Surface-activated chemical ionization ion trap mass spectrometry in the analysis of amphetamines in diluted urine samples

A new ionization method, named surface-activated chemical ionization (SACI), was employed for the analysis of five amphetamines (3,4-methylenedioxyamphetamine (MDA), 3,4-methylenedioxymethamphetamine (MDMA), 3,4-methylenedioxyethylamphetamine (MDE), amphetamine and methamphetamine) by ion trap mass spectrometry. The results so obtained have been compared with those achieved by using atmospheric pressure chemical ionization (APCI) and electrospray ionization (ESI) using the same instrument, clearly showing that SACI is the most sensitive of the three. The limit of detection and linearity range for SACI were compared with those obtained using APCI and ESI, showing that the new SACI approach provides the best results for both criteria. SACI was used to analyze MDA, MDMA MDE, amphetamine and methamphetamine in four urine samples, and the quantitation results are compared with those achieved using ESI.     

Low pressure chemical ionization in ion trap mass spectrometry

This article presents the specificities of low pressure chemical ionization in ion trap mass spectrometry. One main feature is the ability to perform chemical ionization with liquid reagents as readily as with "conventional" gases (methane, isobutane and ammonia). The reactivities and analytical applications of gas and liquid reagents are summarized from literature data and are compared when possible.     

Surface-activated chemical ionization ion trap mass spectrometry in the analysis of drugs in dilute urine samples. Part II: analysis of morphine and other street drugs

The new ionization method, called surface-activated chemical ionization (SACI), was employed for the analysis of fives drugs (morphine, codeine, 6-monoacetylmorphine (6-MAM), benzoylecgonine and cocaine) by ion trap mass spectrometry. The results so obtained have been compared with those achieved by using atmospheric pressure chemical ionization (APCI), no-discharge-APCI and electrospray ionization (ESI) clearly showing that SACI is the most sensible one mainly due to the high ionization efficiency and the lower chemical noise. The performance of SACI in terms of sensitivity and linearity was compared with the sensitivity and linearity obtained using APCI, no-discharge-APCI and ESI, showing that the new SACI approach gives rise to the best results. Then, SACI was used to analyze morphine, codeine, 6-MAM, benzoylecgonine and cocaine in urine samples. After the optimization of the instrumental parameters for a mixture of the standard compounds, eight urine samples were analyzed. They were strongly diluted (1 : 20 and 1 : 100) in order to prevent the chromatographic column damage due to the matrix composition. Furthermore, the diluted urine samples were directly analyzed, without pretreatment, through LC-MS and LC-MS/MS, and the obtained results are reported.     

Mass-selected reagent ion chemical ionization and multiple tandem mass spectrometry techniques in an ion trap mass spectrometer for structural analysis

Mass-selected reagent ion chemical ionization (CI) performed in an ion trap instrument is an efficient tool to investigate gas-phase ion reactivities and therefore to find out new and/or optimized applications for structural analysis. For instance, it was shown that the C₃H₆O^{+ .} (58 mass units) molecular ion originated from vinyl methyl ether (VME) should necessarily be used alone (i.e. unit-mass selected) to produce significant diagnostic-ions for double bond location in aliphatic alkenes. Regarding the assignment of epoxides, the previous NO⁺/CI method was adapted for an optimal use in the trap through isolation of NO⁺ cation from N₂O (instead of NO) plasma and production of the acylium diagnostic-ions via CID of [M − H]⁺ formed by NO⁺-induced hydride abstraction. New alkylation ion-products, e.g. RCH = O⁺-al , were also found to characterize isomeric epoxides as a result of either an initial electrophilic addition of the C₂H₅⁺ cation (with saturated epoxides) or a methyl-transfer from [VME]^{+ .} (with α,β-unsaturated epoxides). The multiple tandem mass spectrometry (MSⁿ) capabilities of the ion trap were essential to achieve reagent ion mass-selection, structural assignment of the diagnostic-ions, or to provide further selectivity. © 1997 John Wiley & Sons, Ltd.     

