Positive Ion Chemical Ionization Research Articles

The sensitive determination of abanoquil in blood by high-performance liquid chromatography/atmospheric pressure ionization mass spectrometry.

A method is described for the determination of abanoquil in human blood. The method is based on high-performance liquid chromatography (HPLC)/atmospheric pressure positive ion chemical ionization mass spectrometry, using (2H3)abanoquil as internal standard. Multiple reaction monitoring is employed for selectivity and sensitivity, which enables quantification over the range 10-500 pg ml-1 with acceptable precision and accuracy. This assay methodology illustrates the versatility of atmospheric pressure ionization/tandem mass spectrometry, in conjunction with HPLC, for the separation and quantification of drugs in the subnanogram per millilitre range.

Electrophoric labelling of nucleosides for sensitive analysis by negative ion chemical ionization gas chromatography/mass spectrometry

The formation and analytical utility of several electrophone derivatives of native and oxidatively modified nucleosides of deoxythymidine and deoxyguanosine were studied. Derivatives include the incorporation of trimethylsilyl, acetyl or perfluoroacyl groups together with pentafluorobenzyl. Acetylation followed by pentafluorobenzylation was the most favourable method. In general, the combined information from the electron impact, positive ion chemical ionization and negative ion chemical ionization spectra was well suited for structure elucidation purposes. The acetyl-pentafluorobenzyl derivative of deoxythymidine was prepared in quantitative yield and was very sensitive on analysis by gas chromatography negative ion chemical ionization. Injection of 0.45 fmol of 3′,5′-bis(O-acetyl)-3-pentafluorobenzyl-deoxythymidine, in multiple ion detection experiments, gave a response with a signal-to-noise ratio larger than 10.

Determination of triazine herbicides in surface and drinking waters by off-line combination of liquid chromatography and gas chromatography-mass spectrometry

Mass spectra of 12 triazines were obtained by electron impact (EI), positive-ion chemical ionization (PCI) and negative-ion chemical ionization (NCI) using methane and isobutane as reagent gases. EI mass spectrometry is more sensitive than PCI and NCI, although the chemical ionization modes increase selectivity markedly. A pre-column packed with polymer stationary phase was employed to preconcentrate surface and drinking water samples. After desorption of the analytes with ethyl acetate, an aliquot was injected directly into the GC-MS system. Atrazine and simizine were found in these samples at 10–80 ppt levels. The limits of detection for both herbicides were below 10 ppt in drinking water.

Collision spectroscopy in isomer characterization: The case of (E)- and (Z)-p-nitrophenyldiazotert-butyl sulphides

The structural characterization of the E and Z isomers of p-nitrophenyl-diazo tert-butyl sulphide has been achieved by means of different ionization methods (electron impact, fast atom bombardment, positive-ion chemical ionization) and collision experiments performed under different kinetic energy regimes (high- and low-energy collisions, angle-resolved mass spectrometry and energy-resolved mass spectrometry). The two compounds give rise to identical fragmentation patterns. Collision experiments, both at low energy and in the keV range at a scattering angle of 0°, in M+· species obtained by electron impact on the two isomers, do not show any significant differences; the same experiments performed with 8 keV ions at a scattering angle of 2° indicate a clear difference in the absolute abundances of the two main daughter ions. High-energy collisions of MH+ ions obtained by fast atom bombardment lead to different spectra at both 0° and 2° scattering angles, proving that the energy deposition in the preselected species is an important parameter. Low-energy collisions with argon of MH+ ions generated by positive-ion chemical ionization (NH4+) give rise to almost identical energy-resolved mass spectra, whereas the same experiments using helium as target gas lead to a clear distinction between the two isomers.

Investigation of lacidipine, a new 1,4-dihydropyridine antihypertensive agent and three chemically related compounds by means of chemical ionization, mass spectrometry and collision-induced dissociation

Chemical ionization of two 1,4-dihydropyridines, lacidipine and its Z-isomer, and their corresponding pyridines in three different reagent gases and the collision-induced dissociation (CID) of their respective mass-selected protonated molecular ions in the collision energy range 10–200 eV were performed on a multiple quadrupole instrument. The weakness of the Breasted acid NH4+ as a protonating agent is clearly manifested in one of the ammonia positive-ion chemical ionization (CI+) mass spectra which displays the addition ion, [M + NH4]+, as the favoured reaction channel. The stereochemistry of the precursor molecules, the exothermicity of the protonation process and the threshold of certain dissociation channels as a function of the collision energy are among the arguments invoked to explain some of the observed differences between the CI+ mass spectra and the CID data of the different isomers investigated. In an attempt to present a more comprehensive study, some high-performance liquid chromatographic retention times and resolutions are also given.

