bluuebunny/crossref_metadata_2025 huggingface dataset:
Probing reactive sites for ion‐molecule reactions of anthraquinones with dimethyl ether using an external source ion trap tandem mass spectrometer and computational chemistry
Authors: Wu Hui‐Fen , Chen Li‐Wei , Chen Chien‐Hung
Published: January 2005

Gas‐phase ion‐molecule reactions of anthraquinone derivatives with dimethyl ether (DME) were investigated using an external source ion trap mass spectrometer. Semi‐empirical calculations were executed to determine possible reactive sites for the product ions. Collision activated dissociation (CAD) was successfully performed for very low abundance of ion‐molecule products. Even for product ions with a relative intensity below 1%, CAD experiments can be successfully performed. Significantly more structural information could be elucidated based on this special feature. Importantly, the CAD spectra of very minor ions could be measured by this ion trap instrument, which significantly enhances the future role of the ion trap as a powerful analytical instrument. CAD of all product ions on anthraquinone compounds typically eliminates neutral molecules such as CO or H2O. A hydration phenomenon in the CAD processes resulting from the precursor ions incorporating one molecule of H2O and then eliminating one molecule of CO was observed in this study. Copyright © 2001 John Wiley & Sons, Ltd.
Size exclusion chromatography/mass spectrometry applied to the analysis of polysaccharides
Authors: Deery Michael J. , Stimson Elaine , Chappell Colin G.
Published: January 2005

A novel method for analysing polysaccharide materials is described which employs size‐exclusion chromatography (SEC) followed by detection by on‐line electrospray ionisation mass spectrometry (ESI‐MS) and off‐line matrix‐assisted laser desorption/ionisation time‐of‐flight mass spectrometry (MALDI‐TOFMS). It is demonstrated through SEC/ESI ion trap mass spectrometry that the formation of multiply charged oligomer ions, which bind up to five sodium cations, allows the rapid analysis of polysaccharide ions with molecular weights in excess of 9 kDa. MALDI spectra generated from fractionation of the effluent collected from the same SEC separation are shown to be in good agreement with the ESI spectra with respect to molecular weight distributions and types of ions generated. ESI and MALDI mass spectra of samples obtained from sequential graded ethanol precipitation and SEC fractionation of acid and enzymatically digested arabinoxylan polysaccharides show important structural differences between polysaccharide fragments. In addition, a comparison is made between the mass spectra of native and permethylated SEC‐separated fragments of acid and enzymatically treated arabinogalactan. Linkage information of the permethylated arabinogalactan oligomers can be rapidly established through the use of on‐line SEC/ESI‐MS
n experiments. Copyright © 2001 John Wiley & Sons, Ltd.
Determination of cyclic polyester oligomers by gel permeation chromatography and matrix‐assisted laser desorption/ionization time‐of‐flight mass spectrometry
Authors: Laine Olli , Österholm Heidi , Seläntaus Maaria , Järvinen Hannele , Vainiotalo Pirjo
Published: January 2005

Polyesters prepared from adipic acid (AA), phthalic anhydride (PA), isophthalic acid (IPA), terephthalic acid (TPA), and 2‐butyl‐2‐ethyl‐1,3‐propanediol (BEPD) were investigated by gel permeation chromatography (GPC) and matrix‐assisted laser desorption/ionization time‐of‐flight mass spectrometry(MALDI‐TOFMS). All polyesters were found to contain a fraction of low molecular weight molecules that were identified as cyclic ester oligomers. The most abundant cyclic oligomer varied with the diacid used in the synthesis but, in every case, it was either a dimer or a trimer. In addition, the relative amounts of the polyester starting materials influenced the amount of cyclic oligomers formed in the polyesterification reaction. Copyright © 2001 John Wiley & Sons, Ltd.
Rearrangement of P‐N to P‐O bonds in mass spectra of N‐diisopropyloxyphosphoryl amino acids/alcohols
Authors: Chen Jing , Chen Yi , Jiang Yang , Fu Hua , Xin Bin , Zhao Yu‐Fen
Published: January 2005

The cationized N‐diisopropyloxyphosphoryl amino acids/alcohols were analyzed by electrospray ionization tandem mass spectrometry. A rearrangement reaction leading to the P‐N to P‐O bond migration was observed, and cationized phosphoric acid isopropyl ester (PAIE) was formed. The rearrangement did not depend on the chain length of the amino acids/alcohols. A possible rearrangement mechanism was proposed. It was shown that the phosphoryl group has a strong affinity to the hydroxyl group in the gas phase. Copyright © 2001 John Wiley & Sons, Ltd.
Multiphoton dissociation/ionisation of dimethyl sulfide
Authors: Vatsa R. K. , Majumder C. , Jayakumar O. D. , Sharma P. , Kulshreshtha S. K. , Mittal J. P.
Published: January 2005

Multiphoton dissociation/ionisation studies have been carried out at 355 nm for dimethyl disulfide (CH3SSCH3) using a time‐of‐flight‐mass spectrometer. The prominent ion signals observed are CH3+, S+, HCS+ and S2+. No evidence for the formation of a parent ion signal was observed. The laser power variation experiments show a two‐photon dependence for the most prominent HCS+ ion. The presence of a signal at m/e 30 is explained in terms of concerted elimination of ethane from the excited neutral CH3SSCH3 via a cyclic transition state. It is inferred that the multiphoton dissociation of CH3SSCH3 at 355 nm involves both S‐S and C‐S bond cleavage. Based on these results, it has been suggested that CH3S+ isomerises to CH2SH+, which undergoes unimolecular decay to produce HCS+ by H2 elimination. The results have been interpreted in terms of the dissociation of the parent molecule using two photons, followed by the ionisation of the fragments. Copyright © 2001 John Wiley & Sons, Ltd.
The elemental analyzer sample carousel: loading an autosampler made easy
Authors: Wooller Matthew , Collins Bert , Fogel Marilyn
Published: January 2005