Laser desorption lamp ionization source for ion trap mass spectrometry

A two‐step laser desorption lamp ionization source coupled to an ion trap mass spectrometer (LDLI‐ITMS) has been constructed and characterized. The pulsed infrared (IR) output of an Nd:YAG laser (1064 nm) is directed to a target inside a chamber evacuated to ~15 Pa causing desorption of molecules from the target's surface. The desorbed molecules are ionized by a vacuum ultraviolet (VUV) lamp (filled with xenon, major wavelength at 148 nm). The resulting ions are stored and detected in a three‐dimensional quadrupole ion trap modified from a Finnigan Mat LCQ mass spectrometer operated at a pressure of ≥ 0.004 Pa. The limit of detection for desorbed coronene molecules is 1.5 pmol, which is about two orders of magnitude more sensitive than laser desorption laser ionization mass spectrometry using a fluorine excimer laser (157 nm) as the ionization source. The mass spectrum of four standard aromatic compounds (pyrene, coronene, rubrene and 1,4,8,11,15,18,22,25‐octabutoxy‐29H,31H‐phthalocyanine (OPC)) shows that parent ions dominate. By increasing the infrared laser power, this instrument is capable of detecting inorganic compounds. Copyright © 2015 John Wiley & Sons, Ltd.     

Enhanced signal generation for use in the analysis of synthetic pyrethroids using chemical ionization tandem quadrupole ion trap mass spectrometry

Synthetic pyrethroids fragment extensively under electron ionization (EI) conditions to give low mass ions, most of them with the same m/z ratios. This fragmentation is primarily due to the labile ester linkage found in these compounds. In this research we established the best gas chromatography (GC) conditions in the EI mode that served as a benchmark in the development of a chemical ionization (CI) protocol for ten selected synthetic pyrethroids. Based on proton affinity data, several reagent gases were evaluated in the positive CI ionization mode. Methanol was found to produce higher average ion counts relative to the other gases evaluated, which led to the development of an optimized method consisting of selective ejection chemical ionization (SECI) and MS/MS. Standard stainless steel ion trap electrodes produced significant degradation of chromatographic performance on late eluting compounds, which was attributed to electrode surface chemistry. A dramatic improvement in signal-to-noise (S/N) ratios was observed when the chromatographically inert Silcosteel® coated electrodes were used. The resulting method, that has significant S/N ratio improvements resulting from a combination of septum programmable injections (SPI), optimized CI and inert Silcosteel®-coated electrodes, was used to determine instrument detection limits.     

Application of nonresonance excitation to ion trap tandem mass spectrometry and selected ejection chemical ionization

Nonresonance excitation is a universal ion excitation and ejection method in which increased ion kinetic energy is achieved by the combination of an axial dc dipole and the rf trapping fields. The method does not require the applied excitation frequency to match with the secular frequency of the precursor ions to effect collision-induced dissociation (CID) for tandem mass spectrometry applications. Therefore, it is free of the effects of secular frequency changes caused by space-charge and simplifies the optimization of tandem mass spectrometry parameters when combined with gas chromatography-tandem mass spectrometry (GC-MS/MS). Computer simulations show that in contrast to the resonance excitation process, the nonresonance excitation process is able to accelerate thermal ions to kinetic energies in excess of 40 eV in a few microseconds. Based on simulations, we expect that the rapid deposition of energy by this method may allow the study, in ion traps, of high energy decomposition channels of precursor ions with multiple decomposition channels. Furthermore, the method is able to simultaneously excite multiple precursor ions, for example, excite both analyte and its coeluting isotopically labeled internal standard for GC-MS/MS analysis. A GC-MS/MS analysis of 100 pg of n-butylbenzene is demonstrated with a signal-to-noise ratio of 3624, which is over an order of magnitude higher than the signal-to-noise ratio of 345 obtained by full scan gas chromatography-mass spectrometry. In addition, the nonresonance excitation method can be used as a low pass mass filter in the chemical ionization (CI) mode to eject undesired fragment ions that result from direct electron ionization. This new CI method, selected ejection chemical ionization, can produce a CI spectrum without contamination of sample fragment ions from electron ionization.     

