICAL MASS SPECTROMETRY), Issue 11 2004Andreas F. Lehner Abstract The Meso-region theory of polycyclic aromatic hydrocarbon (PAH) carcinogenesis predicts that the development of pronounced carcinogenicity depends on the introduction of a good leaving group on alkyl side-chains attached to the exceptionally reactive meso-anthracenic or L-region positions of PAHs. Thus, the first step in carcinogenesis by methylated PAHs such as 7,12-dimethylbenz[a]anthracene (DMBA) would be the hydroxylation of the L-region methyl groups, particularly the 7-methyl group. The second would be the formation of a metabolite, e.g. a sulfate ester, which is expected to be a good leaving group capable of generating a highly reactive benzylic carbocation. 7-Hydroxymethyl-12-methylbenz[a]anthracene (7-HMBA) is a metabolite of DMBA, and sulfation of 7-HMBA to a 7-sulfoxymethyl metabolite (7-SMBA) is a known Phase II metabolic process designed to facilitate excretion, but actually enabling more destructive side-reactions. These side-reactions occur with generation of an electrophilic 7-methylene carbonium ion, and/or by in vivo halide exchange to provide neutral side-products more capable of entering cells, especially those of DMBA target tissues. Electrospray ionization mass spectrometry (MS) enabled us to visualize 7-SMBA as an intact m/z 351 conjugate anion by negative mode, and as a released m/z 255 carbonium ion by positive mode. Upon prolonged refrigeration, 7-SMBA accumulated an m/z 383 photooxide, which appeared capable of re-evolving the starting material as visualized by tandem quadrupole MS, or MS/MS. The 7-SMBA carbonium ion provided interpretable fragments when studied by fragment ion MS/MS, including those representing the loss of up to several protons. Subtle differences in this property were encountered upon perturbing 7-SMBA, either by warming it at 37 °C for 2 h or by substituting the initial sulfoxy group with an iodo group. Side-reactions accounting for such proton losses are proposed, and are of interest whether they occur in the mass spectrometer, in solution or both; these proposals include acidity at the 12-methyl position and cyclization between the 12-methyl group and the adjacent C-1 position. It is also suggested that such side-reactions may comprise one route to relieving steric strain arising between the 12-methyl group and the angular benzo ring of 7-SMBA. Copyright © 2004 John Wiley & Sons, Ltd. [source] Simple, sensitive and rapid liquid chromatographic/electrospray ionization tandem mass spectrometric method for the quantification of lacidipine in human plasmaJOURNAL OF MASS SPECTROMETRY (INCORP BIOLOGICAL MASS SPECTROMETRY), Issue 7 2004N. V. S. Ramakrishna Abstract A simple, sensitive and rapid liquid chromatographic/electrospray ionization tandem mass spectrometric method was developed and validated for the quantification of lacidipine in human plasma using its structural analogue, amlodipine, as internal standard (IS). The method involves a simple single-step liquid,liquid extraction with tert -butyl methyl ether. The analyte was chromatographed on an Xterra MS C18 reversed-phase chromatographic column by isocratic elution with 20 mM ammonium acetate buffer,acetonitrile (10 : 90, v/v; pH 6) and analyzed by mass spectrometry in the multiple reaction monitoring mode. The precursor to product ion transitions of m/z 456.4 , 354.4 and m/z 409.3 , 238.3 were used to measure the analyte and the I.S., respectively. The chromatographic run time was 1.5 min and the weighted (1/x2) calibration curves were linear over the range 0.1,25 ng ml,1. Lacidipine was sensitive to temperature in addition to light. The method was validated in terms of accuracy, precision, absolute recovery, freeze,thaw stability, bench-top stability and re-injection reproducibility. The limit of detection and lower limit of quantification in human plasma were 50 and 100 pg ml,1, respectively. The within- and between-batch accuracy and precision were found to be well within acceptable limits (<15%). The analyte was stable after three freeze,thaw cycles (deviation <15%). The average absolute recoveries of lacidipine and amlodipine (IS) from spiked plasma samples were 51.1 ± 1.3 and 50.3 ± 4.9%, respectively. The assay method described here could be applied to study the pharmacokinetics of lacidipine. Copyright © 2004 John Wiley & Sons, Ltd. [source] Peak capacity of ion mobility mass spectrometry: the