Pressure Ionization Tandem Mass Spectrometry Research Articles

Products of the gas-phase reactions of cis-3-hexen-1-ol with OH radicals and O 3

Products of the gas-phase reactions of OH radicals (in the presence of NO) and O 3 with the biogenic emission cis-3-hexen-1-ol have been investigated using gas chromatography with flame ionization detection (GC-FID), combined gas chromatography-mass spectrometry (GC-MS), gas chromatography with Fourier transform infrared spectroscopy (GC-FTIR), and direct air sampling, atmospheric pressure ionization tandem mass spectrometry (API-MS). Propanal and 3-hydroxypropanal were identified and quantified from the OH radical and O 3 radical reactions, with respective formation yields of 0.746 ± 0.067 and 0.48 −0.24 +0.48 from the OH radical reaction and 0.493 ± 0.075 and 0.33 −0.16 +0.33 from the O 3 reaction. In addition, a hydroxynitrate of molecular weight 179 [CH 3CH 2CH(OH)CH(ONO 2)CH 2CH 2OH and/or CH 3CH 2CH(ONO 2)CH(OH)CH 2CH 2OH] and a hydroxycarbonyl of molecular weight 132, expected to be CH 3CH 2CH(OH)CH(OH)CH 2CHO, were observed from the OH radical reaction by API-MS analyses. The reaction mechanisms are discussed.

Pharmacokinetic screening for the selection of new drug discovery candidates is greatly enhanced through the use of liquid chromatography–atmospheric pressure ionization tandem mass spectrometry

Selection of a new drug discovery candidate from a series of compounds requires a means of performing rapid analytical method development and sensitive quantitation of each drug in serum, plasma or other biological matrices. Information on serum/plasma concentration, bioavailability and half-life can often aid the discovery process by selecting those candidates with the desired pharmacokinetic parameters. In one series of farnesyl protein transferase (FPT) inhibitors, gas chromatography with nitrogen–phosphorus detection (NPD) was initially used to analyze samples from pharmacokinetic studies in mice and monkeys. Typical turnaround times using this technique approached 2–4 weeks for method development, quantitation of study samples and calculation of pharmacokinetic parameters. Once LC–atmospheric pressure ionization (API) MS–MS analysis was implemented in these same studies, they could be completed in less than one week. The advantages of using LC–API-MS–MS to aid in the drug candidate selection process is demonstrated for one compound (SCH 44342) in this series of FPT inhibitors.

Direct Identification of Phenolic Glucosides from Olive Leaf Extracts by Atmospheric Pressure Ionization Tandem Mass Spectrometry

Pneumatically assisted electrospray (or ionspray) coupled with liquid chromatography was applied to the identification of the phenolic glucoside content of olive leaf directly from the crude extracts. The mass spectra of the positive ions provide insights into the composition of the phenolic constituents. Oleuropein, ligstroside and a disaccharide containing the hydroxytyrosol moiety were found in olive leaf of Olea europea L. cv. Cassanese and their structures were thoroughly determined by tandem mass spectrometry. © 1977 by John Wiley & Sons, Ltd.

Direct Identification of Phenolic Glucosides from Olive Leaf Extracts by Atmospheric Pressure Ionization Tandem Mass Spectrometry

Direct Identification of Phenolic Glucosides from Olive Leaf Extracts by Atmospheric Pressure Ionization Tandem Mass Spectrometry

Chiral bioanalysis by normal phase high-performance liquid chromatography-atmospheric pressure ionization tandem mass spectrometry

A highly sensitive and specific chiral high-performance liquid chromatographic tandem mass spectrometric (HPLC-MS-MS) technique has been developed for the determination of several chiral drugs and their metabolites. Examples include enantiomers of verapamil and its most abundant active metabolite, norverapamil, enantiomers of oxybutynin and its metabolite, N-desethyloxybutynin, enantiomers of doxazosin and those of sotalol. These drugs are marketed as racemates although their optical isomers possess different pharmacological activities. Drug enantiomers and their respective chiral metabolites were separated by isocratic normal-phase chiral chromatography on a small-bore (100 × 2.1 mm I.D.) Chiralpak AD column. Post-column reagent addition of an aqueous mobile phase was introduced to enable direct coupling of hexane-based mobile phases chiral chromatography with the heated nebulizer interface of the SCIEX API 300 tandem mass spectrometer. Quantification of individual drug and metabolite enantiomers was obtained by multiple reaction monitoring. This novel approach was developed and used in bioanalytical studies. It successfully combines the convenience of normal-phase chiral separations on small-bore HPLC columns with high specificity and low limits of quantification achieved by atmospheric pressure ionization MS-MS detection.

