Chemical Ionization Conditions Research Articles

Gas-Phase Alcoholysis of Benzylic Halides in the Atmospheric Pressure Ionization Source.

The present study investigates the gas-phase alcoholysis reaction of benzylic halides under atmospheric pressure chemical ionization (APCI) conditions. The APCI corona discharge is used to initiate the novel reaction, which is monitored by ion trap mass spectrometry (IT-MS). The model compound α,α,α-trifluorotoluene is applied to observe the cascade methoxylation reaction during the +APCI-MS analysis, resulting in the formation of [PhC(OCH3)2]+. Based on the results of isotopic labeling and substrate expansion experiments, an addition-elimination mechanism is proposed: initially, the reaction was initiated by the dissociation of fluorine from PhCF3 under APCI condition, leading to the formation of [PhCF2]+; subsequently, two methanol molecules nucleophilicly attack [PhCF2]+ stepwisely, accompanied by the elimination of HF, yielding the product ion [PhC(OCH3)2]+. The proposed mechanism was further corroborated by theoretical calculations. The results of substrate scope expansion experiments suggest that this in-source reaction has the potential to differentiate the positional isomers of alcohols and phenols.

Contact chemoreceptive mate recognition in Cerambyx welensii Küster (Coleoptera: Cerambycidae)

Abstract Cerambyx welensii Küster (Coleoptera: Cerambycidae) is a wood‐borer responsible for the decline of Mediterranean oaks in open woodlands. To establish that contact pheromones are involved in mate recognition of C. welensii, we extracted the cuticular hydrocarbons by solid phase microextraction at pre‐reproductive, beginning and ending of the reproductive period, and by solvent extraction of prothorax and elytra. The extracts were analysed by GC–MS under electron impact and chemical ionization conditions. Cuticular hydrocarbon profiles varied according to the reproductive period, although differences between sexes were not significant. Two compounds, 11/13‐methylheptacosane and 11‐methylnonacosane were more abundant in females at the beginning and ending of the reproductive periods. Compound 11/13‐methylheptacosane was also more representative in female prothorax than in males, and 2‐methyloctacosane was richer in male elytra than in females. We also studied the role of cuticular hydrocarbons in mate recognition in arena bioassays. Treatment of solvent‐washed dead females and glass dummies with one female equivalent (FE) of cuticular extract elicited mating responses in males, especially at the beginning of the reproductive period, with copulation attempts reaching 61.9% on solvent‐washed dead females and 23.8% on dummies. The successive treatment with synthetic compounds approaching a male cuticular profile inhibited male response. Our results confirm that contact pheromones mediate mate recognition in C. welensii. Knowledge of the precise role played by the major compounds 11/13‐methylheptacosane and 11‐methylnonacosane and other minor compounds representative in female prothorax may contribute to the development of novel management strategies against C. welensii.

Sustainable and Rapid Determination of Two Halogenated Pesticides in a Commercial Formulation by Solid Phase Microextraction and Liquid Phase Chemical Ionization Mass Spectrometry

This work presents a sustainable and rapid method for halogenated pesticide analysis without chromatographic separation. The system is composed of a microfluidic open interface (MOI) for solid-phase microextraction (SPME) liquid phase desorption, connected to a liquid electron ionization mass spectrometry interface (LEI-MS). Either a triple quadrupole mass spectrometer (QQQ-MS/MS, (low-resolution) or a quadrupole-time-of-flight tandem MS (QTOF-MS/MS, high-resolution) were employed, each operating in negative chemical ionization (NCI) conditions. The flow rate used (100 µL/min) to rapidly empty the MOI chamber (approximately 2.5 µL) is reduced to the working flow rate of the LEI interface (500 nL/min) by a passive flow splitter (PFS). NCI is an appropriate ionization technique for electrophilic compounds, increasing specificity and reducing background noise. Two halogenated pesticides, dicamba and tefluthrin, were extracted simultaneously from a commercial formulation matrix (CF) using a C18 fiber by direct immersion (3 min under vortex agitation). Analyte desorption occurred in static conditions inside MOI filled with acidified acetonitrile (ACN) (0.2% phosphoric acid, PA). Extraction and desorption steps were optimized to increase efficiency and accelerate the process. No chromatographic separation was involved; therefore, the system fully exploited MS/MS selectivity and HRMS accuracy demonstrating good linearity, repeatability and limits of detection (LODs) and limits of quantification (LOQs) in the pg/mL range (50 and 500 pg/mL, respectively). Low-resolution experiments showed that matrix effects (ME) did not affect the results. The fast workflow (5 min) makes the system suitable for high-throughput analysis observing the principles of green analytical chemistry (GAC).