Selective chemical ionization of nitrogen and sulfur heterocycles in petroleum fractions by ion trap mass spectrometry

A procedure is reported for the selective ammonia chemical ionization of some nitrogen and sulfur heterocycles in petroleum fractions using ion trap mass spectrometry (ITMS). The ion trap scan routine is designed to optimize the population of ammonium reagent ions and eject from the trap (by radio frequency/direct current isolation) electron ionization products formed during reagent ion formation prior to ionization of the sample. The ITMS procedure is compared with standard ion trap detector and conventional quadrupole ammonia chemical ionization for the determination of nitrogen and sulfur heterocycles in gas oil and kerosine samples. Greatly enhanced selectivity is shown for the ITMS procedure by suppression of competing charge-exchange processes.     

Selective adduct formation by furan chemical ionization reagent in gas chromatography ion trap mass spectrometry

The analytical potential of furan as a chemical ionization (CI) reagent was evaluated for selectivity with nine monosubstituted naphthalene compounds. The ion-molecule reactions of furan and tetrahydrofuran (THF) were compared with those of methane, methanol and acetonitrile (prominently producing [M + H](+) ion base peaks) with naphthalene compounds in chemical ionization mass spectrometry (CI-MS). Reactions with furan predominantly show M(+) and [M + 39](+) ions. Based on this phenomenon, investigations were carried out for some of the molecular factors such as proton affinity, substituent effects and the preferred site of [C(3)H(3)](+) ion attachment that influence reactivity in furan CI. High selectivity with different substituents is observed in the formation of [M + 39](+) adduct ion, suggesting its usefulness as selective ionization reagent liquid. The selectivity and sensitivity are illustrated in the analysis of mixture of amino acids. Furthermore, the structure determination and reaction mechanism study is characterized by collision-activated dissociation experiments in CI-MS/MS and CI-MS/MS/MS.     

Negative chemical ionization in quadrupole ion trap mass spectrometry: Effects of applied voltages and reaction times

The effects of applied voltages and reaction times on negative ion chemical ionization in the quadrupole ion trap are investigated. Mass-selected ejection of undesired reagent ions and selective mass storage of only negative ions are required for practical negative ion chemical ionization. This is achieved by application of rf and dc voltages to the ring electrode to control the mass-to-charge ratios one polarity) of ions stored, as well as by application of a supplemental rf voltage applied across the endcap electrodes to selectively eject ions of a particular mass-to-charge ratio. Even with careful control of these parameters, negative chemical ionization is not as sensitive as electron ionization and positive chemical ionization because of the lack of thermal electrons in the ion trap. Mass selection of the hydroxide anion as a reagent ion and exclusion of all positive ions provide [M ? H]^? ions with little or no fragmentation for a wide variety of compounds.     

High-throughput chemical residue analysis by fast extraction and dilution flow injection mass spectrometry

Fast extraction and dilution flow injection mass spectrometry (FED-FI-MS) is presented as a technique to increase throughput in quantitative multiresidue screening in complex matrices, while meeting current analytical method quality requirements.     

Electrospray ionization tandem mass spectrometry for the simultaneous determination of opiates and cocaine in human hair

A fast and highly sensitive electrospray ionization tandem mass spectrometry (ESI-MS/MS) method has been developed for the simultaneous determination of morphine, 6-methylacetylmorphine (6-MAM), codeine, cocaine and benzoylecgonine (BZE) in hair from drug abusers. Pulverized hair samples were subjected to an optimized matrix solid phase dispersion (MSPD) procedure with alumina, followed by diluted hydrochloric acid elution on column solid-phase extraction (SPE) clean-up/pre-concentration. Alternatively, samples were also subjected to an optimized ultrasound assisted enzymatic hydrolysis (USEH) with Pronase E, followed by an off-line SPE clean up/pre-concentration procedure. Positive electrospray ionization and multiple reaction monitoring (MRM) with one precursor ion/product ion transition were used for the identification and quantification (deuterated analogues of each target as internal standards) of each analyte. The chromatographic pump and the autosampler were used for injecting the standards and the hair extracts (20 μL) as a flow injection analysis mode. The highest sensitivity was achieved when delivering the targets with an acetonitrile/water/formic acid (80/19.875/0.125) mixture. The limits of detection of the method were 39.2, 4.4, 6.8, 7.0 and 7.4 ng g(-1) for morphine, 6-MAM, codeine, cocaine and BZE, respectively. Relative standard deviations of intra- and inter-day precision were lower than 9 and 12%, respectively; whereas, analytical recoveries ranged from 96±5 to 106±4%. The developed method (MSPD-ESI-MS/MS) was applied to different hair samples from polydrug abusers, and results were statistically compared to those obtained after a conventional gas chromatography-mass spectrometry (GC-MS) analysis and also after USEH and ESI-MS/MS or GC-MS determinations.     