Matrix‐related Modification of Ionization in Bioanalytical Liquid Chromatography‐Atmospheric Pressure Ionization Tandem Mass Spectrometry*

Matrix-related modification of ionization (collectively termed matrix effect) is a major area of concern in the development and validation of bioanalytical liquid chromatography-atmospheric pressure ionization tandem mass spectrometry (LC-API-MS/MS) assays. Matrix effects can be eliminated by a range of different methods including strategic choice of internal standard, enhanced sample clean-up, modification of chromatographic conditions, change of ionization technique and a reduction in injection volume.

Possible etiologic agents for toxic oil syndrome: Fatty acid esters of 3-(N-phenylamino)-1,2-propanediol

The etiologic agent(s) that was responsible for the 1981 toxic oil syndrome [TOS] epidemic in Spain has not been identified. Liquid chromatography combined with atmospheric pressure ionization tandem mass spectrometry was used for the analysis of oils associated with TOS. Analyses focused on measuring 3-(N-phenylamino)-1,2-propanediol [PAP], the 3-oleyl ester of PAP [MEPAP], and the 1,2-di-oleyl ester of PAP [DEPAP]. DEPAP and MEPAP were found more frequently and at higher concentrations in TOS case-associated oils than in control oils with odds ratios of 13.7 (95% CI 5.0-38) and 21.9 (95% 6.1-78), respectively. Other fatty acid esters of PAP are also likely to be present in the TOS case-associated oils. More significantly, DEPAP and MEPAP were found in aniline-denatured rapeseed oil refined at ITH, the oil refining company with the clearest link to TOS cases, yet these PAP esters were not detected in unrefined aniline-denatured samples of rapeseed oil delivered to ITH. These results show that the esters of PAP were products of the ITH refining process and were not formed spontaneously during storage. PAP esters were not detected in samples of other aniline-denatured rapeseed oils that were refined elsewhere, and which were not associated with illness. These findings provide strong support for the hypothesis that one or more of the fatty acid esters of PAP were the etiologic agents for TOS.

Collision‐induced dissociation studies of protonated alcohol and alcohol—water clusters by atmospheric pressure ionization tandem mass spectrometry. 1Methanol

AbstractCluster size distribution and collision‐induced dissociation (CID) studies of protonated methanol and protonated methanol—water clusters yield information on the structure and energetics of such ions. Ions were formed at atmospheric pressure in a corona discharge source, and were subjected to CID in the center quadrupole of a triple quadrupole mass spectrometer. Cluster ions containing up to 13 molecules of methanol and/or water were observed and examined using CID experiments. The CID of all (CH3OH)n · H2O · H+ clusters, where n ⩽ 8, showed that water loss was statistically favored over methanol loss and that the preferred dissociation channel involved loss of water with methanol molecules. These results support a model employing a chain of hydrogen‐bonded solvent molecules rather than one in which fused rings of ligands surround a central hydronium ion. However, CID of larger clusters, where n ⩾ 9, showed that loss of one methanol was equal to or less than loss of water, reflecting a change in structure.

Determination of collision‐induced dissociation mechanisms and cross‐sections in organophosphorus compounds by atmospheric pressure ionization tandem mass spectrometry

AbstractNineteen organophosphorus compounds (OPCs) of the generic classes (dialkyl alkyl′‐phosphonates (twelve compounds) and tri‐alkyl phosphates (seven compounds) were investigated by atmospheric pressure ionization (API) tandem mass spectrometry (MS/MS). All OPCs showed consistent and comparable collision‐induced dissociation (CID) pathways allowing for a generalized scheme for dissociation. When the alkyl groups are equal to or larger than ethyl, CID mechanisms are dominated by McLafferty rearrangements and neutral losses are stable molecules in all cases except cleavage of PC or OC bonds to form alkyl fragment ions. CID cross‐sections for the OPCs were determined with excellent reproducibility and a good correlation was found with a simple model. Inferences with respect to ionic structures were made from observed trends in the cross‐section measurements. Limitations in API‐MS/MS instruments of this design are found in the energy distribution of the ionization and ion sampling events.

