Mass spectrometric study of persistent acid metabolites of nonylphenol ethoxylate surfactants

A mass spectrometric study was carried out on two nonylphenoxycarboxylic acids, NP1EC and NP2EC (where 1 and 2 indicate the number of ethoxylate units attached to the nonylphenoxy moiety), that are persistent metabolites of widely used nonionic surfactant nonylphenol ethoxylates. In a gas chromatographic/mass spectrometric (GC/MS) study of the methyl esters of NP1EC and NP2EC, two series of fragment ions were observed in electron ionization (EI) mass spectra; m/z (179 + 14n, n = 0-7) and m/z (105 + 14n, n = 0-4) for NP1ECMe and m/z (223 + 14n, n = 0-7) and m/z (107 + 14n, n = 0-5) for NP2ECMe. Similarity indices were used to compare quantitatively the mass spectra of isomers. The mass spectra of two isomers were found to be similar whereas those of the remaining isomers were readily distinguishable from each other. The abundant fragment ions of the two NPECMes were investigated further by GC/MS/MS; product ions resulting from cleavage in the alkyl moiety, cleavage in the ECMe moiety and cleavage in both moieties were detected. Possible structures of the nonyl groups in the two esters were inferred. GC/chemical ionization (CI) mass spectra of the NPECMes with isobutane as reagent gas showed characteristic hydride ion-abstracted fragment ions shifted by 1 Da from those in the corresponding EI mass spectra. The sensitivity of a selected ion monitoring quantitation method for the NPECMes is enhanced under CI conditions compared with that under EI conditions. With electrospray ionization MS/MS, [M - H](-) ions of NP1EC (m/z 277) and NP2EC (m/z 321) were observed and, upon collision-induced dissociation of [M - H](-) of each of the two acids, fragment ions of m/z 219 corresponding to deprotonated nonylphenol, were observed in each case. Based on this observation, a rapid, simple and reliable selected product ion quantitation method is proposed for NP1EC and NP2EC.     

Mass spectra of 3,3-difluoro-1-halo-2-arylcyclopropenes

The electron ionization (EI) mass spectra of a series of 3,3-difluoro-1-halo-2-arylcyclo- propenes (1, 2) give the fragments [M-X](+) (X: Br, Cl) as the base peaks. A comparison of tandem mass spectrometry (MS/MS) profiles of the m/z 151 ions recorded from compounds 1 and 2 and 3-bromo-3,3-difluoro-1-phenylcyclopropyne (5), 1,1,2,2-tetrafluoro-3-phenyl- cyclopropane (6), 1,1,2,2-tetrafluoroindane (7), and 2,3,3-trifluoroindene (8) suggested that the structure of the derived [M-X](+) fragment ion is more likely that of a substituted cyclopropenium ion. The results from calculations using the density functional theory (DFT) method support this MS/MS analysis.     

Mass spectra of some new 3,4-dihydro-2[H]-pyridones

Electrospray ionization (ESI) and tandem mass spectrometry (MS/MS) experiments, as well as electronic impact (EI) and chemical ionization (CI) techniques, have been applied to the title compounds 1a-h. The observation of different fragmentation pathways in the three sets of spectra is in accord with different degrees of internal excitation of the investigated precursors. In ESI (methanol as solvent) and CI (methane as reagent gas) spectra, the MH(+) ion represents the most important peak, while the fragments [M - OH](+) and [M - SO](+) are either the base peak or a very abundant peak in the EI mass spectra of these compounds. ESI-MS/MS experiments on the parent ions [MH](+) show that the loss of a fragment of 140 Da corresponding to p-toluenesulfenic acid is common from all the precursors. As well as competitive pathways, the second generation ions have also been elucidated to allow some observations to be made concerning the relationships between structure type and mass spectrometric characteristics.     

Mass spectral characteristics of okadaic acid and simple derivatives.

Electron ionization (EI), chemical ionization (CI) and fast-atom bombardment (FAB) mass spectra of the marine toxin okadaic acid and its synthetic methyl, pentafluorobenzyl, and trimethylsilyl ester and ether derivatives were generated. Several ionization conditions and ion-processing methods were used to obtain positive- and negative-ion conventional spectra and tandem (MS/MS) spectra. The EI and the positive-ion CI spectra provided fragment ions characteristic of the structure, and the negative-ion CI and FAB spectra provided molecular ions. The addition of alkali salts to the FAB matrix resulted in reduced fragmentation and the formation of intense alkali-metal-cationized molecules. Pentafluorobenzyl ester derivatives provided intense carboxylate ions under electron-capture ionization. Analytically useful MS/MS spectra were obtained by low-energy collision-induced decomposition of the carboxylate anion produced from the tetrasilylated pentafluorobenzylokadaate.     

