Negative Chemical Ionization Mass Research Articles

Formation of an unusual MH− ion in the methane negative-ion chemical ionization mass spectra of chlorprothixene and aromatic sulfur compounds

The methane negative-ion chemical ionization (NCI) mass spectrum of chlorprothixene shows an unusual MH− ion. This ion can be accounted for by electron capture followed by H˙ transfer from the reagent gas. The most probable site of electron attachment was concluded to be related to the sulfur atom of the thioxanthene ring based on the observation of analogous ions for structurally related compounds, all containing a heterocyclic sulfur. The MH− ion observed with methane as the reagent gas was shifted to MD− when tetradeuteromethane was used in place of methane. The ratio of [M H]− to MH− did not change with emission current suggesting that the process is independent of the radical concentration in the CI plasma. Consistent with this observation is the lack of CH3˙ or C2H5˙ adduct ions in the NCI mass spectrum and the fact that gold-plating the ion source did not decrease the proportion of MH−. Also, this mechanism is consistent with thermochemical considerations of reactions of a phenyl radical with various alkanes and observations of ions formed by methane NCI from model compounds. Therefore, unlike other MH− ions observed in methane NCI mass spectra, the mechanism of formation does not appear to involve a hydrogen radical addition followed by electron capture.

Secretagogue-induced diacylglycerol accumulation in isolated pancreatic islets. Mass spectrometric characterization of the fatty acyl content indicates multiple mechanisms of generation

Diacylglycerol accumulation has been examined in secretagogue-stimulated pancreatic islets with a newly developed negative ion chemical ionization mass spectrometric method. The muscarinic agonist carbachol induces islet accumulation of diacylglycerol rich in arachidonate and stearate, and a parallel accumulation of 3H-labeled diacylglycerol occurs in carbachol-stimulated islets that had been prelabeled with [3H]glycerol. Islets so labeled do not accumulate 3H-labeled diacylglycerol in response to D-glucose, but D-glucose does induce islet accumulation of diacylglycerol by mass. This material is rich in palmitate and oleate and contains much smaller amounts of arachidonate. Neither secretagogue influences triacylglycerol labeling, and neither induces release of [3H]choline or [3H]phosphocholine from islets prelabeled with [3H]choline. These observations indicate that the diacylglycerol that accumulates in islets in response to carbachol arises from hydrolysis of glycerolipids, probably including phosphoinositides. The bulk of the diacylglycerol which accumulates in response to glucose does not arise from glycerolipid hydrolysis and must therefore reflect de novo synthesis. The endogenous diacylglycerol which accumulates in secretagogue-stimulated islets may participate in insulin secretion because exogenous diacylglycerol induces insulin secretion from islets, and an inhibitor of diacylglycerol metabolism to phosphatidic acid augments glucose-induced insulin secretion.

Isotope dilution gas chromatography—mass spectrometry for the study of eicosanoid metabolism in human blood platelets

Stable isotope dilution gas chromatography—mass spectrometry provides one of the most important techniques for the quantitative measurement of eicosanoids. This technique was aplied to the quantitation of hydroxyeicosatetraenoic acids, hydroxyheptadecatrienoic acid, thromboxane B 2 and prostaglandin F 2α formed during platelet aggregation after stimulation of gel-filtered platelets with thrombin (0.25 U/ml) or collagen (2 μg/ml). Similar amounts of hydroxyheptadecatrienoic acid and thromboxane B 2 were found after platelet activation. The ratio of formation of 12-hydroxyeicosatetraenoic acid to thromboxane B 2 varied from donor to donor. Only small amounts of prostaglandin F 2α (up to 200 pg per 2.0·10 8 platelets) and basic values of 15-hydroxyeicosatetraenoic acid (up to 100 pg per 2.0·10 8 platelets) were measured using gas chromatography with negative ion chemical ionization mass spectrometry. In addition, different stable isotope dilutions were prepared and are discussed in detail.