A newly developed device for loading samples into an autosampler attached to an elemental analyzer is described and evaluated. The purpose of the device is to reduce the time and number of errors experienced when loading samples into an autosampler. Tests show that the new device saves time when loading samples and, more importantly, reduces the chance of losing samples. In addition to analyzing the elemental components (e.g. % carbon and % nitrogen) and the elemental ratios (e.g. C/N) of a sample, the stable isotopic composition (e.g. δ13C and δ15N) can also be determined when an EA is attached to a stable isotope ratio mass spectrometer. Copyright © 2001 John Wiley & Sons, Ltd.
Impact desolvation of electrosprayed microdroplets – a new ionization method for mass spectrometry of large biomolecules
Authors: Aksyonov Sergei A. , Williams Peter
Published: January 2005

Impact desolvation of electrosprayed microdroplets (IDEM) is a new method for producing gas‐phase ions of large biomolecules. Analytes are dissolved in an electrolyte solution which is electrosprayed in vacuum, producing highly charged micron and sub‐micron sized droplets (microdroplets). These microdroplets are accelerated through potential differences ∼5 − 10 kV to velocities of several km/s and allowed to impact a target surface. The energetic impacts vaporize the droplets and release desolvated gas‐phase ions of the analyte molecules. Oligonucleotides (2‐ to 12‐mer) and peptides (bradykinin, neurotensin) yield singly and doubly charged molecular ions with no detectable fragmentation. Because the extent of multiple charging is significantly less than in atmospheric pressure electrospray ionization, and the method produces ions largely free of adducts from solutions of high ionic strength, IDEM has some promise as a method for coupling to liquid chromatographic techniques and for mixture analysis. Ions are produced in vacuum at a flat equipotential surface, potentially allowing efficient ion extraction. Copyright © 2001 John Wiley & Sons, Ltd.
Secondary ion mass spectrometric investigation of Au‐based composites
Authors: Barison Simona , Piccirillo Clara , Fabrizio Monica , Daolio Sergio
Published: January 2005

The electrodeposition of thick gold layers plays an important role both in traditional and high‐tech productions, such as jewelry and microelectronics, respectively. In this work a secondary ion mass spectrometric study will be presented on Au co‐deposits with (sub‐)micrometric ceramic powders, in order to harden gold. Mass spectra are used to identify the components deposited, providing evidence of the additives and/or eventual contaminants introduced during electrolysis. Furthermore, analysis of ion depth profiles and the intensity distribution of ionic species along the film were studied. Copyright © 2001 John Wiley & Sons, Ltd.
Deceleration of high‐energy matrix‐assisted laser desorption/ionization ions in an open cell for Fourier transform ion cyclotron resonance mass spectrometry
Authors: Frankevich Vladimir , Zenobi Renato
Published: January 2005

A new method of ion deceleration in a Fourier transform ion cyclotron resonance (FTICR) open cell is described that improves the performance of FTICR‐MS instruments equipped with an internal source for laser desorption/ionization. Ion deceleration occurs in the front trapping cylinder of an open cylindrical cell. Decelerating voltages up to 100 V can be applied for 10–500 µs to the front cylinder during ion introduction. The deceleration field is uniformly distributed along the cylinder length giving a ‘smooth’ deceleration, which means that the deceleration is effective over a large time interval and a large m/z range. This results in improved trapping efficiency of high‐energy ions. We demonstrate efficient trapping of high (m/z 66 kDa) mass ions and the possibility to reduce the width of the kinetic energy distribution of MALDI ions with this arrangement. Copyright © 2001 John Wiley & Sons, Ltd.
Quantitative determination of medroxyprogesterone acetate in plasma by liquid chromatography/electrospray ion trap mass spectrometry
Authors: Kim Seong‐Mo , Kim Dong‐Hyun
Published: January 2005

A sensitive and rapid liquid chromatography/electrospray ion trap mass spectrometry (LC/MS/MS) method has been developed for the quantitative determination of medroxyprogesterone acetate (MPA) in human plasma. Plasma samples (1.0 mL) were simply extracted with pentane and the extracts were analyzed by HPLC with the detection of the analyte in the selective reaction monitoring (SRM) mode. The determination of MPA was accurate and reproducible, with a limit of quantitation of 0.05 ng/mL in plasma. The standard calibration curve for MPA was linear (r = 0.998) over the concentration range 0.05–6.0 ng/mL in human plasma. Analysis precision over the concentration range of MPA was lower than 18.8% (relative standard deviation, RSD) and accuracy was between 96.2 and 108.7%. Copyright © 2001 John Wiley & Sons, Ltd.
Drug screening of pharmaceutical discovery compounds by micro‐size exclusion chromatography/mass spectrometry
Authors: Wabnitz Paul A. , Loo Joseph A.
Published: January 2005

