Electron Capture Negative Ionization Mass Research Articles

Electron capture negative ion mass spectra of halogenated diphenylethane derivatives

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTElectron capture negative ion mass spectra of halogenated diphenylethane derivativesE. A. Stemmler and Ronald A. HitesCite this: Anal. Chem. 1988, 60, 8, 787–792Publication Date (Print):April 15, 1988Publication History Published online1 May 2002Published inissue 15 April 1988https://doi.org/10.1021/ac00159a011RIGHTS & PERMISSIONSArticle Views98Altmetric-Citations49LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (631 KB) Get e-Alerts Get e-Alerts

Interlaboratory comparison of methane electron capture negative ion mass spectra

The electron capture negative ion (ECNI) mass spectra of 12 compounds were measured on quadrupole and magnetic sector instruments. The compounds were selected as examples of molecules that are often examined by ECNI mass spectrometry. Under similar conditions of sample concentrations and ion source temperatures and pressures, the spectra showed good agreement in the molecular ion mass range. A Hewlett-Packard 5985B quadrupole instrument showed a lower abundance of low mass ions (such as Cl/sup -/) relative to the other instruments. Other sources of spectral variability arose from ion/molecule reactions involving reagent gas impurities and from hydrogen incorporation reactions.

Stable isotope dilution analysis of succinylacetone using electron capture negative ion mass fragmentography: an accurate approach to the pre- and neonatal diagnosis of hereditary tyrosinemia type I

A sensitive and accurate isotope dilution assay using electron capture negative ion mass fragmentography was developed for succinylacetone in amniotic fluid, plasma and urine. The method utilizes (D 4)-5(3)-methyl-3(5)-isoxasole propionic acid as internal standard. Sample pretreatment consisted of oximation at pH < 2 to 5(3)-methyl-3(5)-isoxasole propionic acid, clean up using liquid partition chromatography and further derivatization to the pentafluorobenzyl ester. Control values in plasma revealed a mean x ̄ = 0.044 μ mol/l , range = 0.005−0.163 μmol/l, in urine x ̄ = 0.15 μ mol/l , range 0.01–0.40 μmol/l corresponding to x ̄ = 0.03 μ mol/mmol creat., range 0.01–0.14 μmol/mmol creat., and in amniotic fluid x ̄ = 0.016 μ mol/l , range = 0.001−;0.030 μmol/l. The utility of the method was demonstrated by quantification of succinylacetone in urine from patients with hereditary tyrosinemia type I ( n = 8, excretion range 2.60–493.3 μmol/l corresponding to 0.67–197.3 μmol/mmol creat.) and in two amniotic fluid samples from fetuses affected with this disorder (concentration of succinylacetone 0.085 and 1.50 μmol/l, respectively). Maternal urine from a woman carrying an affected fetus did not show elevated urinary succinylacetone excretion.

Measurement of MeIQx and DiMeIQx in fried beef by capillary column gas chromatography electron capture negative ion chemical ionisation mass spectrometry.

A gas chromatographic-mass spectrometric assay has been developed for the simultaneous measurement of 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) and 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (DiMeIQx) in fried beef. The method employs capillary column gas chromatography, electron capture negative ion chemical ionisation mass spectrometry and a stable isotope labelled analogue of MeIQx (the synthesis of which is described) as common internal standard. Two patties of lean minced beef which had been cooked separately were analysed and found to contain both compounds (patty 1-2.4 ng MeIQx/g meat, 1.2 ng DiMeIQx/g meat; patty 2-1.3 ng MeIQx/g meat, 0.5 ng DiMeIQx/g meat). Neither compound was present in the meat prior to cooking.

A new method for the determination of l-DOPA and 3- O-methyldopa in plasma and cerebrospinal fluid using gas chromatography and electron capture negative ion mass spectrometry