Negative ions generated by reactions with oxygen in the chemical ionization source. I. Characterization of gas‐phase and wall‐catalyzed reactions of fluorene, anthracene and fluoranthene

AbstractThe methane negative ion chemical ionization (NICI) mass spectra of polycyclic aromatic hydrocarbons are usually dominated by molecular, M− ˙ or M  H− ions; however, ions resulting from additions to M have also been reported. Some of these ions have been observed at [M + 14]− ˙, [M + 15]−, [M + 30]− and [M + 32]−˙ and have been attributed to reactions with either oxygen‐containing impurities in the buffer gas or alkyl radical species generated by ionization of a hydrocarbon buffer gas. In this study, the NICI spectra of fluorene, anthracene and fluoranthene were studied in detail using quadrupole and Fourier transform mass spectrometers. Spectra were acquired when reactive species such as oxygen, water, nitrous oxide and carbon dioxide were added to the nitrogen buffer gas. Experiments with deuterated methane were also carried out. These studies indicated that buffer gas impurities affect the NICI spectra; however, gas‐phase ion‐molecule reactions were not responsible for all of the observed products. In addition to electron‐ and ion‐molecule reactions, ions were observed that resulted from wall‐catalyzed oxidation reactions followed by electron capture. These reactions were enhanced by the addition of oxygen and elevated ion source temperatures. Depending upon the parent PAH structure, oxidation products such as ketones, quinones and anhydrides were formed.

Polychlorinated biphenyl congeners in adipose tissue lipid and serum of past and present transformer repair workers and a comparison group

The concentrations of individual PCB's were determined in both serum and adipose tissue lipid from 35 transformer repair workers currently exposed to PCBs, mainly Aroclor 1260, 17 previous transformer repair workers, and 56 comparison workers never occupationally exposed to PCBs. The analysis used fused-silica capillary gas chromatography with electron capture detector (FSCGC/ECD) and FSCGC with negative ion chemical ionization mass spectrometry to verify PCB congener levels. Eighty-nine PCB peaks were identified and confirmed. More congeners were detected in adipose tissue. In serum approximately 50% of peaks were below the level of detection. Statistical techniques to account for left and interval censoring allowed comparison of concentration distributions even where data were incomplete. We found that unquantifiable levels were unlikely to contribute substantially to the true values for total [PCBs] over and beyond the contribution of the measured values. However, the total serum [PCBs] determined by FSCGC/ECD greatly exceeded that from standard packed cell gas chromatography (PCGC/ECD). The underestimation was less marked for adipose samples. In serum the total [PCBs] was highest in currently exposed workers and lowest in unexposed workers, with past-exposed workers clearly intermediate. In adipose tissue [PCBs] in the currently exposed group was much higher than in the other two groups, in whom the distribution of results was broadly similar. In all worker groups hexachlorinated and heptachlorinated species predominated followed by octachlorinated and pentachlorinated. The relative distribution of individual PCB congeners in the three groups was similar although the amounts varied. The seven major peaks in serum and adipose tissue were 2,3,5,6,3′,4′,5′/2,3,4,5,2′,4′,5′ hepta-CB; 2,3,4,2′,3′,5′ hexa-CB; 2,4,6,3′,4′,5′/ 2,4,5,2′,4′,5′/2,3,4,5,2′,5′ hexa-CB; 2,3,4,5,2′,3′,4′ hepta-CB; 2,3,4,5,2′,3′,5′,6′/2,3,4,5,6,2′,3′,5′, octa-CB; 2,4,5,3′,4′,/3,4,5,2′,3′ penta-CB; and 2,3,4,2′,3′,4′/2,3,5,6,2′,4′,5′/2,3,4,5,2′,4′,6′ multi-CB. The distribution of PCB peaks in our populations differs from that in capacitor workers (exposed to less highly chlorinated PCBs) and from Yu-Cheng patients suggesting differing toxic potentials from PCBs in these three circumstances.