Micro‐size exclusion chromatography coupled with capillary liquid chromatography (capLC) and mass spectrometry (MS) provides a rapid and simple approach to the preliminary screening of active ligands toward a specific target macromolecule. In this study, the effectiveness of this technique is demonstrated by a number of small molecule ligands with known binding affinities towards the protein target. All ligands were incubated together with a target protein under native conditions. Separation was then achieved by microcentrifugation where the high molecular weight (MW) compounds were selectively passed through the size‐exclusion material. The retained low MW compounds were then recovered and analyzed by capLC/MS. The absence of the ligand indicated strong affinity towards the target, while ligand detection indicated inactivity. This assay demonstrated the drugs that were acting as strong inhibitors of Co‐PDF from those showing to be comparatively inactive. The relative binding rank order of the drugs towards Co‐PDF was also determined. The results were validated by a corresponding set of control experiments in which the target molecules were excluded from the process. In principle, high‐throughput micro‐size exclusion chromatography, coupled with capLC/MS, offers a powerful technique as a preliminary screen in determining both the strong binding affinity and the relative affinity rank ordering of ligands towards a specific target macromolecule, and is complementary with other analytical drug screening techniques. Copyright © 2001 John Wiley & Sons, Ltd.
Kinetics and isotope patterns of ethanol and acetaldehyde emissions from yeast fermentations of glucose and glucose‐6,6‐d2 using selected ion flow tube mass spectrometry: a case study
Authors: Smith David , Wang Tianshu , S̆paněl Patrik
Published: January 2005

As a prelude to investigations of the emission of metabolites from human cell lines in vitro, we have conducted a study using selected ion flow tube mass spectrometry (SIFT‐MS) of the acetaldehyde and ethanol that appear in the headspace above a fermenting yeast/glucose/water mixture in sealed glass bottles at a temperature of 30 °C. A fixed quantity of yeast (10 mg) and varying amounts (2, 4, 8 and 16 mg) of both non‐deuterated glucose and glucose‐6,6‐d2 in 5 mL of water were used and the emission of the acetaldehyde and the ethanol were observed as a function of time. The ethanol and acetaldehyde concentrations in the headspace were obtained from the magnitudes of their characteristic ions on the accumulated SIFT mass spectra and, when the deuterated glucose was used, characteristic singly and doubly deuterated ions were obvious. This study indicates, as expected, that ethanol is the major species generated and that acetaldehyde is a relatively minor component of the headspace and a very minor component of the liquid phase. We estimate that about 108 ethanol molecules are produced per minute per cell in this yeast fermentation process. The distribution of the non‐deuterated and partially deuterated ethanol under these fermentation conditions is observed to be C2H5OH (66 ± 4)%, C2H4DOH(6 ± 1)%, C2H3D2OH(28 ± 4)%, and the analogous distribution for the acetaldehyde is the same, within error. These results indicate that the D atoms in the glucose‐6,6‐d2 are mostly retained by the 6‐C atom, but the appearance of the singly deuterated ethanol and acetaldehyde indicates that some D/H mixing must be occurring in the enzymatic reactions. The results of this study illustrate the potential and power of on‐line SIFT‐MS analysis in this area of research. Copyright © 2001 John Wiley & Sons, Ltd.
Derivatization for liquid chromatography/electrospray mass spectrometry: synthesis of tris(trimethoxyphenyl)phosphonium compounds and their derivatives of amine and carboxylic acids
Authors: Leavens William J , Lane Stephen J , Carr Richard M , Lockie Andrea M , Waterhouse Ian
Published: January 2005

A simple method for the derivatization of primary amines and carboxylic acids with tris(trimethoxyphenyl)phosphonium (TMPP) reagents to enhance their detection by electrospray mass spectrometry (ESI‐MS) has been developed. The synthesis of novel TMPP reagents and their stable isotopically labelled analogues is described. Through the use of stable isotopically labelled TMPP ‘tags’, incorporation of a doublet (1:1, 1H/2H or 12C/13C) into the target molecule can be achieved, enabling the use of isotopic target analysis to detect compounds of unknown molecular weight but with a characteristic isotope pattern and accurate mass difference. Copyright © 2002 John Wiley & Sons, Ltd.
Dual parallel electrospray ionization and atmospheric pressure chemical ionization mass spectrometry (MS), MS/MS and MS/MS/MS for the analysis of triacylglycerols and triacylglycerol oxidation products
Authors: Byrdwell Wm. Craig , Neff William E.
Published: January 2005

Two mass spectrometers, in parallel, were employed simultaneously for analysis of triacylglycerols in canola oil, for analysis of triolein oxidation products, and for analysis of triacylglycerol positional isomers separated using reversed‐phase high‐performance liquid chromatography. A triple quadrupole mass spectrometer was interfaced via an atmospheric pressure chemical ionization (APCI) interface to two reversed‐phase liquid chromatographic columns in series. An ion trap mass spectrometer was coupled to the same two columns using an electrospray ionization (ESI) interface, with ammonium formate added as electrolyte. Electrospray ionization mass spectrometry (ESI‐MS) under these conditions produced abundant ammonium adduct ions from triacylglycerols, which were then fragmented to produce MS/MS spectra and then fragmented further to produce MS/MS/MS spectra. ESI‐MS/MS of the ammoniated adduct ions gave product ion mass spectra which were similar to mass spectra obtained by APCI‐MS. ESI‐MS/MS produced diacylglycerol fragment ions, and additional fragmentation (MS/MS/MS) produced [RCO]+ (acylium) ions, [RCOO + 58]+ ions, and other related ions which allowed assignment of individual acyl chain identities. APCI‐MS of triacylglycerol oxidation products produced spectra like those reported previously using APCI‐MS. APCI‐MS/MS produced ions related to individual fatty acid chains. ESI‐MS of triacylglycerol oxidation products produced abundant ammonium adduct ions, even for those molecules which previously produced little or no intact molecular ions under APCI‐MS conditions. Fragmentation (MS/MS) of the [M + NH4]+ ions produced results similar to those obtained by APCI‐MS. Further fragmentation (MS/MS/MS) of the diacylglycerol fragments of oxidation products provided information on the oxidized individual fatty acyl chains. ESI‐MS and APCI‐MS were found to be complementary techniques, which together contributed to a better understanding of the identities of the products formed by oxidation of triacylglycerols. Copyright © 2002 John Wiley & Sons, Ltd.
Structural isomer differentiation of 1,6‐diaza‐3,8‐dioxabicyclo[4.4.1]undecane and N,N′‐methylenebis(oxazolidine) by mass spectrometry
Authors: Monnier Valérie , Libot Francine , Aitken David J. , Husson Henri‐Philippe , Lesage Denis , Fournier Françoise , Tabet Jean‐Claude
Published: January 2005