Mass-spectra of new heterocycles: XXIV. Electron impact and chemical ionization study of <i>N</i>-[3-alkoxyand 3-(1<i>H</i>-pyrrol-1-yl)-2-thienyl]imidothiocarbamates

The behavior of a wide range of previously unknown N -(2-thienyl)imidothiocarbamates synthesized in a single preparative step from heterosubstituted allenes (methoxy-, 1-ethoxyethoxy- and 1 H -pyrrol-1-ylallenes) and aliphatic, cycloaliphatic, and aromatic isothiocyanates was studied under conditions of electron (70 eV) and chemical (reagent gas - methane) ionization. Under the electron impact, the studied compounds form an unstable molecular ion, the main direction of fragmentation of which is associated with the breaking of the C-N bond in the imidoformamide fragment with charge localization at the imine nitrogen atom. A similar decay channel of a molecular ion is also observed in the chemical ionization mass spectra of the studied compounds. In this case, characteristic, but low-intensity ions in the electron ionization spectra of N -(3-methoxy-2-thienyl)imidothiocarbamates become dominant in the chemical ionization spectra. In the chemical ionization spectra of N -[3-(1 H -pyrrol-1-yl)-2-thienyl]imidothiocarbamates, the maximum intensity peak belongs to the [ M - SMe]+ ion. For N -[3-(1-ethoxyethoxy)-2-thienyl]imidothiocarbamate, the peak of the ion formed upon successive elimination of ethoxyethene and methanethiol molecules from the [ M + H]+ ion has the maximum intensity.

Stochastic dynamic quantitative and 3D structural matrix assisted laser desorption/ionization mass spectrometric analyses of mixture of nucleosides

The paper tackles issue of solid-state 3D structural analysis by means of matrix assisted laser desorption/ionization mass spectrometry with a view of our innovative stochastic dynamic new simplistic formula D”SD = 2.6388.10−17.(<I2>–<I>2). It represents a universal law, which is obeyed by temporal behavior of experimental variable intensity of any analyte peak of ion, measured in solution under soft-ionization electrospray ionization, collision induced dissociation and atmospheric pressure chemical ionization conditions, respectively. The equation connects between so-called stochastic dynamic diffusion parameter, D”SD, and variable intensity, I, determined per any span of scan time of a measurement. So far, it has been proven empirically, that D”SD parameters of MS ions reflect exactly analyte concentration in solution — a claim independently verified via chromatography — and provide exact information about 3D molecular and electronic structure of molecular species in liquid phase. Herein, we urge that this simplistic formula is a fundamental law also valid to MALDI-MS phenomena; thus, providing exact quantitative and 3D molecular structural information about analytes in solid-state; or, mass spectrometric phenomena in condensed phases are governed by one and the same stochastic dynamic law, which is applicable both to quantitative and 3D analyses of analytes. The latter statement underlines a crucial advantage of the functional relation and emphasizes on incapability of other known fundamental MS theories and equation to deal with simultaneous exact quantitative and 3D structural analyses in the two condensed phases. A body of new empirical evidence is directed to favor the view of application of the model equation to MALDI-MS processes, examining guanosine (1) in mixture of N(2),N(2)-dimethyl guanosine, quantitatively and 3D structurally, with respect to different experimental conditions without, and involving different sample matrix components. The ultra-high accuracy mass spectrometric outcomes are treated by chemomerics. The same is true for utilizing high accuracy quantum chemical static and molecular dynamics in order to correlate experimental mass spectrometric with theoretical quantum chemical data on 3D molecular and electronic structures of nucleosides, their fragment species and energetics in gas and condensed phases. There are detailed subtle electronic effects on various tautomers, ionization processes, radical-ion formation MS reactions, chemical rearrangement, charge and (doubly) proton transfer effects; if any.