Picogram level determination of medetomidine in dog serum by capillary gas chromatography with negative ion chemical ionization mass spectrometry

This paper describes a new gras chromatographic-mass spectrometric (GS-MS) assay for the determination of medetomidine in serum

Determination of rimantadine and its hydroxylated metabolites in human plasman and urine

A gas chromatographic-mass spectrometric procedure has been developed for the quantitation of the antiviral agent rimantadine and its meta- and para-hydroxylated metabolites in human plasma and urine. The assay utilizes an extractive pentafluorobenzoylation at alkaline pH with cyclohexane saturated with triethanolamine-chloroform (2:1) containing pentafluorobenzoyl chloride, selective ion monitoring, methane negative ion chemical ionization mass spectrometry and stable isotope dilution. The method has been used to measure plasma concentrations of rimantadine, m-hydroxyrimantadine and the two epimers of p-hydroxyrimantadine between 5-250, 5-100 and 2.5-50 ng/ml, respectively. Similarly, the urine concentrations of these measured were between 25-1250, 25-500 and 12.5-250 ng/ml, respectively.

Pharmacokinetics of Rioprostil in Human Plasma as Assayed by Combined Capillary Gas Chromatography-Negative Ion Chemical Ionization Mass Spectrometry

To investigate the pharmacokinetics of rioprostil in man an assay is developed to analyse levels of rioprostil in plasma. After extraction and purification by solid-phase cartridges rioprostil is measured by negative ion chemical ionization mass spectrometry using a deuterated internal standard. The method is validated by a recovery experiment. Levels of rioprostil in the plasma of four volunteers following a single oral dose of 600 micrograms rioprostil are found as always below 100 pg/ml. The data presented here suggest that rioprostil is transformed rapidly in man to its more polar metabolites.

負イオン化学イオン化質量分析法の基礎的検討とその微量成分分析への応用

負イオン化学イオン化質量分析(NCIMS)法について,分析花学的立場から行った基礎的検討およびこれ縞感度かつ(または)高選択的な分析方法として実際試料に適した例について述べる。ハロゲン化物を用いた電子捕獲によるNCIでは,ECDとの応答の相関,生成イオン種とイオン量,正負イオンの生成量比などを検討し, 負イオンの生成効率が分子の電子親和力,反応の活性化エネルギーに支配され,それらの値の大小により生成イオン量が1000倍以上も違うことを明らかにした。C1-を反応イオンとする系ではクロロホルムがもっとも使いやすく,またメタンと混合するとイオン化が安定し熱的に不安定な化合物でもそのスペクトルから分子量を容易に推定することができた。多環芳香族炭化水ニトロアレーン,有機ハロゲン系化合物についてメタンを素,ダイオキシンについて酸素をそれぞれ試薬ガスとしたときのNCIスペクトルの特雛明らかにし,それらを高感度・高選択的に検出するためのデータを得た。またそのままではNCI法の適繭瞬なアルコ一ル,フェノール,アミン,カルボン酸アミノ酸などについて種々の含フッ素誘導体化剤による誘導体化を行い,最適誘導体化剤,正負イオン量比などNCI法を適用するために有用な知見を得た。この方法の応用として,環境汚染物質や代謝関連物質を中心測定方法を検討し,実際試料の測定を行った。

Assay for N τ-methylimidazoleacetic acid, a major metabolite of histamine, in urine and plasma using capillary column gas chromatography-negative ion mass spectrometry

A gas chromatographic-mass spectrometric assay has been developed for the measurement of N τ-methylimidazoleacetic acid in urine and plasma. The method uses the isopropyl ester 3,5-bistrifluoromethylbenzoyl derivative of N τ-methylimidazoleacetic acid and electron capture negative ion chemical ionisation mass spectrometry. The derivative has very good chromatographic properties and a negative ion mass spectrum which contains only a molecular ion at m/z 422. When this ion is specifically monitored, an amount of derivative equivalent to 1 pg of parent compound can be detected. A deuterated analogue of N τ-methylimidazoleacetic acid was synthesised for use as an internal standard and this allowed the development of an assay for N τ-methylimidazoleacetic acid, in urine with a precision of 2.9% and in plasma with a precision of 1.5%.