Mass spectral studies on aryl-substituted N-carbamoyl/N-thiocarbamoyl narcotine and related compounds

Positive ion mass spectral fragmentation of new N-carbamoyl/N-thiocarbamoyl derivatives of narcotine and compounds closely related to it are reported and discussed. The techniques used include electron impact (EI), fast-atom bombardment (FAB), matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) and electrospray ionization tandem mass spectrometry (ESI-MS/MS). Prominent peaks in the mass spectra of these compounds appear to involve C-C bond cleavage beta to the amine nitrogen with loss of the 4,5-dimethoxy(1H)isobenzofuranone moiety from their molecular ions, along with another prominent peak at m/z 382. No molecular ion peaks of these compounds were recorded in EI, whereas intense [M + H]+ ion peaks were observed in FAB and ESI spectra. MALDI also yielded [M + H]+ ion peaks in good agreement with FAB and ESI studies.     

Gas-phase reactions for selective detection of the explosives TNT and RDX

Highly selective gas-phase reactions with ethyl vinyl ether (EVE) of major electron (EI) and chemical ionization (CI) fragment ions of the explosives TNT and RDX have been uncovered. The fragment ion of m/z 210 from TNT undergoes [4(+)+ 2] cycloaddition with EVE to form an oxo-iminium ion of m/z 282, which dissociates by acetaldehyde loss after a [1,5-H] shift to form a quinolynium ion of m/z 238. The fragment ion of m/z 149 from RDX reacts with EVE by a formal vinylation reaction, that is, the elusive cyclic adduct loses ethanol to yield a nitro-iminium ion of m/z 175, which reacts further with EVE to form a second cyclic product ion of m/z 247. Calculations and MS/MS experiments support the proposed structures. These highly characteristic reactions of diagnostic EI and CI fragment ions improve selectivity for TNT and RDX detection.     

Mass-spectrometric studies of new 6-nitroquipazines—serotonin transporter inhibitors

Six synthesized 6-nitroquipazine derivatives were examined by electron ionization (EI) and electrospray ionization (ESI) mass spectrometry in positive and negative ion mode. The compounds exhibit high affinity for the serotonin transporter (SERT) and belong to a new class of SERT inhibitors. The EI mass spectra registered in negative ion mode showed prominent molecular ions for all the compounds studied. All EI mass spectra and all ESI mass spectra showed similar fragmentation pathways of molecular ions, but the pathways differed between EI and ESI. The differences were explained with the aid of theoretical evaluation of the stability of the respective radical ions (EI MS) and protonated ions (ESI MS).     

An overview of the retro-Diels-Alder reaction in semiunsaturated heterocyclic rings: mass spectra of new substituted 1,4,5,6,7,8-hexahydroquinolines and their oxo-analogues 5,6,7,8-tetrahydro-4H-chromenes

Electron impact ionization (EI), chemical ionization (CI), electrospray ionization (ESI) and tandem mass spectrometry (MS/MS) were used to investigate a number of relatively large and structurally related new heterocycles such as substituted 1,4,5,6,7,8-hexahydroquinolines and their oxa-analogues 5,6,7,8-tetrahydro-4H-chromenes. In the EI spectra the hexahydroquinolines undergo the loss of the substituent attached at the C4 position, while the 4H-chromenes undergo a retro-Diels-Alder reaction (RDA) after elimination of the C4 substituent. Under chemical ionization conditions the RDA reaction is observed only for the 4H-chromenes. The ESI-MS/MS spectra reveal results similar to the EI and CI spectra, since the 4H-chromenes undergo RDA reactions while the hexahydroquinolines form a very stable even-electron pyridium ion derived from the loss of the C4 substituent.     

Effects of stepwise excitation on fragmentation of gas phase ions: An especially striking case

Dramatically different fragmentation patterns are obtained for 4-ethyl-2,6,7-trioxa-1-phosphabicyclo-[2.2.2]octane-1-oxide upon electron ionization (EI) and for the corresponding molecular ion on collision-induced dissociation (CID). Two reasons for this behaviour have been discovered. (i) Irreversible multistep isomerization of the molecular ions occurs prior to collisional activation in mass spectrometry/mass spectrometry (MS/MS). Isomerization reactions have been characterized by isotopic labelling and by examining structures of relevant unlabelled and labelled fragment ions by MS/MS. The extent of isomerization can be controlled by varying the amount of internal energy of the molecular ions. This has been done by changing the number of thermalizing collisions which the ions undergo with neutral molecules in the ion source. (ii) When multiple collisions are used to dissociate the molecular ions, the initially stable fragmentation products undergo extensive further decomposition. As a result, abundant phosphorus-containing fragment ions are obtained for the bicyclic phosphate in high-pressure CID, whereas electron ionization leads to predominant hydrocarbon ions. A minor change in the structure of this molecule has major effects on the fragmentation behaviour: high- and low-energy collisional activation spectra of the molecular ion of the corresponding phosphite are identical with the 12 e V EI mass spectrum of the neutral.     