Mass Spectra of New Heterocycles: XXI. Study of Alkyl [(5-Amino-1H-pyrrol-2-yl)sulfanyl]acetates by Electron and Chemical Ionization Mass Spectrometry

The fragmentation of previously inaccessible alkyl [(5-amino-1H-pyrrol-2-yl)sulfanyl]acetates under electron (70 eV) and chemical (reactant gas methane) ionization conditions was studied for the first time. Under electron ionization, all the studied compounds form a molecular ion (Irel 7–100%), the main primary fragmentation pathway of which is associated with the C–S bond cleavage in the sulfanyl group and elimination of the ester fragment (R4OCOCH2) in the form of a radical. The chemical ionization of alkyl [(5-amino-1H-pyrrol-2-yl)sulfanyl]acetates is characterized by protonation, recharging, and electrophilic addition. The base peak belongs to an [M + H]+ ion. Chemical ionization is accompanied by the elimination of an R4OCOCH2 radical from the M+• and [M + Et]+ ions and an R4OCOCHS molecule from the M+• and [M + H]+ ions.

Mass Spectra of New Heterocycles: XX. Electron Impact and Chemical Ionization Mass Spectra of 5-(Prop-2-yn-1-ylsulfanyl)-1H-pyrrol-2-amines

Electron impact (70 eV) and chemical ionization (methane as reactant gas) mass spectra of 1-alkyl- and 1-[2-(vinyloxy)ethyl]-5-(prop-2-yn-1-ylsulfanyl)-1H-pyrrol-2-amines have been studied for the first time. The title compounds under electron impact form stable molecular ions which decompose mainly along pathways typical of the molecular ions derived from the corresponding intramolecular cyclization products, 7-alkyl- and 7-[2-(vinyloxy)ethyl]-2,7-dihydrothiopyrano[2,3-b]pyrrol-6-amines. In addition, fragment ions that could be formed only via decomposition of unrearranged molecular ion were detected. The main fragmentation pathway of their molecular ions involves cleavage of the N1-CAlk bond with the formation of stable [M − R3]+ ions (Irel 85–100%) {except for N,N-diethyl- and N,N-dipropyl-1-[2-(vinyloxy)emyl]-5-(prop-2-yn-1-ylsulfanyl)-1H-pyrrol-2-amines}. The results of quantum chemical calculations at the B3LYP/6-311+G(d,p) level of theory are consistent with the experimental data. In the chemical ionization mass spectra of 5-(prop-2-yn-1-ylsulfanyl)-1H-pyrrol-2-amines, the major peaks were those corresponding to M+· (Irel 65–100%) and [M + H]+ (Irel 75–100%). The title compounds have been found to undergo partial (5–10%) thermally induced isomerization to 5-(prop-1-yn-1-ylsulfanyl)-1H-pyrrol-2-amines under the chemical ionization conditions.

Gas chromatography/mass spectrometry analysis of reaction products of sulfur mustards with phenol.