Mass Spectrometry of Prenylated Flavonoids

The fragmentation patterns originating from the degradation of prenyl group(s) in positive ion electron ionization (EI), fast-atom bombardment (FAB) and chemical ionization (CI) mass spectrometry (MS) of prenylated flavonoids were reviewed. The EI spectra showed the characteristic fragmentation patterns reflecting the location of prenyl group in the flavonoid compounds, whereas the FAB and CI spectra showed relatively monotonous patterns. It was described how the EI and FAB fragmentation patterns are useful for the identification of prenylated flavonoids

Characterisation of polysaccharides by in-source pyrolysis positive- and negative-ion direct chemical ionisation-mass spectrometry

Series of oligosaccharide ions have been generated from a range of polysaccharides by the application of in-source pyrolysis mass spectrometry, using both ammonia positive-ion chemical ionisation and negative-ion chlorine-nucleophilic-addition ionisatioin. Glucans with α-(1 → 6),β-(1 → 6),α-(1 → 4), β-(1 → 4), β-(1 → 3), and β-(1 → 2) linkages were studied, together with pentosans, xyloglucans, and an arabinogalactan. The series of ions correspond to intact, desorbed oligosaccharides with a terminal anhydro-sugar unit, and to similar oligosaccharides with attached sugar ring-cleavage fragments. The ions generated are dependent on the position of the linkage and ring size, and retain significant information on the structure of the original polysaccharide.

Determination of an irreversible inhibitor of monoamine oxidase B (MDL 72974A) in human plasma and urine by gas chromatography—positive-ion chemical ionization mass spectrometry

A sensitive and specific assay has been developed for the quantitative measurement in human plasma and urine of the irreversible inhibitor of monoamine oxidase B [( E)-4-fluoro-β-fluoromethylenebenzene-butanamine HCl salt] (MDL 72974A) (I). This assay is based on gas chromatography—mass spectrometry with ammonia as the chemical ionization reagent gas. After addition of 1-fluoro-2-(4-chlorobenzene)-ethanamine HCl salt (MDL 71946A) as the internal standard, plasma (1 ml) and urine (100 μl) samples were extracted using an automated solid—liquid extraction procedure on CN columns. The eluent was dried with a stream of nitrogen, and the residue was derivatized with pentafluoropropionic anhydride. Selected-ion monitoring of the [MNH 4] + ions m/z 361 (I) and 351 (internal standard) was used for quantification. The method yielded a linear response over the concentration range 0.25–100 pmol/ml in plasma with a limit of quantitation of 0.25 pmol/ml. The within-day reproducibility at a concentration of 5 pmol/ml was 4.6% and at a concentration of 50 pmol/ml was 1.3%. The day-to-day reproducibility was 5.2 and 7.0% at concentrations of 10 and 30 pmol/ml, respectively. The method was applied to the quantification of 1 in plasma and urine after the administration of 12-mg doses of I to a healthy male volunteer.

The electron impact, chemical ionization and fast atom bombardment positive ion mass spectra of 1,2-bis(sulfonyl)methylhydrazines

A series of bis(sulfonyl)-1-methylhydrazines were analyzed by positive ion electron impact (EI), chemical ionization (CI) and fast atom bombardment (FAB) mass spectrometry. Since these compounds showed activity against the L1210 leukemia, an understanding of their mass spectral behavior is important should the structural characterization of metabolites be required. FAB proved to be the most useful technique, generally providing abundant protonated molecule ion peaks, in contrast to the weak peaks observed with CI (ammonia or isobutane) and the total absence of molecular ion peaks in the EI mass spectra. In addition, utilizing FAB eliminated the problem of thermal decomposition, which was very difficult to control under EI and CI experimental conditions. Fragments observed in FAB and CI mass spectra were consistent with protonation at the methyl-bearing nitrogen. One can locate the R1 and R2 moieties relative to the methyl-bearing nitrogen in FAB and CI by assigning that nitrogen as the site of protonation, with subsequent elimination of R2SO2H.