Capillary Gas Chromatography/Positive and Negative Ion Chemical Ionization Mass Spectrometry on Pyrrolizidine Alkaloids of Senecio inaequidens Using Ammonia and Hydroxyl Ions as the Reagent Species

Capillary Gas Chromatography/Positive and Negative Ion Chemical Ionization Mass Spectrometry on Pyrrolizidine Alkaloids of Senecio inaequidens Using Ammonia and Hydroxyl Ions as the Reagent Species

Negative ion chemical ionization mass spectrometry—binding of molecules to bromide and iodide anions

AbstractThe analytical potential of negative ion chemical ionization (NICI) mass spectrometry utilizing dibromodifluoro‐methane (CF2Br2) and iodomethane (CH3I)/methane (CH4) as reagent gases is examined. The NICI mass spectrum of CF2Br2 contains Br−, [HBr2]− and [CF2Br3]− anions. Weak acids (i.e. those acids with approximately ΔH°(acid) values between 1674 and 1464 kJ mol−1) react with Br− to produce minor yields of the hydrogen−bonded bromide attachment [MH + Br]− anion or are unreactive. Strong acids (i.e. those acids with approximately ΔH°(acid) > 1464 kJ mol−1) produce primarily [MH + Br]− anions with a minor yield of proton transfer [M  H]− anion. The NICI spectrum of CH3I/CH4 is dominated by I−. Weak acids react with I− to yield minor amounts of [MH + 1]− or are unreactive. Strong acids produce only [MH + l]− anions. From a consideration of the gas‐phase basicity of the halide anion and the binding energy of the hydrogen‐bonded halide attachment adduct, thermochemical data are used as a potential guide to rationalize or predict the ions observed in NICI mass spectra.

Identification of nitrated polycyclic hydrocarbons in diesel particulate extracts by negative ion chemical ionization and tandem mass spectrometry

Solid phase extraction is used to clean-up diesel particulate extracts for an identification of nitrated polycyclic hydrocarbons (nitro-PAHs). Thirty eight nitro-PAHs were identified both by electron impact mass spectrometry at medium resolution (M/δM=5000), by negative ion chemical ionization (NICI) at medium resolution (M/δM=5000) under selected ion monitoring (SIM) conditions and by tandem mass spectrometry. A substantial increase in selectivity is achieved if tandem mass spectrometry is employed leading to an enhancement of the signal to noise ratio and to a more reliable compound assignment.

Studies on steroids

A method for the determination of 3 alpha,7 alpha-dihydroxy-5 beta-cholestanoic acid (DHCA) and 3 alpha,7 alpha,12 alpha-trihydroxy-5 beta-cholestanoic acid (THCA) in human urine by gas chromatography (GC) in combination with negative ion chemical ionization (NICI) mass spectrometry is described. Unconjugated, glycine- and taurine-conjugated DHCA and THCA labelled with 18O and 2H were used as internal standards. 5 beta-Cholestanoic acids in urine were extracted with a Sep-Pak C18 cartridge, separated into the unconjugated, glycine- and taurine-conjugated fractions by ion-exchange chromatography on piperidinohydroxypropyl Sephadex LH-20 and, following alkaline hydrolysis of conjugated forms, derivatization into the pentafluorobenzyl ester-dimethylethylsilyl ethers. Subsequent resolution of each fraction into DHCA and THCA was attained by GC on a cross-linked 5% phenylmethylsilicone fused-silica capillary column where 5 beta-cholestanoic acids were monitored with a characteristic carboxylate anion [M-181]- in the NICI mode using isobutane as a reagent gas. The method was applied to separation and determination of 5 beta-cholestanoic acids in urine from a patient with Zellweger syndrome and from healthy volunteers.

Pentafluorobenzoic anhydride as a derivatizing agent for alcohols and hydroxy fatty acid methyl esters detected by electron capture in gas chromatography

Pentafluorobenzoate derivatives of primary and secondary alcohols have been prepared using pentafluorobenzoic anhydride. The gas chromatographic properties of the homologous series of the methyl esters of 2-hydroxycarboxylic acids from C 12 to C 26 have been studied on the high-temperature stationary phase Poly-S 179. The suitability of determining trace amounts of these compounds using gas chromatography with an electron-capture detector and with electron-capture negative-ion chemical-ionization mass spectrometry is discussed.