Screening of chemicals related to chemical weapons convention including their all possible degradation and reaction products in environmental samples is important in the organization for prohibition of chemical weapons verification process. Sulfur mustards, commonly known as blistering agents, are included in schedule 1 chemicals of chemical weapons convention. Because of the presence of chlorine atoms in sulfur mustards, they are highly reactive and prone to react with other organic molecules such as phenols to produce corresponding reaction products. Thus, it is important to screen for not only the sulfur mustards but also their reaction products for verification process. The sulfur mustards and their degradation products have been routinely analyzed by gas chromatography/mass spectrometry method, however, the methods are yet to establish for the reaction products. In this study, the reaction products of the sulfur mustards with phenol (compounds 1-7) were studied by gas chromatography/mass spectrometry under electron ionization and chemical ionization conditions. The EI spectra of 1-7 displayed molecular ion and characteristic fragments that provided structure information. Mostly the fragment ions were due to homolytic cleavages involving C-O, C-S, and C-C cleavages. The methane or isobutane CI spectra showed M+., [M + H]+, and [M - H]+ ions including reagent specific adduct ions. The CI spectra also showed other adduct ions formed by association of analyte molecule with its most abundant fragment ion. The gas chromatography/retention index values were also calculated, which support unambiguous identification of targeted molecules in suspected environmental samples. The method was demonstrated for detection of the targeted molecules spiked in soil samples.

Mass Spectra of New Heterocycles. XVII. Main Fragmentation Routes of Molecular Ions of 4-Alkoxy-5-amino-3-methylthiophene-2-carbonitriles under Electron and Chemical Ionization

For the first time decomposition was investigated of 4-alkoxy-5-amino-3-methylthiophene-2-carbonitriles under the conditions of electronic (70 eV) and chemical (reagent gas methane) ionization. At the electronic ionization the compounds under study [except for 4-(1-ethoxyethoxy) and 4-(ferrocenylmethoxy) derivatives] form stable molecular ions that decompose mainly by the cleavage of an alkyl radical from the alkoxy-substituent. Further fragmentation of the arising ion [M–Alk]+ depends on the substituent nature in the amino group. In the mass spectrum of 4-(ferrocenylmethoxy)-substituted thiophene peaks of the ion [FcCH2]+ and its fragmentation products prevail. In the mass spectra of chemical ionization predominant peaks belong to ions M+·, [M + H]+ and [M + C2H5]+, and fragment ions are absent.

Modified proton transfer reaction mass spectrometry (PTR-MS) operating conditions for in vitro and in vivo analysis of wine aroma.

With proton transfer reaction-mass spectrometry standard operating conditions, analysis of alcoholic beverages is an analytical challenge. Ethanol reacts with the primary ion H3 O+ leading to its depletion and to formation of ethanol-related ions and clusters, resulting in unstable ionization and in significant fragmentation of analytes. Different methods were proposed but generally resulted in lowering the sensitivity and/or complicating the mass spectra. The aim of the present study was to propose a simple, sensitive, and reliable method with fragmentation as low as possible, linearity within a realistic range of volatile organic compounds concentrations, and applicability to in vivo dynamic aroma release (nosespace) studies of wines. For in vitro analyses, a reference flask containing a hydro-alcoholic solution (10% ethanol) was permanently connected to the PTR-MS inlet in order to establish ethanol chemical ionization conditions. A low electric field strength to number density ratio E/N (80 Td) was used in the drift-tube. A stable reagent ion distribution was obtained with the primary protonated ethanol ion C2 H5 OH2+ accounting for more than 80% of the ionized species. The ethanol dimer (C2 H5 OH)2 H+ accounted for only 10%. Fragmentation of some aroma molecules important for white wine flavor (various esters, linalool, cis-rose oxide, 2-methylpropan-1-ol, 3-methylbutan-1-ol, and 2-phenylethanol) was studied from same ethanol content solutions connected alternatively with the reference solution to the instrument inlet. Linear dynamic range and limit of detection (LOD) were determined for ethyl hexanoate. Fragmentation of the protonated analytes was limited to a few ions of low intensity, or to specific fragment ions with no further fragmentation. Association and/or ligand switching reactions from ethanol clusters were only significant for the primary alcohols. Interpretation of the mass spectra was straightforward with easy detection of diagnostic ions. These results made this ethanol ionization method suitable for direct headspace analyses of model wines and to their nosespace analyses.