Assay of plasma cannabidiol by capillary gas chromatography/ion trap mass spectroscopy following high-dose repeated daily oral administration in humans

Plasma levels of cannabidiol (CBD) were ascertained weekly in 14 Huntington's disease patients undergoing a double-blind, placebo-controlled, crossover trial of oral CBD (10 mg/kg/day=about 700 mg/day) for 6 weeks. The assay procedure involved trimethylsilyl (TMS) derivatization of CBD and the internal standard delta-6-tetrahydrocannabinol (THC), capillary column gas chromatography, ion trap mass spectroscopy in positive ion chemical ionization mode using isobutane, and calculations of CBD levels based on peak ion intensity of the 387 M+H peak of delta-6-THC-TMS and the 459 M+H peak of CBD-2TMS. The sensitivity of the assay was about 500 pg/ml, and the precision was about 10–15%. Mean plasma levels of CBD ranged from 5.9–11.2 ng/ml over the 6 weeks of CBD administration. CBD levels averaged 1.5 ng/ml one week after CBD was discontinued, and were virtually undetectable thereafter. The elimination half-life of CBD was estimated to be about 2–5 days, and there were no differences between genders for half-life or CBD levels. Additionally, no plasma delta-1-THC, the major psychoactive cannabinoid of marijuana, was detected in any subject.

Analysis of 1,1′-sulphonylbis[2-(methylsulphinyl)ethane] and 1-methylsulphinyl-2-[2-(methylthio)ethylsulphonyllethane, metabolites of sulphur mustard, in urine using gas chromatography-mass spectrometry

A method has been developed for the detection of 1,1′-sulphonylbis[2-(methylsulphinyl)ethane] and 1-methylsulphinyl- 2-[2-(methylthio)ethylsulphonyl]ethane, which have been identified as urinary metabolites of sulphur mustard in the rat. The two metabolites were reduced to the single analyte 1,1′-sulphonylbis[2-(methylthio)ethane] by treatment of urine with acidic titanium trichloride. 1,1′-Sulphonyl-bis[2-(methylthio)ethane] was readily extracted from urine by passing through a C 8 reversed-phase extraction column, or by solvent extraction from a solid absorbent tube, and detected by gas chromatography-mass spectrometry using ammonia positive ion chemical ionisation. The limit of detection was 2 ng/ml for 1-ml samples of urine. There were no background levels of analyte in human or rat urine. If man metabolises sulphur mustard by a similar pathway, the detection of these metabolites should constitute firm evidence of an exposure to sulphur mustard.

Positive and negative ion mass spectrometry and rapid isolation with Sep-Pak C 18 cartridges of ten local anaesthetics

The positive ion electron impact (PIEI), positive ion chemical ionization (PICI) and negative ion chemical ionization (NICI) mass spectra and a rapid isolation procedure using Sep-Pak C 18 cartridges are presented for ten local anaesthetics. In the PIEI mode, molecular peaks were very small or missing for most compounds. Peaks at m z 86 due to the diethylaminomethyl or propylaminoethyl group constituted base peaks in six compounds. In the PICI mode, peaks due to M + H and M + C 2H 5 appeared. The cation at m z 86 was also observed for the six compounds. This ion seems useful for the screening of local anaesthetics. In the NICI mode, anions at m z M − H constituted base peaks for all compounds, peaks at m z M + 12 appeared in many compounds. The total ion current in the PIEI and PICI modes generally gave higher sensitivity than in the NICI mode. Local anaesthetics present in whole blood or cerebrospinal fluid (CSF) could be rapidly isolated by use of Sep-Pak C 18 cartridges with chloroform/methanol as an elution solvent. Their detection was possible using wide-bore capillary gas chromatography with SPB-1 and HP-17 wide-bore capillary columns with satisfactory separation from impurities.

Structural characterization of isomeric didehydro amino acids using chemical ionization

The positive-ion mass spectra of a number of didehydro amino acids (DDAA) obtained by electron ionization (EI) and chemical ionization (CI) using different regent gases as well as the collision-induced dissociation (CID) of mass-selected odd-electron ions and/or protonated molecules have been performed on a multiple quadrupole instrument. The positive-ion EI/CI mass spectra presented display a number of differences which are expected from different isomeric structures. Furthermore, differences associated with the proton affinities of the reagent gases are clearly evident in the poisitive-ion chemical ionization mass spectra as well as in some CID spectra of protonated molecules. This investigation demonstrates the suitability of chemical ionization for characterization of isomers of this important class of compounds and underlines the effect of the proton affinity of the reagent gas on the overall character of the positive-ion chemical ionization spectra.