Deuterium exchange studies in the identification of alkylated DNA bases found in urine, by tandem mass spectrometry

Humans are exposed to a large number of carcinogens which may react at various sites throughout the body, including the N-7-, N2-, and O6-positions of guanine. The effects of this are various but may result in depurination and eventual excretion of the modified base in the urine. Various alkylguanine derivatives with substituents at the N-7-, N2- and O6-positions were synthesized and daughter-ion spectra obtained. Apart from the methyl and dialkylguanines all other spectra exhibited an ion at m/z 151 using electron ionization (EI) and m/z 152 using fast-atom bombardment (FAB). The daughter-ion spectra of dialkylguanines contained an ion at m/z 150 (EI). Hence, scans of m/z 150 and 151 using EI, to detect all parent-ions from which they are formed (parent-ion scans) should indicate the presence of alkyl and dialkylguanine bases in a complex biological matrix such as human urine. Parent-ion scans of m/z 150 and 151 (EI) of a partially purified human urine sample exhibited numerous ions, including a prominent ion at m/z 179. A daughter-ion spectrum of m/z 179 revealed fragment ions that suggested the presence of N2-dimethylguanine and an ethylated guanine. Any confusion due to the presence of daughter ions from different alkylguanines in the same spectrum can be resolved by the fact that an ethylated guanine has four exchangeable protons, whereas N2-dimethylguanine has only three. By performing hydrogen/deuterium exchange it is possible to distinguish the N2-dimethylguanine from ethylated guanine isomers.(ABSTRACT TRUNCATED AT 250 WORDS)     

The effects of electron and chemical Ionization Modes on the MS Profiling of Whole Bacteria

Free fatty acid profiling of whole bacteria [Francisella tularensis, Brucella melitensis, Yersinia pestis, Bacillus anthracis (vegetative and sporulated), and Bacillus cereus] was carried out with direct probe mass spectrometry under 70-eV electron ionization (EI) and isobutane chemical ionization in both the positive (CI+) and negative modes (CI-). Electron ionization produced spectra that contained molecular ions and fragment ions from various free fatty acids. Spectra acquired with isobutane chemical ionization in the positive mode yielded molecular ions of free fatty acids as well as ions from other bacterial compounds not observed under EI conditions. Spectra obtained with negative chemical ionization did not contain as much taxonomic information as EI or CI+; however, some taxonomically significant compounds such as dipicolinic acid and poly(3-hydroxybutyrate) did produce negative ions. All ionization modes yielded spectra that could separate the bacteria by Gram-type when observed with principle components analysis (PCA). Chemical ionization in the positive ion mode produced the greatest amount of differentiation between the four genera of bacteria when the spectra where examined by PCA.     

Compatibility of electron ionization and soft ionization methods in gas chromatography/orthogonal time‐of‐flight mass spectrometry

Orthogonal acceleration time‐of‐flight (oa‐TOF) mass spectrometry (MS) was coupled to gas chromatography (GC) to measure ion yields (ratio of ion counts to number of neutrals entering the ion source) and signal‐to‐noise (S/N) in the electron ionization (EI) mode (hard ionization) as well as in the soft ionization modes of chemical ionization (CI), electron capture negative ion chemical ionization (NICI) and field ionization (FI). Mass accuracies of the EI and FI modes were also investigated. Sixteen structurally diverse volatile organic compounds were chosen for this study. The oa‐TOF mass analyzer is highly suited for FI MS and provided an opportunity to compare the sensitivity of this ionization method to the more conventional ionization methods. Compared to the widely used quadrupole mass filter, the oa‐TOF platform offers significantly greater mass accuracy and therefore the possibility of determining the empirical formula of analytes. The findings of this study showed that, for the instrument used, EI generated the most ions with the exception of compounds able to form negative ions readily. Lower ion yields in the FI mode were generally observed but the chromatograms displayed greater S/N and in many cases gave spectra dominated by a molecular ion. Ion counts in CI are limited by the very small apertures required to maintain sufficiently high pressures in the ionization chamber. Mass accuracy for molecular and fragment ions was attainable at close to manufacturer's specifications, thus providing useful information on molecular ions and neutral losses. The data presented also suggests a potentially useful instrumental combination would result if EI and FI spectra could be collected simultaneously or in alternate scans during GC/MS. Copyright © 2009 John Wiley & Sons, Ltd.     