Определение флупиртина в плазме крови методом ВЭЖХ с масс-спектрометрическим детектированием и его применение в фармакокинетических исследованиях

Предложен валидированный метод количественного определения флупиртина в плазме крови человека с использованием тандемной хроматомасс-спектрометрии (ВЭЖХ/МС/МС). Обработку биообразцов осуществляли методом осаждения белков метанолом. Хроматографическое разделение проводили на колонке Zorbax eclipse plus C18 в градиентном режиме элюирования. Для определения флупиртина использовали тройной квадрупольный масс-спектрометр Shimadzu 8040 в режиме детектирования заданных масс (+MRM) по основному молекулярному иону флупиртина m/z 305,2 в условиях химической ионизации при атмосферном давлении (APCI). Калибровочная кривая для флупиртина имела линейный характер (R = 0,994) в диапазоне концентраций 25 – 2500 нг/мл с нижним пределом чувствительности 25 нг/мл. Валидация метода свидетельствовала о его высокой чувствительности, специфичности, точности и воспроизводимости, а также о стабильности аналита. Метод успешно применен в сравнительном фармакокинетическом исследовании препаратов, содержащих флупиртин.

Analogues of primeval galaxies two billion years after the Big Bang

Deep observations are revealing a growing number of young galaxies in the first billion years of cosmic time1. Compared to typical galaxies at later times, they show more extreme emission-line properties2, higher star formation rates3, lower masses4, and smaller sizes5. However, their faintness precludes studies of their chemical abundances and ionization conditions, strongly limiting our understanding of the physics driving early galaxy build-up and metal enrichment. Here we study a rare population of ultraviolet-selected, low-luminosity galaxies at redshift 2.4 < z < 3.5 that exhibit all the rest-frame properties expected from primeval galaxies. These low-mass, highly compact systems are rapidly forming galaxies able to double their stellar mass in only a few tens of millions of years. They are characterized by very blue ultraviolet spectra with weak absorption features and bright nebular emission lines, which imply hard radiation fields from young hot massive stars6,7. Their highly ionized gas phase has strongly sub-solar carbon and oxygen abundances, with metallicities more than a factor of two lower than that found in typical galaxies of similar mass and star formation rate at z≤2.58. These young galaxies reveal an early and short stage in the assembly of their galactic structures and their chemical evolution, a vigorous phase that is likely to be dominated by the effects of gas-rich mergers, accretion of metal-poor gas and strong outflows. A selected group of intermediate-redshift galaxies appear similar to primeval galaxies. Analysing spectra of these nearer analogues for chemical abundances and ionization levels gives an improved understanding of galaxies that are too faint to study well.

Study on the accelerated Gutknecht self-cyclocondensation of amino-sugars under atmospheric pressure chemical ionization conditions

An unexpected catalyst-free gas phase Gutknecht self-cyclocondensation of d-glucosamine hydrochloride to 2,5-deoxyfructosazine under APCI conditions.

Gas-phase reactions of alcohols with hexamethylene triperoxide diamine (HMTD) under atmospheric pressure chemical ionization conditions.

Hexamethylene triperoxide diamine (HMTD) is a sensitive peroxide explosive first synthesized in 1885. HMTD exhibits an unusual gas-phase phenomenon in the presence of alcohols that has been previously observed, but incorrectly resolved. We are attempting to determine this specific mechanism. We used positive ion mode atmospheric pressure chemical ionization (APCI) as the interface to the mass spectrometer. HMTD was infused with various solvents including (18) O- and (2) H-labeled methanol in order to determine gas-phase reaction mechanisms. Based on these labeled experiments, it was determined that, under APCI conditions, the alcohol oxygen attacks a methylene carbon of HMTD and releases H2 O2 . This was attempted with nine different alcohols and, in each case, the alcohol is fully incorporated into the molecule with the peroxide release. A mechanism for this reaction has been proposed. This work appears to have confirmed the gas-phase reaction mechanism of HMTD with alcohols. As we continue efforts to characterize this unusual molecule, the information may prove useful in determining formation and degradation mechanism(s). In addition, this property of HMTD may find use in other fields of science.