l-3-(3,4-Dihydroxyphenyl)alanine (DOPA) and its 3- O-methyl metabolite (OMD) were measured in plasma and cerebrospinal fluid by a new assay which combines N, O-acetylation of amino acids in aqueous media, preparation of pentafluorobenzyl esters under anhydrous conditions, and analysis by gas chromatography-electron capture negative ion mass spectrometry. The N, O-acetyl, carboxy-PFB derivatives gave abundant carboxylate anions ([M-CH 2C 6F 5] −) which were suitable for sensitive analysis using selected ion monitoring. Plasma and CSF samples were sufficiently purified by a simple organic solvent extraction. Analytical recovery for DOPA was 100.2 ± 3.7% at the level of 100 nmol/l. Analysis of DOPA in plasma was performed with a relative standard deviation of 5%. The limit of quantitation in plasma and CSF was at the sub-nmol/l level. In healthy adults, DOPA concentration in plasma was 9.0 ± 2 nmol/l ( n = 11) and in CSF 3.5 ± 0.9 nmol/l ( n = 9). The concentration of OMD in plasma was 99.1 nmol/l (pool of 24 samples) and 15.3 nmol/l in CSF (pool of 12 samples). Measurement of 5-[ 2H]DOPA and 5-[ 2H]OMD in plasma of a healthy individual who had been orally loaded with 3,5-[ 2H 2]tyrosine (150 mg kg body wt) was possible for several hours after the load.

Analysis of phospholipid molecular species in rat lung as dinitrobenzoate diglycerides by electron capture negative chemical ionization mass spectrometry.

The use of electron capture negative ion desorption chemical ionization mass spectrometry was demonstrated in the analysis of phospholipid molecular species at the 1,3-dinitrobenzoate (DNB) diglyceride derivative. Modification of phosphatidylcholine (PC) or phosphatidylethanolamine (PE) by phospholipase C treatment and acylation of the resultant diglyceride with 3,5-dinitrobenzoylchloride afforded separation of the alkylacyl, alkenylacyl, and diacyl dinitrobenzoate subclasses by thin-layer chromatography (TLC). Separation of alkylacyl DNB into individual molecular species by reverse-phase high-performance liquid chromatography (RPHPLC) was demonstrated. Electron capture desorption chemical ionization of individual molecular species (10-25 ng) from a direct probe yielded a mass spectrum characterized by an intense molecular anion. This molecular anion was the base peak of the spectrum accounting for greater than 80% of the total ionization. From this molecular anion the total carbon number and degree of unsaturation of the fatty chains could be determined. Analysis of fatty acid content of the molecular species allowed unequivocal assignment of structure for the alkyl ether phospholipids. Using selected ion monitoring as little as 0.5 pmol of these species could be detected with a signal-to-noise ratio greater than or equal to 3. This technique was useful in the analysis of low picomolar amounts of molecular species of ether phospholipids in the rat lung. Given an appropriate internal standard, analysis of dynamic changes in turnover, metabolism and precursor product relationships could be undertaken.

Stable isotope dilution analysis of pipecolic acid in cerebrospinal fluid, plasma, urine and amniotic fluid using electron capture negative ion mass fragmentography

A sensitive and accurate stable isotope dilution assay was developed for the measurement of pipecolic acid in body fluids using electron capture negative ion mass fragmentography. The method utilizes [ 2H 11]pipecolic acid as the internal standard. Sample preparation consisted of derivatization in aqueous solution (pH 11.5) of the amine moiety with methyl chloroformate to the N-methylcarbamate, followed by acidic ethyl acetate extraction (pH 2) and further derivatization of the carboxyl moiety to the pentafluorobenzyl ester. Normal values have been determined in cerebrospinal fluid (mean x ̄ = 0.041 μmol/l, range 0.010–0.120 μmol/l), in plasma of at term infants (age < 1 wk, x ̄ = 5.73 μmol/l, range 3.75–10.8 μmol/l; age > 1 wk, x ̄ = 1.46 μmol/l, range 0.70–2.46 μmol/l), in urine of at term infants (age < 6 mth, x ̄ = 32.5 μmol/g. creat., range 9.81–84.5 μmol/g. creat; age > 6 mth, x ̄ = 6.35 μmol/g. creat., range 0.15–13.6 μmol/g. creat.) and in amniotic fluid ( x ̄ = 4.65 μmol/l, range 2.24–8.40 μmol/l). The utility of the method was demonstrated for the pipecolic acid quantification in these biofluids of patients with peroxisomal disorders. As affected fetuses with infantile Refsum's disease and Zellweger syndrome showed no significant elevation of pipecolic acid in their surrounding amniotic fluids, the measurement of pipecolic acid in amniotic fluid seemed not to be useful for prenatal diagnosis in these disorders.