The title compound types are structural isomers. The absence of literature studies dealing with the mass spectrometric gas‐phase behavior of such compounds prompted a search for the best conditions for differentiation between the two prototype examples (R,R)‐5,10‐diphenyl‐1,6‐diaza‐3,8‐dioxabi‐cyclo[4.4.1]undecane and N,N′‐methylenebis[(R)‐4‐phenyloxazolidine]. Attempts to differentiate between the isomers by NMR were inconclusive and X‐ray crystallography had to be used. The best mass spectrometric results were obtained using gas‐phase ionization techniques, particularly chemical ionization, whereby protonated molecules were observed. The fragmentation pathways were elucidated from MS/MS studies and from experiments performed on hexadeuterated samples of each compound. Copyright © 2002 John Wiley & Sons, Ltd.
Study of the neurotransmitter dopamine and the neurotoxin 6‐hydroxydopamine by electrospray ionization coupled with tandem mass spectrometry
Authors: Hao Chunyan , March Raymond E. , Croley Timothy R. , Chen Su , Legault M. Glenn , Yang Paul
Published: January 2005

Electrospray ionization combined with tandem mass spectrometry has been applied to a study of dopamine and 6‐hydroxydopamine, an important neurotransmitter and a well‐known neurotoxin, respectively. Both protonated and deprotonated molecules were observed for the two compounds. Upon collision‐induced dissociation of protonated and deprotonated 6‐hydroxydopamine molecules, the number of fragmentation pathways observed was greater than that observed with protonated and deprotonated dopamine molecules; the greater proclivity to fragment of the former is due to the 6‐substituted hydroxyl group, which is para to the 3‐OH group and ortho to the CH2CH2NH2 group. Furthermore, 6‐hydroxydopamine showed a greater propensity to oxidize than did dopamine when sample solutions were kept uncovered in the air for 24 h prior to mass spectrometric examination. Radical structures of the four main oxidation products of 6‐hydroxydopamine have been suggested on the basis of their product ion mass spectra; one or more of these oxidation products may be responsible for the cytotoxic property of 6‐hydroxydopamine. Copyright © 2002 John Wiley & Sons, Ltd.
Ion dispersion near parallel wire grids in orthogonal acceleration time‐of‐flight mass spectrometry: predicting the effect of the approach angle on resolution
Authors: Lewin Mark , Guilhaus Michael , Wildgoose Jason , Hoyes John , Bateman Bob
Published: January 2005

Ions experience small deflections in the vicinity of grids in accelerators and ion mirrors in time‐of‐flight (TOF) mass spectrometers. Recent experiments with an orthogonal acceleration (oa) TOF instrument have verified that the effect can significantly degrade resolution when ions approach grids at an angle deviating from 90 °. The phenomenon becomes significant only when ions have components of velocity at right angles to the wires of the grids. A model is presented in this study to predict this phenomenon for parallel wire grids. The fractional energy spread of ions (calculated in the static TOF‐spectrometer frame of reference) scales directly with the approach angle of ions to the grid (as measured from normal approach). The energy spread also scales with the range of angles that is a consequence of the focusing effect in each gap between the wires of the grid. The equations imply that closely spaced parallel wire grids are best for deployment in oa‐TOF systems where non‐zero approach angles are unavoidable. Such grids are relatively impractical to manufacture and support but rectangular repeat cell grids with relatively few wires at right angles to the source axis are shown experimentally to introduce minimal energy spread. When these grids are rotated by 90 °, the resolution measured in a Q‐TOF spectrometer is degraded in approximate agreement with the parallel wire model. A practical implication of this work is that grid transmissions in oa‐TOF systems may be significantly increased without loss of resolution. Improvements of ∼200% (V‐mode) and ∼400% (W‐mode) in ion transmission were obtained in this study without compromising resolution. This was achieved with ∼73% transmission grids and greater potential improvements in transmission are being realised since this study with ∼89% transmission grids having similar geometry. Copyright © 2002 John Wiley & Sons, Ltd.
Pyrolysis‐gas chromatography/mass spectrometry of pitch fractions recovered from preparative size exclusion chromatography: structural differences with increasing molecular size
Authors: Islas C. A. , Suelves I. , Carter J. F. , Herod A. A. , Kandiyoti R.
Published: January 2005

A sample of high‐temperature coal tar pitch has been fractionated by preparative scale size exclusion chromatography (SEC). Twenty‐four fractions corresponding to narrow molecular mass distributions were collected at sequential elution times of 3 minutes. The preparative scale column is thought to have filtered out most of the very large molecular mass material and the analysis focused on smaller mass components. The recovered fractions were characterised by analytical SEC. Pyrolysis‐gas chromatography/mass spectrometry (pyrolysis‐GC/MS) of the fractions was used to evaluate changes in main structural features with changing molecular size.