Characterization of cationic surfactant markers and their abiotic degradation products by CGC-EI/PICI MS

The electronic impact (EI) and positive ion chemical ionization (PICI) mechanisms of a variety of environmental relevant secondary and tertiary trialkylamines (TAMs) (NR1R2R3, where Rn=H, CH3, C14H29, C16H33 or C18H37) have been determined. The base peak of EI mass spectra corresponds to the carbon-carbon bond α-cleavage with respect to nitrogen, contrasting with a low abundant molecular ion [M]+. On the other hand, the [M-1]+ was the base peak of the PICI. In addition, the photoproduct composition of irradiated (λ>290 nm) TAMs ((CH3)2NR, R=C16H33 and C18H37) aqueous solutions in the presence of hydrogen peroxide has been characterized by CGC-MS. In this regard, oxidation products in the vicinal carbons with respect to nitrogen and a variety of photolysis products including fatty acids, aldehydes, alkenes, alkanes and 2-methylketones were identified as major components.

Confirmation of chlorotriazine pesticides, their degradation products and organophosphorus pesticides in soil samples using gas chromatography-mass spectrometry with electron impact and positive- and negative-ion chemical ionization

Gas chromatography-mass spectrometry (GC-MS) with electron impact (EI), positive-ion chemical ionization (PCI) and negative-ion chemical ionization (NCI) were applied as confirmatory techniques for residue analysis of chlorotriazine pesticides, their degradation products and organophosphorus pesticides in soil samples. Clean-up was effected using a Florisil column with subsequent analysis by GC with a nitrogen-phosphorus detector. GC-MS with the EI mode of operation is the common mode of confirmation for all the pesticides. Further confirmation by either GC-MS with PCI and NCI for chlorotriazines and organophosphorus pesticides, respectively, is recommended. The method was applied to the determination of residue levels of atrazine, deethylatrazine, deisopropylatrazine, simazine, fenitrothion and tetrachlorvinphos in several soil samples at levels from 5 ng g −1 to 9 μg g −1.

Antibiotic GE2270 A: A novel inhibitor of bacterial protein synthesis. II. Structure elucidation.

GE2270 A, produced by Planobispora rosea ATCC 53773, inhibits Gram-positive bacteria and anaerobes by acting on the bacterial protein synthesis. The structure has been determined by physico-chemical methods applied to the intact molecule and to the main hydrolysis products. Characterization by UV, IR, NMR (double quantum filter COSY), acid-base ionization, elemental analysis and FAB-MS indicated that GE2270 A is a highly modified peptide having MW 1,289 and formula C56H55N15O10S6, and a weak basic function, and that it belongs to the thiazolyl peptide group of antibiotics. Acid hydrolysis yielded a main product (MW 634), responsible for the chromophoric absorption, and a number of hydrolyzed products of lower MW. 13C NMR inverse techniques and MS studies (EI, positive ion chemical ionization, and collision induced dissociation FAB-MS-MS experiments) on GE2270 A, the chromophoric compound, and the other hydrolysis products led to the complete identification of the various amino acid residues and their sequence. Two out of the six chiral centers have been determined. The structure is thought to originate from modification of a chain of 14 amino acids in a process which creates 6 thiazole rings and one pyridine. The modification process also closes the linear polypeptide to form a cyclic part with an attached side-chain. GE2270 A plausibly has a similar biosynthetic origin to that of other thiazolyl peptide antibiotics such as nosiheptide and micrococcin.

Chemical ionization mass spectrometry of bifunctional compounds. III. The behavior of acetylamino and acetoxyl groups.

Positive ion chemical ionization mass spectra were measured for bifunctional compounds of the type p-XCH2-C6H4-CH2Y, where X=NH2 and NHCOCH3, and Y=OH and OCOCH3. The data can be analyzed in semi-quantitative manner in terms of protonation susceptibility and fragmentation capability of each functional groups. The abnormal behavior of N, O-diacetyl compound was explained by the intramolecular proton transfer between two carbonyl oxygen atoms in [MH]+.