Fragmentation study of protonated chalcones by atmospheric pressure chemical ionization and tandem mass spectrometry

Fragmentation mechanisms of protonated chalcone and its derivatives with different functional groups were investigated by atmospheric pressure chemical ionization with tandem mass spectrometry (MS/MS). The major fragmentation pathways were loss of the phenyl group from the A or B ring, combined with loss of CO. Losses of H(2)O and CO from the precursor ions of [M+H](+) are proposed to occur via rearrangements. Elimination of water from protonated chalcones was observed in all the title compounds to yield a stable ion but it was difficult to obtain skeletal fragmentation of a precursor ion. Loss of CO was found in the MS/MS spectra of all the compounds except the nitro-substituted chalcones. When the [M+H--CO](+) ion was fragmented in the MS/MS experiments, there were distinctive losses of 15 and 28 Da, as the methyl radical and ethylene, respectively. The ion at m/z 130, found only in the nitro-substituted chalcones, was assigned as C(9)H(6)O by Fourier transform ion cyclotron resonance (FTICR)-MS/MS; m/z 130 is a common fragment ion in the electron ionization (EI) spectra of chalcones. In order to more easily distinguish the constitutional isomers of these chalcones, breakdown curves were produced and these provided strong support in this study.     

Elucidation of urinary metabolites of fluoxymesterone by liquid chromatography-tandem mass spectrometry and gas chromatography-mass spectrometry

The suitability of liquid chromatography tandem mass spectrometry (LC-MS/MS) and gas chromatography mass spectrometry (GC-MS) for the elucidation of fluoxymesterone metabolism has been evaluated. Electrospray ionization (ESI) and collision induced dissociation (CID) fragmentation in LC-MS/MS and electron impact spectra (EI) in GC-MS have been studied for fluoxymesterone and two commercially available metabolites. MS(n) experiments and accurate mass measurements performed by an ion-trap analyser and a QTOF instrument respectively have been used for the elucidation of the fragmentation pathway. The neutral loss scan of 20 Da (loss of HF) in LC-MS/MS has been applied for the selective detection of fluoxymesterone metabolites. In a positive fluoxymesterone doping control sample, 9 different analytes have been detected including the parent compound. Seven of these metabolites were also confirmed by GC-MS including 5 previously unreported metabolites. On the basis of the ionization, the CID fragmentation, the accurate mass of the product ions and the EI spectra of these analytes, a tentative elucidation as well as a proposal for the metabolic pathway of fluoxymesterone has been suggested. The presence of these compounds has also been confirmed by the analysis of five other positive fluoxymesterone urine samples.     

苦参生物碱电喷雾质谱分析

用电喷雾离子阱质谱(ESI-ITMS)研究了苦参碱和氧化苦参碱一级质谱电离规律和二级质谱裂解规律。实验结果显示,苦参碱和氧化苦参碱电喷雾一级质谱中均易产生聚合及加合离子,二级质谱中易产生环逐步裂解碎片离子,即结构相似的苦参碱和氧化苦参碱具有相似的电喷雾质谱行为。苦参碱的特征碎片为m/z148和150,氧化苦参碱的特征碎片为m/z248([M H-17] )、m/z247([M H-18] )以及m/z148、m/z150。对苦参对照药材的甲醇提取物进行了电喷雾质谱分析,由一级质谱的准分子离子及其二级质谱碎裂信息对各已知组分进行了结构认证。     

Differentiation of diastereomeric conduramine derivatives under electron ionization and chemical ionization mass spectral conditions

Diastereomeric conduramine derivatives, i.e., (1R,2S,3R/S,6S)-6-(N-carbomethoxyamino) 1,2-O-isopropylidenecyclohex-4-ene-1,2,3-triol (1 and 2) and their O-acetyl derivatives (3 and 4), were studied using gas chromatography (GC) with electron ionization (EI) and chemical ionization (CI). The EI mass spectra of diastereomeric pairs show consistent differences in the relative abundances of characteristic ions. The EI fragmentation patterns are based on precursor/product ion spectra, high-resolution mass spectrometry (HRMS) and deuterium labelling. The CI spectra show differences from the EI spectra, and the isobutane/CI spectra are much simpler than the methane/CI spectra. The differences shown in the CI spectra are similar to those shown in the product ion spectra of [M+H](+) ions generated under electrospray ionization (ESI) conditions. Theoretical calculations are performed to understand the observed differences. The differences in the relative stabilities of molecular ions, or protonated molecules at different sites, can explain the observed differences in the spectra.     