utility of varying drift gas polarizability for the separation of tryptic peptidesJOURNAL OF MASS SPECTROMETRY (INCORP BIOLOGICAL MASS SPECTROMETRY), Issue 4 2004Brandon T. Ruotolo Abstract Ion mobility mass spectrometry (IM-MS) peptide mass mapping experiments were performed using a variety of drift gases (He, N2, Ar and CH4). The drift gases studied cover a range of polarizabilities ((0.2,2.6) × 10,24 cm3) and the peak capacities obtained for tryptic peptides in each gas are compared. Although the different gases exhibit similar peak capacities (5430 (Ar) to 7580 (N2)) in some cases separation selectivity presumably based on peptide conformers (or conformer populations), is observed. For example the drift time profiles observed for some tryptic peptide ions from aldolase (rabbit muscle) show a dependence on drift gas. The transmission of high-mass ions (m/z > 2000) is also influenced by increased scattering cross-section of the more massive drift gases. Consequently the practical peak capacity for IM-MS separation cannot be assumed to be solely a function of resolution and the ability of a gas to distribute signals in two-dimensional space; rather, peak capacity estimates must account for the transmission losses experienced for peptide ions as the drift gas mass increases. Copyright © 2004 John Wiley & Sons, Ltd. [source] Characterization of ,- and ,-glutamyl dipeptides by negative ion collision-induced dissociationJOURNAL OF MASS SPECTROMETRY (INCORP BIOLOGICAL MASS SPECTROMETRY), Issue 2 2004Alex G. Harrison Abstract The low-energy CID mass spectra of the [M , H], ions of a variety of dipeptides containing glutamic acid have been obtained using cone-voltage collisional activation. Dipeptides with the ,-linkage, H-Glu(Xxx-OH)-OH, are readily distinguished from those with the ,-linkage, H-Glu-Xxx-OH, by the much more prominent elimination of H-Xxx-OH from the [M , H], ions of the former isomers, resulting in formation of m/z 128, presumably deprotonated pyroglutamic acid. Dipeptides with the reverse linkage, H-Xxx-Glu-OH, show distinctive fragmentation reactions of the [M , H], ions including enhanced elimination of CO2 and formation of deprotonated glutamic acid. Exchange of the labile hydrogens for deuterium has shown that there is considerable interchange of C-bonded hydrogens with labile (N- and O-bonded) hydrogens prior to most fragmentation reactions. All dipeptides show loss of H2O from [M , H],. MS3 studies show that the [M , H , H2O], ion derived from H-Glu-Gly-OH has the structure of deprotonated pyroglutamylglycine while the [M , H , H2O], ions derived from H-Glu(Gly-OH)-OH and H-Gly-Glu-OH show a different fragmentation behaviour indicating distinct structures for the fragment ions. Copyright © 2004 John Wiley & Sons, Ltd. [source] Unusual atmospheric pressure chemical ionization conditions for detection of organic peroxidesJOURNAL OF MASS SPECTROMETRY (INCORP BIOLOGICAL MASS SPECTROMETRY), Issue 9 2003David Rondeau Abstract Organic peroxides such as the cumene hydroperoxide I (Mr = 152 u), the di- tert -butyl peroxide II (Mr = 146 u) and the tert -butyl peroxybenzoate III (Mr = 194 u) were analyzed by atmospheric pressure chemical ionization mass spectrometry using a water,methanol mixture as solvent with a low flow-rate of mobile phase and unusual conditions of the source temperature (,50 °C) and probe temperature (70,200 °C). The mass spectra of these compounds show the formation of (i) an [M + H]+ ion (m/z 153) for the hydroperoxide I, (ii) a stable adduct [M + CH3OH2]+ ion (m/z 179) for the dialkyl peroxide II and (iii) several protonated adduct species such as protonated molecules (m/z 195) and different protonated adduct ions (m/z 227, 389 and 421) for the peroxyester III. Tandem mass spectrometric experiments, exact mass measurements and theoretical calculations were performed for characterize these gas-phase ionic species. Using the double-well energy potential model illustrating a gas-phase bimolecular reaction, three important factors are taken into account to propose a qualitative interpretation of peroxide behavior toward the CH3OH2+, i.e. thermochemical parameters () and two kinetic factors such as the capture constant of the initial stable ion,dipole and the magnitude of the rate constant of proton transfer reaction into the loose proton bond cluster. Copyright © 2003 John Wiley & Sons, Ltd. 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