The electron capture negative ion mass spectra of 2,6-dinitroaniline and 2,4-dinitrophenol herbicides and related nitrobenzene derivatives

The electron capture, negative ion mass spectra of a group of 2,6-dinitroaniline and 2,4-dinitrophenol herbicides are presented. In addition, the spectra of a series of mono- and dinitrobenzene derivatives are reported. These compounds exhibit a wide range of fragmentation behaviors. Simple spectra, dominated by intense molecular ions, are observed for certain groups of compounds, while others give spectra dominated by ions which result from ortho interactions and other complex rearrangements. The fragmentation behavior of these compounds is investigated using isotopically labelled compounds and accurate mass measurements. The question of nitro group reduction reactions, under electron capture conditions, is examined using 15N labelled compounds. Electron capture negative ion (ECNI) mass spectrometry is found to be a sensitive and reproducible technique for the identification of nitro compounds.

Electron capture negative ion chemical ionization mass spectrometry of derivatized chlorophenols and chloroanilines.

The electron capture negative ion chemical ionization mass spectra of electrophoric derivatives (perfluoroacyl, pentafluorbenzyl, pentafluorobenzoyl, 3,5-bis(trifluoromethyl)-benzoyl, and (pentafluorophenyl)methanimine) of chloro-substituted phenols and anilines have been investigated. The formation of analyte-specific anions in the spectra of the derivatives is strongly influenced by the nature of the electrophoric group and the summed electron-donating or -with-drawing properties of the aromatic ring substituents. Hammett linear free energy relationships can be used to predict the stability of molecular anions, the direction of fragmentation pathways, and the usefulness of a given derivative for analytical purposes by using selective-ion monitoring. The influence of ion source temperature on the ionically induced dissociation of the derivatives was examined. The relative molar responses of different derivatives under conditions of GC-negative ion chemical ionization mass spectrometry and GC-electron capture detection were comparable.

Trp-P-2 is not detectable in cooked meat and fish.

A gas chromatographic-mass spectrometric assay has been developed for the measurement of 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2) in cooked meat and fish. The method employs capillary column gas chromatography, electron capture negative ion chemical ionisation mass spectrometry, a deuterated analogue of Trp-P-2 as internal standard and has a limit of detection of 0.1 ng Trp-P-2/g food. Four different meats and three types of fish, cooked either by frying on an electric hotplate or by charcoal broiling, were analysed for Trp-P-2. No Trp-P-2 was detected in any of the samples. The assay was modified to give an improved limit of detection of 25 pg Trp-P-2/g food and fried ground beef was re-examined. Once again, no Trp-P-2 was detected in this cooked meat.

Electron capture negative ion chemical ionization mass spectrometry of 1,2,3,4-tetrachlorodibenzo-p-dioxin.

The conditions necessary for reproducible electron capture negative ion chemical ionization (ECNICI) mass spectrometry of polychlorodibenzo-p-dioxins are dependent on the nature and pressure of the reagent gas in the ionization source, as well as on other controllable parameters. A comparison of argon, xenon, sulfur hexafluoride, hydrogen, and helium reagent gases for production of molecular ion M/sup -/, (M - Cl)/sup -/, and the Cl/sup -/ ions from 1,2,3,4-tetrachlorodibenzo-p-dioxin (1,2,3,4-TCDD) shows that intensities of these ions are highly pressure-dependent. These results are rationalized on the basis of pressure-dependent electron thermalization as it affects relative cross sections for resonance and dissociative electron capture. The results from this study show that heavier mass gases give best sensitivities at lower ionization source pressures. Helium as reagent gas gives the most intense molecular ion, and the most linear ion abundance over a large pressure range.

Quantification of nitrendipine by stable isotope dilution and electron-capture negative ion chemical ionization.

The electron-capture properties of nitrendipine, a 1,4-dihydro-pyridine derivative with antihypertensive activity, have been applied to develop a sensitive and specific assay in biological fluids using capillary column gas chromatography and measurement in negative ion chemical ionization mode. The synthesis of a 13C4-labelled analogue suitable as a biological internal standard for bioavailability studies and of a 2H8-labelled analogue, which serves as internal standard, is described. The electron-capture positive ion chemical ionization and electron-capture negative ion chemical ionization mass spectra of nitrendipine and its isotope-labelled analogues are compared. The assay has a detection limit of 100 pg ml-1 plasma with a coefficient of variation of 10.2% using the selected ion monitoring mode and electron-capture negative ion chemical ionization. The method is specific, sensitive and accurate to determine terminal half-life times after intravenous and oral administration of nitrendipine and its 13C-analogue. From the nearly identical plasma concentration-time profile of nitrendipine and its 13C-labelled analogue, an isotopic effect can be excluded. Thus, the synthesized 13C4-analogue should be well suited as a biological standard for bioavailability studies.