As expected, analytical SEC of the fractions showed a systematic shift to smaller molecular sizes with increasing elution time. UV‐fluorescence spectra of the samples showed parallel structural shifts to shorter wavelengths and gains in intensity with increasing elution times. Pyrolysis‐GC/MS showed parent polycyclic aromatic components considered typical of pitch. The major fragments detected were pyrenes and fluoranthenes (m/z 202) and chrysenes (m/z 228). Benzopyrenes (m/z 252) and larger aromatics were not prominent amongst the pyrolysis products. Taken together, molecular structures were found to change significantly from fraction to fraction, but no systematic pattern emerged with changing elution time. Some components were identified as having formed during the analytical pyrolysis procedure itself. As aromatic products larger than dibenzopyrene (m/z 302) would not elute from the column, detected fragments are thought to have detached from larger pitch molecules.

The pyrolysis of the largest species gave only alkanes and alkenes, with the aromatic fragments thought to be too large to elute through the GC column. The work provides information regarding the aromatic groups that are readily lost from larger molecules. Larger aromatic structures are thought to condense (to char) during the analytical pyrolysis step; the method is limited in not being able to provide information about their structural features. Copyright © 2002 John Wiley & Sons, Ltd.
Direct analysis of highly oxidised organic aerosol constituents by on‐line ion trap mass spectrometry in the negative‐ion mode
Authors: Warscheid Bettina , Hoffmann Thorsten
Published: January 2005

On‐line ion trap mass spectrometry (ITMS) enables the characterisation of constituents of biogenic secondary organic aerosols in complex organic reaction mixtures. This real‐time analysis is achieved by directly introducing the airborne particles into the ion source of the mass spectrometer. Negative‐ion chemical ionisation at atmospheric pressure (APCI(−)) was used as the ionisation method of choice. The aerosols were generated from the gas‐phase ozonolysis of two C10H16‐terpenes (α‐pinene and limonene), and investigated by performing on‐line APCI(−)−ITMSn. Highly oxidised compounds were tentatively identified as important particle‐phase products. Based on recent investigations of low‐energy collision‐induced dissociation pathways of a wide range of deprotonated multifunctional carboxylic acid species derived from monoterpene precursors (Warscheid B, Hoffmann T. Rapid Commun. Mass Spectrom. 2001; 15: 2259), the formation of structurally different C10H16O5 and C10H16O6 species, such as acidic esters from α‐pinene and aldo‐hydroxycarboxylic acids from limonene, is proposed. Copyright © 2002 John Wiley & Sons, Ltd.
High accuracy mass measurement of peptides with internal calibration using a dual electrospray ionization sprayer system for protein identification
Authors: Zhou Feng , Shui Wenqing , Lu Yu , Yang Pengyuan , Guo Yinlong
Published: January 2005

A dual‐ESI‐sprayer system was constructed and applied to achieve high accuracy of peptide mass measurement for protein identification by means of peptide mapping. Sample was introduced in one sprayer, and reference in the other, thus making internal calibration possible greatly enhancing the mass accuracy. Several samples were utilized to evaluate the reliability of this dual‐ESI‐sprayer system. The range of mass errors was 0.16–5.37 ppm. The peptide masses of tryptic digests of myoglobin (horse) were measured by the HPLC/dual‐ESI‐MS system, with mass deviations ranging from 0.01–7.67 ppm, and about 75% mass deviations below 5 ppm with 40% below 1 ppm. These peptide masses were utilized to perform database searching for protein identification, and compared to results obtained by external calibration. This comparison showed that the internal calibration provides a more reliable method of protein identification, with a much smaller number of required peptides for matching, and with less CPU time consumed for database searching. Copyright © 2002 John Wiley & Sons, Ltd.
Novel phosphoryl derivatization method for peptide sequencing by electrospray ionization mass spectrometry
Authors: Chen Jing , Chen Yi , Gong Peng , Jiang Yang , Li Yan‐Mei , Zhao Yu‐Fen
Published: January 2005

A one‐step phosphoryl derivatization method has been used in a peptide sequencing procedure for electrospray ionization tandem mass spectrometry (ESI‐MS/MS). The sodiated derivatized peptides exhibit very simple dissociation patterns, in which two kinds of fragment ions, [bn + OH + Na]+ and [an + Na]+, are formed. Since the amino acid residues are lost sequentially from the C‐terminus, peptide sequences can be identified easily. The fragmentation efficiency of peptides increased as a result of the phosphorylation, and also provided peaks of useful intensity at lower m/z. A peptide with lysine at the C‐terminus was derivatized and analyzed by ESI‐MS/MS. Similar mass spectra, from which the sequence could be read out, were obtained. This is a novel derivatization method yielding neutral derivatives that should be suitable for peptide sequencing by LC/ESI‐MS/MS. Copyright © 2002 John Wiley & Sons, Ltd.
Improved method for the simultaneous determination of d4T, 3TC and ddl intracellular phosphorylated anabolites in human peripheral‐blood mononuclear cells using high‐performance liquid chromatography/tandem mass spectrometry
Authors: Becher François , Pruvost Alain , Goujard Cécile , Guerreiro Catherine , Delfraissy J.‐F. , Grassi Jacques , Benech Henri
Published: January 2005