Quantitative measurement of clonidine in human plasma by combined gas chromatography/electron capture negative ion chemical ionization mass spectrometry.

A new quantitative and selective assay was developed for the measurement of low levels of clonidine in human plasma. The drug and the deuterated internal standard (2H4)clonidine are quantified by gas chromatography/negative ion chemical ionization mass spectrometry with methane as the reagent gas. After a three-step extraction procedure, the two compounds of interest are converted to their fluorinated derivatives using 3,5-bis(trifluoromethyl)benzoyl chloride. The mass spectrometer is focused to monitor abundant and stable characteristic high-mass ions (m/z 673 and 709) which are generated in the ion source by a resonance electron capture process. This assay requires only 1 ml of plasma sample and the limit of detection of the method is 5 pg ml-1 with a relative standard deviation of less than 7%.

Gas‐phase reactions of electrons, halide ions and radicals with (meso‐tetraphenylporphinato)metal(II) complexes under negative ion chemical ionization conditions

AbstractThe negative ion chemical ionization mass spectra of a series of (meso‐tetraphenylporphinato)metal(II) (metal = Mg, Co, Ni, Cu, Zn) complexes obtained with the electron‐energy‐moderating/reagent gases argon, NF3, CF2Cl2 and CF3Br are presented. Formation of the negative ions identified in the mass spectra is accounted for in terms of the chemistry which occurs in the gaseous plasmas. In argon plasmas, the metal complexes undergo resonance electron capture with comparable facility to produce stable molecular ions. In the NF3, CF2Cl2 and CF3Br plasmas, ionization occurs as a result of ion–molecule reactions as well as resonance electron capture, and is quite selective. Only fluoride ions react with each of the metal complexes, producing metal‐containing ions by nucleophilic addition and proton abstraction as well as by inducing ring closure. The less reactive chloride and bromide ions react readily by nucleophilic addition only with the magnesium and zinc complexes. Negative ions are also produced in the plasmas by radical‐molecule reactions followed by ionization of the neutral products of these encounters.

An assay for 2-amino-3,8-dimethylimidazo[4,5-f]-quinoxaline and 2-amino-3,4,8-trimethylimidazo-[4,5-f]quinoxaline in fried beef using capillary column gas chromatography electron capture negative ion chemical ionization 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 ionization mass spectrometry and a stable isotope labelled analogue of MeIQx 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-1 meat, 1.2 ng DiMeIQx g-1 meat; patty 2:1.3 ng MeIQx g-1 meat, 0.5 ng DiMeIQx g-1 meat). Neither compound was present in the meat prior to cooking.

Methane chemical ionization mass spectrometry of the pentafluorobenzyl derivatives of abscisic acid, its metabolites and other plant growth regulators

Tetraethyl ammonium hydroxide has been used as a catalyst for the pentafluorobenzylation of abscissic acid and its metabolites, as well as zeatin, gibberellic acid and indole acetic acid. These derivatives, acetylated where necessary, were subjected to methane negative ion chemical ionization mass spectrometry. The spectra were quite simple and are therefore ideally suited for selected ion monitoring at high sensitivity with heavy isotope labelled internal standards. The sensitivity for pentafluorobenzyl abscisate was 20 fg with a signal to noise ratio of greater than 10:1. The other compounds were within an order of magnitude of this. It is thus feasible, at least in principle, to quantify components from all four groups of plant growth regulators from the same tissue.

Negative ion chemical ionization (Cl−) mass spectra of amino acids

Negative ion chemical ionization (Cl - ) mass spectra of the commonly occurring amino acids are simple and give information regarding molecular weight by the presence of [M + Cl] - adduct in the case of simple amino acids and [M - H] - in the case of amino acids containing additional polar groups. tert-Butyloxycarbonyl (BOC)-protected di - , tri - and tetrapeptides also given abundant [M + Cl] - ions.