BIS-trifluoromethylbenzoyl derivatives for steroid analysis by gas chromatography electron capture negative ion chemical ionisation mass spectrometry

3,5- Bis-trifluoromethylbenzoyl derivatives of eight monohydroxy steroids and eight dihydroxy steroids were synthesised. Under the reaction conditions described, the monohydroxy steroids each gave a single derivative while the dihydroxy steroids, with the exception of corticosterone, showed multiple product formation. The reactivity of hydroxyl groups relative to their stereochemistry is discussed. The electron capture negative ion chemical ionisation mass spectra of these derivatives were recorded. When the derivatised hydroxyl group was alicyclic or aromatic, a molecular ion was normally the base peak in the mass spectrum. Selected ion monitoring of molecular ions indicated that, in certain cases, as little as 1 pg of the parent steroid could be detected. The potential use of this derivative in the quantitative analysis of steroids by gas chromatography-mass spectrometry is discussed.

Combined capillary column gas chromatography/electron capture negative ion chemical ionization mass spectrometry of dihydropyridine calcium antagonists.

Several dihydropyridine calcium antagonists showed intense [M]-. ion peaks as the base peaks and a few fragment peaks in the electron capture negative ion chemical ionization mass spectra. The peak intensities of the [M]-. ion of these antagonists were about 100 times as high as those of the most abundant positive ion. The use of a capillary column connected directly to the ion source prevents the oxidation of these agents in the column and the transfer line. Furthermore, the presence of plasma extract decreases the oxidation of these agents in the injection port. The limits of sensitivity with this technique are 500 fg-5 pg on the column. Combined capillary column gas chromatography/electron capture negative ion chemical ionization mass spectrometry should be suitable for sensitive and specific assays of dihydropyridine calcium antagonists in biological fluids.

Electron capture negative chemical ionization mass spectrometry of chemically oxidized corticosteroids.

A procedure which can be used to increase the electron affinity of corticosteroids for purposes of quantitative analysis is proposed. Ten important corticosteroids are chemically oxidized to 1,4-androstadien-3,11,17-trione or 4-androsten-3,6,17-trione structural steroid analogs to enhance their electrophilicity prior to detection by electron capture negative chemical ionization mass spectrometry. The choice of oxidation reagent, a preliminary assessment of the structure-response relationship of the oxidation products, the optimization of negative ion formation as a function of source temperature and the basis for distinguishing the isomers dexamethasone and betamethasone are addressed.

Determination of acidic catecholamine metabolites in plasma and cerebrospinal fluid using gas chromatography—negative-ion mass spectrometry

A method for the assay of acidic catecholamine metabolites in biological fluids using capillary gas chromatography—electron-capture negative-ion mass spectrometry is described. The method combines acetylation of phenolic hydroxy groups in buffered aqueous solution followed by pentafluorobenzyl ester formation and acetylation of aliphatic hydroxy groups under anhydrous conditions. The resulting per-O-acetyl carboxypentafluorobenzyl esters provided excellent negative-ion mass spectra with intense and diagnostic anions. The sensitivity of the analysis using electron-capture negative-ion mass spectrometry exceeds that using electron-impact mass spectrometry by two to three orders of magnitude. Analysis of acidic catecholamine metabolites in human lumbar cerebrospinal fluid and plasma were performed with good precision (σ rel < 5%) at the low nanomoles per litre level.