Negative ion chemical ionization mass spectrometry of some isocyanates

Summary Negative ion mass spectra for 3 aliphatic and 4 aromatic isocyanates have been obtained by low pressure chemical ionization, using CH₄, CO₂ and N₂O as reagent gases. All compounds furnished intense anions at m/z 42. With CH₄, quasi-molecular anions were observed at m/z M+1 for aliphatic and m/z M+1 and M–1 for aromatic isocyanates. With N₂O, anionic substitution products at m/z M+15 and M+30 were observed, and with CO₂ and N₂O, peaks at m/z M–12 could be detected for all aromatic isocyanates. Studies with ¹³CO₂ and C¹⁸O₂ as reagent gases showed that the anions at m/z M–12 and M+15 correspond to [M–CO+O]^– and [M–H+O]^–, respectively.

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Negativionen-Massenspektrometrie mit chemischer Ionisierung von einigen Isocyanaten

Zusammenfassung Die Negativionen-Massenspektren von 3 aliphatischen und 4 aromatischen Isocyanaten wurden mittels chemischer Ionisation bei tiefem Quellendruck aufgenommen, und zwar mit den Reagensgasen CH₄, CO₄ und N₂O. Alle Verbindungen lieferten intensive Anionen mit m/z 42. Mit CH₄ erhielten wir die quasi-molekularen Anionen M+1 für aliphatische sowie M+1 und M–1 für aromatische Isocyanate. Das Reagens N₂O ergab die anionischen Substitutionsprodukte M+15 und M+30. Sowohl CO₂ als auch N₂O führten mit aromatischen Isocyanaten zur Bildung von M–12 Anionen. Versuche mit ¹³CO₂ und mit C¹⁸O₂ als Reagensgase zeigten, daß die Anionen M–12 und M+15 den Ionen [M–CO+O]^– und [M–H+O]^– entsprechen.

     

Surface-activated chemical ionization combined with electrospray ionization and mass spectrometry for the analysis of cannabinoids in biological samples. Part I: analysis of 11-nor-9-carboxytetrahydro-cannabinol

Recently, electrospray ionization mass spectroscopy (ESI-MS) has been widely used for the identification of drugs of abuse and their metabolites in biological samples. However, the sensitivity and selectivity of this technique are commonly inadequate for the analysis of tetrahydrocannabinol (THC) and its metabolites at very low levels, such as those sometimes required in forensic and clinical-legal applications. We coupled electrospray ionization and surface-activated chemical ionization (ESI-SACI) to various types of mass analyzers (ion trap, triple quadrupole and orbitrap) (ESI-SACI-MS) to improve the detection of 11-nor-9-carboxy-tetrahydrocannabinol (THC-COOH), the most common marker of THC abuse. The benefits of this approach in terms of sensitivity and selectivity compared with a common ESI-MS approach are clearly demonstrated.     

