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Exact Mass Measurement (exact + mass_measurement)
Selected AbstractsExact mass measurement on an electrospray ionization time-of-flight mass spectrometer: error distribution and selective averagingJOURNAL OF MASS SPECTROMETRY (INCORP BIOLOGICAL MASS SPECTROMETRY), Issue 10 2003Jiejun Wu Abstract An automated, accurate and reliable way of acquiring and processing flow injection data for exact mass measurement using a bench-top electrospray ionization time-of-flight (ESI-TOF) mass spectrometer is described. Using Visual Basic programs, individual scans were selected objectively with restrictions on ion counts per second for both the compound of interest and the mass reference peaks. The selected ,good scans' were then subjected to two different data-processing schemes (,combine-then-center' and ,center-then-average'), and the results were compared at various ion count limit settings. It was found that, in general, the average of mass values from individual scans is more accurate than the centroid mass value of the combined (same) scans. In order to acquire a large number of good scans in one injection (to increase the sampling size for statistically valid averaging), an on-line dilution chamber was added to slow down the typically rapid mass chromatographic peak decay in flow-injection analysis. This simple addition worked well in automation without the need for manual sample dilution. In addition, by dissolving the reference compound directly into the mobile phase, manual syringe filling can be eliminated. Twenty-seven samples were analyzed with the new acquisition and process routines in positive electrospray ionization mode. For the best method found, the percentage of samples with RMS error less than 5 ppm was 100% with repetitive injection data (6 injections per sample), and 95% with single injection data. Afterwards, 31 other test samples were run (with MW ranging from 310 to 3493 Da, 21 samples in ESI+ and 10 in ESI, mode) and processed with similar parameters and 100% of them were mass-calculated to RMS error less than 5 ppm also. Copyright © 2003 John Wiley & Sons, Ltd. [source] Matrix effects on accurate mass measurements of low-molecular weight compounds using liquid chromatography-electrospray-quadrupole time-of-flight mass spectrometry,JOURNAL OF MASS SPECTROMETRY (INCORP BIOLOGICAL MASS SPECTROMETRY), Issue 3 2006F. Calbiani Abstract Liquid chromatography (LC) with high-resolution mass spectrometry (HRMS) represents a powerful technique for the identification and/or confirmation of small molecules, i.e. drugs, metabolites or contaminants, in different matrices. However, reliability of analyte identification by HRMS is being challenged by the uncertainty that affects the exact mass measurement. This parameter, characterized by accuracy and precision, is influenced by sample matrix and interferent compounds so that questions about how to develop and validate reliable LC-HRMS-based methods are being raised. Experimental approaches for studying the effects of various key factors influencing mass accuracy on low-molecular weight compounds (MW < 150 Da) when using a quadrupole-time-of-flight (QTOF) mass analyzer were described. Biogenic amines in human plasma were considered for the purpose and the effects of peak shape, ion abundance, resolution and data processing on accurate mass measurements of the analytes were evaluated. In addition, the influence of the matrix on the uncertainty associated with their identification and quantitation is discussed. A critical evaluation on the calculation of the limits of detection was carried out, considering the uncertainty associated with exact mass measurement of HRMS-based methods. The minimum concentration level of the analytes that was able to provide a statistical error lower than 5 ppm in terms of precision was 10 times higher than those calculated with S/N = 3, thus suggesting the importance of considering both components of exact mass measurement uncertainty in the evaluation of the limit of detection. Copyright © 2006 John Wiley & Sons, Ltd. [source] Exact mass measurement on an electrospray ionization time-of-flight mass spectrometer: error distribution and selective averagingJOURNAL OF MASS SPECTROMETRY (INCORP BIOLOGICAL MASS SPECTROMETRY), Issue 10 2003Jiejun Wu Abstract An automated, accurate and reliable way of acquiring and processing flow injection data for exact mass measurement using a bench-top electrospray ionization time-of-flight (ESI-TOF) mass spectrometer is described. Using Visual Basic programs, individual scans were selected objectively with restrictions on ion counts per second for both the compound of interest and the mass reference peaks. The selected ,good scans' were then subjected to two different data-processing schemes (,combine-then-center' and ,center-then-average'), and the results were compared at various ion count limit settings. It was found that, in general, the average of mass values from individual scans is more accurate than the centroid mass value of the combined (same) scans. In order to acquire a large number of good scans in one injection (to increase the sampling size for statistically valid averaging), an on-line dilution chamber was added to slow down the typically rapid mass chromatographic peak decay in flow-injection analysis. This simple addition worked well in automation without the need for manual sample dilution. In addition, by dissolving the reference compound directly into the mobile phase, manual syringe filling can be eliminated. Twenty-seven samples were analyzed with the new acquisition and process routines in positive electrospray ionization mode. For the best method found, the percentage of samples with RMS error less than 5 ppm was 100% with repetitive injection data (6 injections per sample), and 95% with single injection data. Afterwards, 31 other test samples were run (with MW ranging from 310 to 3493 Da, 21 samples in ESI+ and 10 in ESI, mode) and processed with similar parameters and 100% of them were mass-calculated to RMS error