The mass spectra of 4-aminophenanthrene and its trifluoroacetic anhydride and perflnoropropionic anhydride derivatives

Several aminophenanthrenes have been examined with electron impact mass spectrometry. The trifluoroacetic anhydride (TFAA) and perfluoropropionic anhydride (PFPA) derivatives of 4-aminophenanthrene have been studied with electron impact as well as both positive and negative ion chemical ionization mass spectrometry utilizing methane as a reagent gas. The resulting mass spectra indicate a loss of water from the derivatives and a mechanism is proposed to account for this loss. The spectra also indicate unique fragmentation patterns associated with the position of the substituent, particularly the four position which is in the region of the molecule termed the bay region. Another interesting aspect is the spectral differences observed for the TFAA and PFPA derivatives of 4-aminophenanthrene. The positive ion chemical ionization mass spectrum of the TFAA derivative indicates an ion [M + H - H2O]+; however, the mass spectrum of the PFPA derivative of 4-aminophenanthrene indicates no water loss from the [M + H]+ ion. The negative ion chemical ionization mass spectra of the two derivatives are also very different. The mass spectrum of the TFAA derivative shows an [M - 18]- ion and the PFPA derivative shows successive losses of HF with no apparent loss of water.

Metabolic activation of 1,2-dibromo-3-chloropropane to mutagenic metabolites: detection and mechanism of formation of (Z)- and (E)-2-chloro-3-(bromomethyl) oxirane

1,2-Dibromo-3-chloropropane (DBCP), a haloalkane nematocide and soil fumigant, is metabolically activated to chemically reactive species that are direct-acting mutagens in a Salmonella typhimurium TA 100 test system. Studies in vitro with rat liver microsomes indicated that oxidation at carbon 3 resulted in the formation of an unstable gem-chlorohydrin that rearranged with elimination of hydrogen bromide to form (Z)-2-chloro-3-(bromomethyl)oxirane [(Z)-CBPO] and (E)-2-chloro-3-(bromomethyl)oxirane [(E)-CBPO]. Gas chromatography-mass spectrometry (GC-MS) with positive ion chemical ionization (CI) was employed to identify (Z)-CBPO and (E)-CBPO by comparison of characteristic fragment ions in their CI mass spectra with those observed for authentic standards. Quantitative GC-MS methodology was exploited to quantitate the rate of formation of (Z)-CBPO and (E)-CBPO from DBCP and analogues of DBCP specifically deuterated at carbon 1 and carbon 3. The rate of formation of Z- and E-isomers of CBPO was 31 and 33 pmol/(min.mg of protein), respectively, from DBCP; substitution with deuterium at carbon 1 increased the rate of epoxide formation by 50%, whereas CBPO formation could not be detected from a substrate labeled with deuterium at carbon 3. Both epoxides were directly acting mutagens to S. typhimurium TA 100. (Z)-CBPO caused approximately twice as many his+ revertants/nmol compared to (E)-CBPO. Oxidation at carbon 2 of DBCP resulted in the formation of a bifunctional alkylating agent, 1-bromo-3-chloroacetone, presumably via the intermediacy of an unstable gem-bromohydrin.(ABSTRACT TRUNCATED AT 250 WORDS)

Broad Spectrum Analysis of Ionic and Non-Ionic Organic Contaminants in Urban Wastewaters and Coastal Receiving Aquatic Systems

Abstract A comprehensive analytical protocol for the qualitative and quantitative assessment of ionic and non-ionic organic contaminants in urban wastewaters, coastal seawater, and sediments is outlined. Liquid-liquid extraction (LLE) and adsorption onto polymers (polyurethane foam) or macroreticular resins (Amberlite, XAD-2) for the extraction of a wide variety of dissolved contaminants are evaluated. Organic extracts are resolved into fractions of increasing polarity by a combination of silica-alumina adsorption and gel permeation chromatography. HRGC-MS analysis of these fractions, using different ionization techniques, namely electron impact (EI), positive (PICI) and negative ion chemical (NICI) ionization, and the direct use of FAB-MS on the original extracts enabled the identification of a broad spectrum of anthropogenic compounds (290) in the different aquatic compartments. The decoupling of these contaminants between the water-dissolved and particulate phases is discussed.