Determination of triterpenoids from birch bark by liquid chromatography-tandem mass spectrometry

Pentacyclic triterpenoids from birch bark are of great interest as biologically active substances and raw materials for producing a wide range of drugs. In this work, a method for the highly sensitive determination of betulin, betulinic acid, lupeol, and erythrodiol in plant extracts based on a combination of high-performance liquid chromatography with tandem mass spectrometric detection is proposed. Mass spectra under the conditions of atmospheric pressure chemical ionization and collision-induced dissociation spectra of analytes are obtained. The conditions for mass spectrometric detection in the multiple reaction monitoring mode are optimized. The calculated detection limits are in the range 0.7–1.8 μg/L.

Mass spectrometry and quantum chemical studies of the reaction of divinyl telluride with secondary phosphine sulfides: Synthesis of adducts

Mass spectrometry and quantum chemical studies of the reaction of divinyl telluride with diphenylphosphine sulfide have been carried out. Reaction proceeds under radical initiation (AIBN, 63–68 °С, 2.5 h, THF, reactants molar ratio = 1:1) to afford the anti-Markovnikov monoadduct 1 and diadduct 2 in 67 and 23% yield, respectively. The former easily decomposes to give vinyldiphenylphosphine sulfide 3 (in 63% yield), ethylene and elemental tellurium, the structure of which represents mainly nano-sized powder consisting of agglomerates with average size of 350–450 nm. The comparative analysis of electron ionization mass spectra of compounds 1, 2 and 3 indicates that the presence of tellurium atom in adducts 1 and 2 reduces stability of their molecular ions and hinders the elimination of sulfur atom. Under conditions of chemical ionization of phosphine sulfides 1 and 3, the process of their protonation with CH5+ followed by the elimination of sulfur atom from [НМ]+ ion is dominant. These data are also confirmed by the results of quantum chemical calculations of the most stable protonated structures of phosphine sulfides 1 and 3.

Cyclic Acyloxonium Ions as Diagnostic Aids in the Characterization of Chloropropanol Esters under Electron Impact (EI), Electrospray Ionization (ESI), and Atmospheric Pressure Chemical Ionization (APCI) Conditions

During mass spectrometric analysis of various lipids and lipid derivatives such as the chlorinated counterparts of triacylglycerols, the detailed structure of the characteristic and common ions formed under electron impact (EI), electrospray ionization (ESI), and atmospheric pressure chemical ionization (APCI) conditions by the loss of a single fatty acid remains ambiguous. These ions are designated in the literature as "diacylglyceride ions" and are frequently depicted with a molecular formula without showing any structural features and sometimes represented as cyclic acyloxonium ions. Characterization of these ions is of considerable importance due to their utility in structural identification of lipid derivatives. This study provides complementary evidence on the cyclic nature of "diacylglyceride ions" through the use of the simplest 3-monochloropropanediol diester as a model and the use of isotope labeling technique. Tandem MS/MS studies have indicated that the ion at m/z 135.6 generated from 1,2-bis(acetoyl)-3-chloropropane through the loss of an acetyl group was identical to the ion at m/z 135.6 generated from 4-chloromethyl-2,2-dimethyl-1,3-dioxolane, the latter being generated from a cyclic precursor through the loss of a methyl radical, keeping the dioxolane ring structure intact, thus confirming the cyclic nature of these ions. The corresponding cyclic oxonium ions generated from longer chain chloropropanol diesters, such as the ion at m/z 331.2 originating from 3-monochloropropanediol (3-MCPD) diesters containing palmitic acid(s), could serve as chemical markers for the presence chloropropanol esters.

Mass spectral characterization of the CWC‐related isomeric dialkyl alkylphosphonothiolates/alkylphosphonothionates under gas chromatography/mass spectrometry conditions