Further studies on a site‐specific hydrogen transfer observed in electron capture negative ion chemical ionization mass spectrometry of hydroxyamine pentafluoropropionate derivatives

AbstractFurther studies have demonstrated that the site‐specific hydrogen transfer process involved in the formation of the m/z 145 anion of β‐hydroxyamine pentafluoropropionate (PFP) derivatives observed under electron capture negative ion chemical ionization conditions occurs when the two functional groups are separated by up to five carbon atoms. Deuterium labelling has established that the site specificity, transfer of a hydrogen atom from the carbon adjacent to nitrogen to the OPFP group, is maintained in 4‐amino‐butan‐1‐ol‐N, O‐(PFP)2. The corresponding PFP derivatives of the N‐methylaminoalkanol‐(PFP)2 derivatives lack the m/z 145 species with m/z 163, [OPFP]− being the base anion. Substitution of alkyl groups on the carbon adjacent to oxygen results in a diminution of the ion intensity at m/z 145. with a marked increase in the intensity of m/z 144. The formation of the m/z 145 and 144 anions to proposed to proceed through the intervention of a fluoride ion‐molecule complex as outlined in Scheme 1 with the product ion distribution dependent on which of the two pathways is preferred.

Negative ion chemical ionization mass spectra of α-amino acid oxazolidinone derivatives

Amino acid methyl esters were condensed with 1,3-dichloro-1,1,3,3-tetrafluoroacetone to yield the corresponding oxazolidinone derivatives whose electron capture negative ion methane chemical ionization mass spectra were studied. Anions corresponding to [M + CI]−, (HCI2)− and (CF2CI)2CO)− are discussed in relation to their appearance in the amino acid oxazolidinone spectra. Other common fragmentation modes were the elimination of stable neutral molecules (HCI, HF, CO2) in various combinations from the molecular anion. Aliphatic amino acids having a γ-hydrogen atom relative to the oxazolidinone ring carbonyl group gave an anionic fragment formally equivalent to the McLafferty rearrangement product of positive ion electron impact mass spectrometry.

Bistrifluoromethylaryl derivatives for drug analysis by gas chromatography electron capture negative ion chemical ionization mass spectrometry. Application to the measurement of (N-dicyclopropylmethyl)amino-2-oxazoline in plasma.

A gas chromatographic mass spectrometric assay for (N-dicyclopropylmethyl) amino-2-oxazoline in plasma with a detection limit of 0.1 ng ml-1 was required. Various fluoroaryl derivatives of this compound (code name S3341) were synthesized and their positive ion chemical ionization and electron capture negative ion chemical ionization mass spectra recorded. While fluorobenzyl derivatives of S3341 could be made by heating with the requisite benzyl bromide and diisopropylethylamine in acetonitrile, initial efforts to synthesize corresponding fluorobenzoyl derivatives using a benzoyl chloride in dry ethyl acetate at 60 degrees C were unsuccessful. Mass spectral data indicated that only a fragment of the oxazoline ring was retained in the reaction product and that an N-(2-chloroethyl)benzamide was formed. However, when diisopropylethylamine was included in the reaction mixture, a benzoyl derivative of the complete molecule was obtained. The mechanisms of these reactions are discussed. The negative ion mass spectrum of the 3,5-bistrifluoromethylbenzoyl derivative of S3341 has a base peak at m/z 420 (the molecular ion) and, when this ion is specifically monitored, an amount of derivative equivalent to 1 pg of S3341 can be detected. This allowed the development of an assay for S3341 in plasma with a precision of 9% (SD) at 0.2 ng ml-1 and a lower limit for quantitative determination of 0.1 ng ml-1.

Highly sensitive determination of 5-fluorouracil in human plasma by capillary gas chromatography and negative ion chemical ionization mass spectrometry

A sensitive method using gas chromatography and electron-capture negative ion mass spectrometry for the determination of 5-fluorouracil in plasma is described. 5-Chlorouracil was used as internal standard. Sample clean-up consisted of extraction of the 5-halogenated uracil derivatives with 2-propanol—diethyl ether (22:78, v/v) at pH 6, followed by a back-extraction into aqueous buffer at pH 10.5. Pentafluorobenzyl derivatives of 5-fluoro- and 5- chlorouracil were prepared by extractive alkylation with pentafluorobenzyl bromide with dichloromethane as solvent and tetrabutylammonium as counter-ion. The limit of sensitivity employing this technique was 50 fg on-column. Quantitation in human plasma was possible down to 3 · 10 -9 M (0.39 ng/ml). Mass fragmentographic analysis of 5-fluorouracil in plasma of patients after a bolus injection of 500 mg/m 2 is presented. Plasma concentrations could be determined for at least 8 h after administration.