There is still a need for direct determination (i.e. without dephosphorylation) of nucleoside reverse transcriptase inhibitor (NRTI) triphosphorylated nucleotides in the peripheral‐blood mononuclear cells (PBMCs) of HIV‐positive patients. The objective of this paper was first to improve our previously described direct liquid chromatography/tandem mass spectrometry (LC/MS/MS) assay for stavudine triphosphate (d4T‐TP). Preparation of PBMCs was modified to reduce degradation of d4T‐TP during cell preparation and to simplify this step for routine use in clinical units. The performance of several HPLC columns was compared in order to improve the stability of peak shape over time. The SMT C18 column was replaced by a Supelcogel ODP‐50, thereby reducing two‐fold the concentration of the first standard. Various internal standards were compared to optimize peak shape and remove an interfering peak in LC. 2‐Chloroadenosine 5′‐triphosphate was chosen as the most appropriate internal standard. Substitution of the narrowbore column by a microbore column (150 × 0.32 mm) is also presented and discussed. Secondly, this improved method was successfully applied to the simultaneous determination of d4T‐TP, dideoxyadenosine triphosphate (ddA‐TP) and lamivudine triphosphate (3TC‐TP) in PBMCs, which is useful in view of the common use of NRTI combinations. The method was subsequently applied to clinical samples from HIV‐positive patients receiving antiretroviral therapy containing d4T, ddl and/or 3TC. This method can be used simply and routinely on approximately 200 samples per week, using commercially available instruments and with a simple cell lysis as sample treatment. Copyright © 2002 John Wiley & Sons, Ltd.
A new linear ion trap mass spectrometer
Authors: Hager James W.
Published: January 2005

Characteristics of mass selective axial ion ejection from a linear quadrupole ion trap in the presence of an auxiliary quadrupole field are described. Ion ejection is shown to occur through coupling of radial and axial motion in the exit fringing fields of the linear ion trap. The coupling is efficient and can result in extraction of as much as 20% of the trapped ions. This, together with the very high trapping efficiencies, can yield high sensitivity mass spectral responses. The experimental apparatus is based on the ion path of a triple quadrupole mass spectrometer allowing either the q2 collision cell or the final mass analysis quadrupole to be used as the linear trap. Space charge induced distortions of the mass resolved features while using the pressurized q2 linear ion trap occur at approximately the same ion density as reported for conventional three‐dimensional ion traps. These distortions are, however, much reduced for the lower pressure linear trap possibly owing to the proposed axial ejection mechanism that leads to ion ejection only for ions of considerable radial amplitude. RF heating due to the high ejection q‐value and the low collision frequency may also contribute. Two hybrid RF/DC quadrupole‐linear ion trap instruments are described that provide high sensitivity product ion scanning while operated in the linear ion trap mode while also retaining all conventional triple quadrupole scan modes such as precursor ion and neutral loss scan modes. Copyright © 2002 John Wiley & Sons, Ltd.
Determination of rare earth elements in urine by electrothermal vaporization inductively coupled plasma mass spectrometry
Authors: Bettinelli Maurizio , Spezia Sandro , Terni Cesarina , Ronchi Anna , Balducci Claudio , Minoia Claudio
Published: January 2005

A method was developed for the determination of rare earth elements (REEs) in urine with electrothermal vaporization inductively coupled plasma mass spectrometry (ETV‐ICPMS). The undiluted sample was directly injected into the graphite tube and trifluoromethane (Freon‐23) was used as chemical modifier in order to reduce the vaporization temperature and the memory effect of most of the lanthanides. The detection limits were in the range 1–10 ng/L with relative standard deviation of 3–5% at concentration levels of 1µg/L, and less than 10–15% at 100 ng/L. Two different procedures, external calibration and a standard additions method, were evaluated to measure the concentration levels of lanthanides in the urine samples and the second procedure was considered to be the best choice for calibration in this work. The level of REEs in urine of 50 healthy volunteers was in the range 5–20 ng/L, above the detection limit of ETV‐ICPMS. Copyright © 2002 John Wiley & Sons, Ltd.
A straightforward means of coupling preparative high‐performance liquid chromatography and mass spectrometry
Authors: Cai Hong , Kiplinger Jeffrey P. , Goetzinger Wolfgang K. , Cole Roderic O. , Laws Kathrine A. , Foster Marc , Schrock Audrey
Published: January 2005

Flow splitting to a mass spectrometer is a common way of coupling a highly specific detector to preparative or semi‐preparative high‐performance liquid chromatography (HPLC) purification of combinatorial libraries, drug metabolites, and characterizable impurities. The sensitive mass spectrometer consumes only a small fraction of the analyte while providing online structure‐specific detection, and its output can thus be used to trigger collection of the desired fraction. Coupling mass spectrometry to preparative HPLC is difficult due to the susceptibility of the detector to fouling under conditions of high analyte concentration or solute amount, or to changes in solvent composition. We report here on a device, the mass rate attenuator (MRA), which automatically produces split ratios over a range of 100:1 to 100 000:1 under programmable user control. The MRA is a flow‐control device that periodically gates a small aliquot from one liquid stream into another. The design allows the user to set the frequency of the gating without interruption of the HPLC flow stream. The MRA also allows control of the volume of the aliquot that is transferred between the flow streams. This additional control, compared to passive splitting devices, facilitates optimization of the tubing connecting the separation, detection and collection events. We demonstrate that such optimization can reduce the volume of the collected fraction without compromising recovery, thus reducing the time spent in evaporating solvents to reclaim purified products. Copyright © 2002 John Wiley & Sons, Ltd.
Detecting aristolochic acids in herbal remedies by liquid chromatography/serial mass spectrometry
Authors: Kite Geoffrey C. , Yule Marianne A. , Leon Christine , Simmonds Monique S. J.
Published: January 2005