Chromatographic and mass spectral studies of perfluorooctanesulfonate and three perfluorooctanesulfonamides

The chromatographic and mass spectral characteristics of perfluorooctanesulfonate (PFOS) and three nitrogen-substituted perfluorooctanesulfonamides have been obtained. A methyl/phenyl mixed-phase fused-silica capillary column was used for gas chromatographic (GC) analyses, while a C18 reversed-phase microbore column was used for liquid chromatographic (LC) analyses. Mass (MS) and tandem mass (MS/MS) spectra were generated using electron ionization (EI), argon CE, methane positive and negative ion CI, and ES ionization modes. EI spectra of the amides showed ions characteristic of both the fluorinated hydrocarbon and the sulfonamide portion of the molecules. The fragmentation pathway was studied using hydrogen/deuterium exchange, and was thought to involve a cyclic intermediate ion. Formation of molecular ions by CE and protonated molecule ions by CI to obtain molecular weight information was only partially successful. Negative ion ES-MS spectra provided intense [M-H]- anions for the amides, and an [M-K]- anion for PFOS from which molecular weight information could be obtained, while ES-MS/MS produced product ions that could be used to detect the presence of these compounds in biological or environmental samples.     

Mass spectra of new substituted 2-amino-4H-pyrans: a retro-Diels-Alder reaction pattern

New substituted 2-amino-3-cyano-4H-pyrans have been studied by electron ionization (EI), chemical ionization (CI) and electrospray ionization (ESI) mass spectrometry. The retro-Diels-Alder reaction (RDA) is the main fragmentation pattern observed in the EI spectra forming an unsaturated ketone as the diene fragment. In contrast, a different RDA reaction takes place yielding an unsaturated amide as diene fragment together with the unsaturated ketone in the CI spectra. The MS/MS spectra obtained using an ESI source reveal that the favoured fragmentation by collision induced dissociation (CID) is the elimination of the substituent at the C4 position with formation of a stable pyrilium cation.     

Gas chromatography/mass spectrometry determination of amphetamine-related drugs and ephedrines in plasma, urine and hair samples after derivatization with 2,2,2-trichloroethyl chloroformate

A new analytical approach, based on derivatization with 2,2,2-trichloroethyl chloroformate and gas chromatography/mass spectrometry (GC/MS), was investigated for qualitative and quantitative analyses of a large range of amphetamine-related drugs and ephedrines in plasma, urine and hair samples. Sample preparation involved alkaline extraction of analytes from biological samples using Extrelut columns, after addition of the internal standard 3,4-methylenedioxypropylamphetamine (MDPA), and subsequent derivatization to produce 2,2,2-trichloroethylcarbamates. GC/MS analyses, in splitless mode using a slightly polar 30-m capillary column, were performed with quadrupole or ion trap instruments. MS acquisition modes were electron ionization (EI) in full-scan or selected ion monitoring (SIM) modes (quadrupole), and full-scan MS or MS/MS modes with chemical ionization (CI) conditions (ion trap). EI spectra of 2,2,2-trichloroethylcarbamates showed variably abundant molecular ions as well as abundant diagnostic fragment ions, both characterized by ion clusters reflecting the isotope distribution of three chlorine atoms in the derivatized molecules. CI spectra showed abundant protonated molecules. Quantitative studies using EI SIM conditions gave recoveries in the range 74-89%, linear response over ranges of 10-2000 ng/mL (plasma and urine) and 0.20-20 ng/mg (hair), with corresponding limits of detection in the ranges 2-5 ng/mL and 0.1-0.2 ng/mg. Potential applications (following full method validation) include clinical and forensic toxicology, as well as doping control.     

Pyrolysis/chemical ionization mass spectrometry of polymers

Pyrolysis/mass spectrometric studies have been made on polystyrene, poly(vinyl chloride), and poly(methyl methacrylate) with electron ionization (EI) and chemical ionization (CI) mass spectrometry and a variable temperature probe for direct insertion into the source of the mass spectrometer. Similar results obtained with EI and CI mass spectrometry are in agreement with previous experiments. Advantages of the simplification of spectra in the CI made, as well as the advantages of using both techniques for identification of pyrolysis products, are discussed.