Determination of 3-methyl-2,4-nonanedione in red wines using methanol chemical ionization ion trap mass spectrometry

A compound associated with oxidized flavor in red wines was recently-identified as 3-methyl-2,4-nonanedione (MND). In order to quantify it, positive chemical ionization (PCI) in an ion trap was studied using conventional liquid reagents such as methanol, acetonitrile, and acetone, as well as non-conventional liquid reagents such as ethyl acetate, diethyl ether, pentane, isohexane, and heptane. Under laboratory conditions, very different response factors were obtained with MND depending on the gas. We also compared the detection limit of conventional CI with hybrid chemical ionization (HCI). Finally, this compound was quantified in red wines by liquid/liquid extraction without any derivatization steps, followed by GC/MS-CI analysis, using methanol as the reagent gas. Coelutions of compounds with the same m/z were checked using methanol-d(4). The method we developed was linear in the 10-300 ng/L range of MND concentrations, with satisfactory repeatability. The detection limit was 4.3 ng/L, over 3 times lower than the olfactory perception threshold of this compound (16 ng/L). The suitability of this method for assaying this diketone in red wine was demonstrated by the analyzing many wines from different vintages.     

Atmospheric pressure chemical ionization of fluorinated phenols in atmospheric pressure chemical ionization mass spectrometry, tandem mass spectrometry, and ion mobility spectrometry

Atmospheric pressure chemical ionization (APCI)-mass spectrometry (MS) for fluorinated phenols (C6H5-xFxOH Where x = 0-5) in nitrogen with Cl- as the reagent ion yielded product ions of M Cl- through ion associations or (M-H)- through proton abstractions. Proton abstraction was controllable by potentials on the orifice and first lens, suggesting that some proton abstraction occurs through collision induced dissociation (CID) in the interface region. This was proven using CID of adduct ions (M Cl-) with Q2 studies where adduct ions were dissociated to Cl- or proton abstracted to (M-H)-. The extent of proton abstraction depended upon ion energy and structure in order of calculated acidities: pentafluorophenol > tetrafluorophenol > trifluorophenol > difluorophenol. Little or no proton abstraction occurred for fluorophenol, phenol, or benzyl alcohol analogs. Ion mobility spectrometry was used to determine if proton abstraction reactions passed through an adduct intermediate with thermalized ions and mobility spectra for all chemicals were obtained from 25 to 200 degrees C. Proton abstraction from M Cl- was not observed at any temperature for phenol, monofluorophenol, or difluorophenol. Mobility spectra for trifluorophenol revealed the kinetic transformations to (M-H)- either from M Cl- or from M2 Cl- directly. Proton abstraction was the predominant reaction for tetra- and penta-fluorophenols. Consequently, the evidence suggests that proton abstraction occurs from an adduct ion where the reaction barrier is reduced with increasing acidity of the O-H bond in C6H5-xFxOH.     

Surface-activated chemical ionization in the analysis of arginine in plasma samples

Alterations of arginine plasma levels are involved in several disorders of amino acid metabolism such as hurtnup, argininosuccinic aciduria, histidinemia, citrullinuria, and cystinuria. In this work a new liquid ionization source, surface-activated chemical ionization (SACI), has been used to analyze arginine in human and rat plasma samples. Arginine was extracted and diluted ten times through protein precipitation. The diluted arginine samples were then analyzed using an ion-exchange chromatographic column coupled with the SACI source and an ion trap analyzer using MS(3) monitoring in order to increase the sensitivity and specificity of the analysis. The multiple-point standard additions method was used to quantify the arginine. This method was employed to eliminate the matrix effect that affects all liquid ionization sources (APCI, ESI, SACI, etc.), and also does not require use of an internal standard. High-quality results in terms of sensitivity, limit of detection, lower limit of quantitation, linearity and reproducibility, are demonstrated.     

液相色谱-大气压化学电离离子阱质谱法测定烟草中的游离茄尼醇

用液相色谱/大气压化学电离离子阱质谱建立了一种分析烟草中游离茄尼醇的方法。烟草样品用甲醇振荡提取30 min,在分析前无需进行其它前处理。在1.8μm快速分离C18色谱短柱上用V(甲醇)∶V(异丙醇)=85∶15等梯度洗脱实现了茄尼醇的快速分离。用不带碰撞能量的二级质谱全扫描选择监测离子m/z 613.6进行定量,检出限为0.4μg/L,RSD为1.1%,两种添加量的回收率分别为97%和99%。方法应用于不同烟草和烟草制品样品的检测分析。