Targeted liquid chromatography/serial mass spectrometry (LC/MS/MS) analysis, using a quadrupole ion‐trap mass spectrometer, permitted the detection of aristolochic acids I and II in crude 70% methanol extracts of multi‐component herbal remedies without any clean‐up or concentration stages. The best ionisation characteristics were obtained using atmospheric pressure chemical ionisation (APCI) and by including ammonium ions in the mobile phase. Limits of detection for aristolochic acids were influenced by the level of interference created by other components in the sample matrix. They were determined to be between 250 pg and 2.5 ng on‐column within a matrix containing compounds extracted from 2 mg of herbal remedy. With a herbal remedy that only permitted the higher limit of detection, this sensitivity was sufficient to detect the aristolochic acids extracted from 0.1% dry weight of Aristolochia manshuriensis included in the preparation. Copyright © 2002 John Wiley & Sons, Ltd.
Multi‐stage tandem mass spectrometry of metal cationized leucine enkephalin and leucine enkephalin amide
Authors: Barr J. M. , Van Stipdonk M. J.
Published: January 2005

We have examined the multi‐stage collision induced dissociation (CID) of metal cationized leucine enkephalin, leucine enkephalin amide, and the N‐acetylated versions of the peptides using ion trap mass spectrometry. In accord with earlier studies, the most prominent species observed during the multi‐stage CID of alkali metal cationized leucine enkephalin are the [bn + 17 + Cat]+ ions. At higher CID stages (i.e. >MS4), however, dissociation of the [b2 + 17 + Cat]+ ion, a cationized dipeptide, results in the production of [an − 1 + Cat]+ species. The multi‐stage CID of Ag+ cationized leucine enkephalin can be initiated with either the [bn − 1 + Ag]+ or [bn + 17 + Ag]+ ions produced at the MS/MS stage. For the former, sequential CID stages cause, in general, the loss of CO, and then the loss of the imine of the C‐terminal amino acid, to reveal the amino acid sequence. Similar to the alkali cationized species, CID of [b2 − 1 + Ag]+ produces prominent [an − 1 + Ag]+ ions. The multi‐stage CID of argentinated peptides is reminiscent of fragmentation observed for protonated peptides, in that a series of (bn) and (an) type ions are generated in sequential CID stages. The Ag+ cation is similar to the alkali metals, however, in that the [bn + 17 + Ag]+ product is produced at the MS/MS and MS3 stages, and that sequential CID stages cause the elimination of amino acid residues primarily from the C‐terminus. We found that N‐acetylation of the peptide significantly influenced the fragmentation pathways observed, in particular by promoting the formation of more easily interpreted (in the context of unambiguous sequence determination) dissociation spectra from the [b2 + 17 + Li]+, [b2 + 17 + Na]+ and [b2 − 1 + Ag]+ precursor ions. Our results suggest, therefore, that N‐acetylation may improve the efficacy of multi‐stage CID experiments for C‐terminal peptide sequencing in the gas phase. For leucine enkephalin amide, only the multi‐stage CID of the argentinated peptide allowed the complete amino acid sequence to be determined from the C‐terminal side. Copyright © 2002 John Wiley & Sons, Ltd.
Electrospray liquid chromatography/mass spectrometry fingerprinting of Acanthophis (death adder) venoms: taxonomic and toxinological implications
Authors: Fry Bryan G. , Wickramaratna Janith C. , Hodgson Wayne C. , Alewood Paul F. , Kini R. M. , Ho Hao , Wüster Wolfgang
Published: January 2005

Death adders (genus Acanthophis) are unique among elapid snakes in both morphology and venom composition. Despite this genus being among the most divergent of all elapids, the venom has been historically regarded as relatively quite simple. In this study, liquid chromatography/mass spectrometry (LC/MS) analysis has revealed a much greater diversity in venom composition, including the presence of molecules of novel molecular weights that may represent a new class of venom component. Furthermore, significant variation exists between species and populations, which allow for the LC/MS fingerprinting of each species. Mass profiling of Acanthophis venoms clearly demonstrates the effectiveness of this technique which underpins fundamental studies ranging from chemotaxonomy to drug design. Copyright © 2002 John Wiley & Sons, Ltd.
Detection and identification of quinonemethide triterpenes in Peritassa campestris by mass spectrometry
Authors: Rodrigues‐Filho Edson , Barros Fábio A. P. , Fernandes João B. , Braz‐Filho Raimundo
Published: January 2005