less than 5 ppm also. Copyright © 2003 John Wiley & Sons, Ltd. [source] Unimolecular dissociation of protonated trans -1,4-diphenyl-2-butene-1,4-dione in the gas phase: rearrangement versus simple cleavageRAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 17 2006Lianming Wu Fragmentation mechanisms of trans -1,4-diphenyl-2-butene-1,4-dione were studied using a variety of mass spectrometric techniques. The major fragmentation pathways occur by various rearrangements by loss of H2O, CO, H2O and CO, and CO2. The other fragmentation pathways via simple alpha cleavages were also observed but accounted for the minor dissociation channels in both a two-dimensional (2-D) linear ion trap and a quadrupole time-of-flight (Q-TOF) mass spectrometer. The elimination of CO2 (rather than CH3CHO or C3H8), which was confirmed by an exact mass measurement using the Q-TOF instrument, represented a major fragmentation pathway in the 2-D linear ion trap mass spectrometer. However, the elimination of H2O and CO becomes more competitive in the beam-type Q-TOF instrument. The loss of CO is observed in both the MS2 experiment of m/z 237 and the MS3 experiment of m/z 219 but via the different transition states. The data suggest that the olefinic double bond in protonated trans -1,4-diphenyl-2-butene-1,4-dione plays a key role in stabilizing the rearrangement transition states and increasing the bond dissociation (cleavage) energy to give favorable rearrangement fragmentation pathways. Copyright © 2006 John Wiley & Sons, Ltd. [source] Increasing throughput and information content for in vitro drug metabolism experiments using ultra-performance liquid chromatography coupled to a quadrupole time-of-flight mass spectrometerRAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 6 2005Jose Castro-Perez The field of drug metabolism has been revolutionized by liquid chromatography/mass spectrometry (LC/MS) applications with new technologies such as triple quadrupoles, ion traps and time-of-flight (ToF) instrumentation. Over the years, these developments have often relied on the improvements to the mass spectrometer hardware and software, which has allowed users to benefit from lower levels of detection and ease-of-use. One area in which the development pace has been slower is in high-performance liquid chromatography (HPLC). In the case of metabolite identification, where there are many challenges due to the complex nature of the biological matrices and the diversity of the metabolites produced, there is a need to obtain the most accurate data possible. Reactive or toxic metabolites need to be detected and identified as early as possible in the drug discovery process, in order to reduce the very costly attrition of compounds in late-phase development. High-resolution, exact mass measurement plays a very important role in metabolite identification because it allows the elimination of false positives and the determination of non-trivial metabolites in a much faster throughput environment than any other standard current methodology available to this field. By improving the chromatographic resolution, increased peak capacity can be achieved with a reduction in the number of co-eluting species leading to superior separations. The overall enhancement in the chromatographic resolution and peak capacity is transferred into a net reduction in ion suppression leading to an improvement in the MS sensitivity. To investigate this, a number of in vitro samples were analyzed using an ultra-performance liquid chromatography (UPLC) system, with columns packed with porous 1.7,,m particles, coupled to a hybrid quadrupole time-of-flight (ToF) mass spectrometer. This technique showed very clear examples for fundamental gains in sensitivity, chromatographic resolution and speed of analysis, which are all important factors for the demands of today's HTS in discovery. Copyright © 2005 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. [source] Evidence for an aryl migration during the electron impact induced fragmentation of substituted aryloxymethylquinoxalinesRAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 3 2002I. Starke The electron impact (EI) mass spectra of 34 differently substituted 2-phenoxymethyl-, 2-naphthyloxymethyl-, 2-pyridinyloxymethyl- and 2-chinolinyloxymethylquinoxalines were recorded. The fragmentation patterns were examined by metastable ion analysis and exact mass measurements, employing finally also selective deuterium labelling. The inclusion of the substituted aryl ring moiety appears to be important for the fragmentation of the aryloxymethylquinoxalines. A molecular ion rearrangement is proposed for the observed loss of OH· and CHO· radicals. The influence of the different substituents on the aryl ring moiety on the rearrangement in the gas phase and on the resulting fragmentation was investigated. Copyright © 2001 John Wiley & Sons, Ltd. [source] Characterization of a [(O3/2SiMe)x(OSi(OH)Me)y(OSiMe2)z] silsesquioxane copolymer resin by mass spectrometryRAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 22 2001Ron E. Tecklenburg Electrospray ionization Fourier transform ion cyclotron resonance (ESI-FTICR) mass spectrometry and matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry were applied to a complex silsesquioxane-siloxane copolymer resin. The wide-polydispersity starting material was fractionated into 21 separate fractions in order to facilitate the analysis by mass spectrometry. ESI-FTICR exact mass measurements were able to identify the specific oligomers present in the lowest mass fractions and showed that very few unreacted silanol groups remained, that is, topologically closed structures predominated. MALDI-TOFMS was able to show that gel-permeation chromatography substantially underestimated the molecular masses of the higher mass fractions. Mass autocorrelation was able to show that the silsesquioxane monomer appeared only in even numbers in any given oligomer. This is a natural consequence of the highly condensed nature of the resin. Copyright © 2001 John Wiley & Sons, Ltd. [source] | ||||||||||