The isomeric dialkyl alkylphosphonothiolates and dialkyl alkylphosphonothionates are listed as scheduled chemicals of the Chemical Weapons Convention (CWC) implemented by the OPCW. The P-S and P-R bond connectivity has to be correctly identified for the verification of the CWC. The present study demonstrates successful identification of the target isomers by selective fragmentation under electron ionization (EI) or chemical ionization (CI) conditions. All the studied isomeric compounds (27 in total) were synthesized in our laboratory using established methods, then analyzed by EI and CI gas chromatography/mass spectrometry (GC/MS) using an Agilent 6890 gas chromatograph equipped with a HP-5MS capillary column and interfaced to a 5973 N mass-selective detector. The retention index (RI) values of all the compounds were calculated using Van den Dool's formula. GC/MS/MS and GC/HRMS experiments were also performed using a VG-Autospec (magnetic sector) and JEOL-AccuToF (time-of-flight) mass spectrometer, respectively. The EI mass spectra of all the compounds had an abundant molecular ion at m/z 182, except in the case of a few selected butyl-substituted compounds, where this ion was of low abundance. The EI fragmentation pathways include α-cleavage, McLafferty rearrangement, McLafferty + 1 rearrangement, O/S-alkyl radical loss, and an alkene loss with a hydrogen shift. The characteristic fragment ions and their relative abundances are significant in elucidating the alkyl group attached to the P/S/O-atoms as well as the P-S/P = S bond connectivity. The EI and CI mass spectra together with RI values enable unambiguous identification of all the studied isomeric compounds. The present study highlights the structural characterization of the isomeric phosphonothiolates and phosphonothionates based on their selective EI fragmentation. The assigned fragmentation pathway helps in the assignment of P-S and P-alkyl connectivity in phosphonothiolates and phosphonothionates, consequently the structure of the unknown compounds. The EI mass spectra (27 compounds) of isomeric compounds are immensely useful in the OPCW official proficiency tests and for off-site analysis.

Homolytic Reactive Mass Spectrometry of Fullerenes: Peculiarities of the Reactions of C60 with Aromatic Compounds in the Ionization Chambers of Mass Spectrometers and in Solution

C60 reacted with PhH, PhCl, BnH, BnNH2, and o-C2H2B10H10 in the electron impact (EI) ion source of a mass spectrometer at 300 °C forming phenyl, benzyl, and o-carboranyl adducts, respectively, stabilized by hydrogen addition and loss. Besides, the additions to C60 of methyl and phenyl radicals for toluene, and a phenyl radical for benzylamine were observed. A homolytic reaction mechanism was suggested involving the reaction of the radicals formed from the aromatics under EI with C60 at the ionization chamber walls. While the ion/molecule reaction of C60 with benzene performed by Sun et al. under chemical ionization conditions at 200 °C afforded the complex C60•PhH(+•), quite a different isomer, HC60Ph(+•), was detected in the present study as a sequence of the different reaction mechanisms. C60 also reacted with benzyl bromide in the laser desorption/ionization (LDI) source of a mass spectrometer to give C60CPh(+). Phenyl and benzyl derivatives of C60 were found, respectively, when the reactions of the fullerene with PhCl, BnH, and BnBr were performed in solution under ultra violet irradiation. For the reaction with toluene, the strong chemically induced dynamic electron polarization of the intermediate benzylfullerenyl radical with the reverse phase effect was found. The coincidence of the results of the mass spectrometry and solution reactions of C60 with aromatics, even though incomplete, additionally supports the hypothesis, formulated earlier, that the former results can predict the latter ones to a significant extent and shows that this conclusion is valid for both EI and LDI initiated reactions in mass spectrometers.

LC–MS/MS bioanalytical method development for AMG 900: Resolution of an isobaric interference in rodent in vivo studies

AMG 900 is an orally available small molecule that is a highly potent and selective pan-aurora kinase inhibitor currently in development for the treatment of advanced human cancers. A co-eluting, isobaric interference was discovered in preliminary LC–MS/MS analyses of rodent in vivo pharmacokinetic samples during preclinical evaluation of AMG 900. The interference was identified as a major circulating N-oxide metabolite which partially converted to an [M+H−O]+ ion under the conditions of atmospheric pressure chemical ionization. A selective liquid chromatography–tandem mass spectrometry method for the simultaneous quantification of AMG 900 and its N-oxide metabolite in plasma was developed and successfully applied for the bioanalysis of discovery stage preclinical rodent pharmacokinetic studies.