Analysis of tingenone and tingenol quinonemethide triterpenes was made by gas chromatography/mass spectrometry (GC/MS) of their trimethylsilyl (TMS) ethers. An extra TMS group, in addition to those predicted from the known structures, is added to these compounds during the derivatization process. The electron impact mass spectra showed base peaks at m/z 549 and 623, respectively, for the TMS derivatives of tingenone and tingenol, and electrospray (ES) and collision‐activated dissociation (CAD) studies indicate that these ions correspond to losses of a methyl group from the derivatives studied. A mechanism, based on ES‐MS/MS studies, is suggested for the derivatization and fragmentation pattern. Copyright © 2002 John Wiley & Sons, Ltd.
Hydrogen/deuterium exchange for higher specificity of protein identification by peptide mass fingerprinting
Authors: Bienvenut Willy V. , Hoogland Christine , Greco Anna , Heller Manfred , Gasteiger Elisabeth , Appel Ron D. , Diaz Jean‐Jacques , Sanchez Jean‐Charles , Hochstrasser Denis F.
Published: January 2005

Genome sequencing projects produce large amounts of information that could be translated into potential protein sequences. Such amounts of material continuously increase protein database sizes. At present, 22 times more protein sequences are available in the SWISS‐PROT and TrEMBL databases than 8 years ago in SWISS‐PROT. One of the methods of choice for protein identification makes use of specific endoproteolytic cleavage followed by matrix‐assisted laser desorption/ionisation mass spectrometric (MALDI‐MS) analysis of the digested product. Since 1993, when this technique was first demonstrated, the conditions required for a correct identification have changed dramatically. Whilst 4–5 peptides with an uncertainty of 2–3 Da were sufficient for a correct identification in 1993, 10–13 peptides with less than 60 ppm mass error are now required for human and E. coli proteins. This evolution is directly related to the continuous increase in protein database sizes, which causes an increase in the number of false positive matches in identification results. Use of an information complement deduced from the primary protein sequence, in the process of identification by peptide mass fingerprints, can help to increase confidence in the identification results. In this article, we propose the exchange of labile hydrogen atoms with deuterium atoms to provide an alternative information complement. The exchange reaction with optimised techniques has shown an average 95% of hydrogen/deuterium (H/D) exchange on tryptic peptides. This level of exchange was sufficient to single out one or more peptides from a list of potential candidate proteins due to the dependence of H/D exchange on the peptide primary structure. This technique also has clear advantages in the identification of small proteins where direct protein identification is impaired by the limited number of endoproteolytic peptides. Then, information related to primary sequence obtained with this technique could help to identify proteins with high confidence without any expensive tandem mass spectrometry instruments. Copyright © 2002 John Wiley & Sons, Ltd.
Side‐chain radical losses from radical cations allows distinction of leucine and isoleucine residues in the isomeric peptides Gly‐XXX‐Arg
Authors: Wee Sheena , O'Hair Richard A. J. , McFadyen W. David
Published: January 2005

Sequencing of peptides via low‐energy collision‐induced dissociation of protonated peptides typically yields bn and yn sequence ions. The isomeric residues leucine and isoleucine rarely can be distinguished in these experiments since they give bn and yn sequence ions of the same m/z. Siu's pioneering work on electrospray ionization of copper complexes of peptides (Chu IK, Rodriquez CF, Lau TC, Hopkinson AC, Siu KWM. J. Phys. Chem. B 2000; 104: 3393) provides a way of forming radical cations of peptides in the gas phase. This method was used to generate M+· ions of the two isomeric peptides Gly‐Leu‐Arg and Gly‐Ile‐Arg in order to compare their fragmentation reactions. Both radical cations fragment to give even electron y2 and y1 sequence ions as well as side‐chain radical losses of CH3 and CH3CH2 for isoleucine and (CH3)2CH for leucine. In contrast the [M + H]+ and [M + 2H]2+ ions do not allow distinction between the isomeric leucine and isoleucine peptides. Copyright © 2002 John Wiley & Sons, Ltd.
Lyapunov–Krasovskii functionals and frequency domain: delay‐independent absolute stability criteria for delay systems
Authors: Bliman Pierre‐Alexandre
Published: January 2005

The present paper is devoted to the study of absolute stability of delay systems with nonlinearities subject to sector conditions. We construct quadratic candidate Lyapunov–Krasovskii functional, whose decreasingness along trajectories is expressed in terms of linear matrix inequalities. We then show that the feasibility of the latter implies some frequency‐domain conditions, which may be seen as delay‐independent versions of the circle criterion and the Popov criterion. Copyright © 2001 John Wiley & Sons, Ltd.
Global stabilization of chemical reactors with classical PI control
Authors: Alvarez‐Ramirez Jose
Published: January 2005

This paper is devoted to the stabilization of chemical reactors with classical PI control. Roughly speaking, it is proven that if the isothermal dynamics are globally asymptotically stable, global stabilization of the chemical reactor dynamics is achieved via temperature control with classical PI compensation. Copyright © 2001 John Wiley & Sons, Ltd.
An invariant‐based approach to the design of hybrid control systems
Authors: Stiver James A. , Koutsoukos Xenofon D. , Antsaklis Panos J.
Published: January 2005

In this paper, a methodology for hybrid control design is presented. The hybrid systems of interest are characterized by a feedback architecture of a continuous nonlinear plant with a discrete‐event controller. The natural invariants of the continuous dynamics are used to partition the state space into regions and to synthesize simple and efficient control laws. The paper contains a complete description of the approach including a description of the hybrid control system modelling, of the invariant‐based approach for the design of the partition, and of the controller synthesis methodology illustrated by examples. The implementation and optimization of the approach are also discussed. The approach presented in this paper not only describes a viable methodology to hybrid design, but also addresses fundamental issues in hybrid system theory that arise in reachability analysis and verification approaches that are based on partitions of the continuous state space. Copyright © 2001 John Wiley & Sons, Ltd.