Characterization of cyclotetramethylenetetranitramine (HMX) thermal degradation by isotope analyses with analytical pyrolysis‐atmospheric pressure ionization tandem mass spectrometry

AbstractAnalytical pyrolysis‐atmospberic pressure ionization (Py‐API) tandem mass Spectrometry was used in the structure elucidation of the oxidalive and non‐oxidative thermal decomposition products of cyclotetramethylenetetranitramine (HMX). The [15NO2]‐, [15N8]‐ and [2H8]‐HMX isotope preparations provided fundamental information in the determination of the identities of the various pyrolyzate species. All RDX pyrolysis product ions that were identified by Py‐API tandem mass Spectrometry, i.e. m/z 44, 60, 74, 75, 85 and 98, were present in the pyrolyzate of HMX. In both RDX and HMX investigations, these ions provided identical mass spectral daughter ion analyses. HMX, however, provided additional ions at m/z 30, 58, 69, 71, 83 and 141. Of all thirteen ions identified in the Py‐APJ mass spectrum of HMX, only that at m/z 75 contained a nitrogen atom that originated from the NO2 group. Standards analysis confirmed the identities of the ions at m/z 69, 71 and 141 as methyleneaminoacetonitrile, methylaminoacetonitrile and the caged compound hoxamethylenetetraamine, respectively. Isotopic analyses provided a high degree of confidence on the structural assignments of the ions at m/z 30 and 58 as methyleneimine and methyleneformamide; the ion at m/z 83, however, appeared to be a heterocyclic compound with daughter ion mass spectral elements similar to but not identical with that of 1‐methylimidazole and 3‐methylpyrazole.

Detection of 1,3,5-triazine derivatives in crop samples by thermolysis-atmospheric pressure ionization tandem mass spectrometry

Pulsed pyrolysis (Py) in combination with atmospheric pressure ionization (API) and tandem mass spectrometry was investigated as a method for detecting 1,3,5-triazine pesticide residues in agricultural matrices with minimal sample preparation. Analytes investigated were thermally stable and produced Py-API mass spectra that contained essentially only the protonated molecule. Collision-induced dissociation yielded daughter ions attributable to cleavage of the triazine ring. Limits of detection for analytes in crop samples ranged from 10−1 to 102 mg residue per kilogram of substrate, depending on the nature of both analyte and substrate.

Characterization of the reaction products of deoxyguanosine with the anticancer agent BFNU and BFNU-1,1,1′, 1′ -d4 in different buffers by high-performance liquid chromatography/atmospheric pressure ionization tandem mass spectrometry

The products of the reaction of the anticancer agent 1,3-bis(2-fluoroethyl)-1-nitrosourea (BFNU) and BFNU-1,1,1',1'-d4 with the DNA base deoxyguanosine were characterized by applying high-performance liquid chromatography (HPLC)/tandem mass spectrometry. The total effluent from the HPLC column was introduced into the atmospheric pressure ionization (API) source of a triple-quadrupole mass spectrometer via a heated nebulizer. The gasified mixture produced from the heated nebulizer was exposed to corona discharge ionization which led to generation of gas-phase chemical ionization type of ions. The LC/API mass spectrometry produced ions and the tandem mass spectra allowed unambiguous identification, and assignment of positions of the deuterium atoms, in the products of the reaction under a variety of experimental conditions. The identification and characterization of a variety of 7-(2'-haloethyl)guanine derivatives among the reaction products provide confirmation of a proposed mechanism for the action of BFNU on DNA bases.

Determination of the fragmentation mechanisms of organophosphorus ions by H2O and D2O atmospheric‐pressure ionization tandem mass spectrometry II—dialkyl alkylphosphonate ions

AbstractDiethyl methylphosphonate (DEMP), diisopropyl methylpbosphonate (DIMP), diethyl isopropylphosphonate (DEIP) and diethyl ethylphosphonate (DEEP) were characterized by H2O and D2O atmospheric pressure ionization tandem mass Spectrometry (API‐MS/MS). Collision‐induced dissociation (CID)/fragmentation pathways included alkyl ions by direct cleavage, alkyl radical and water loss processes and McLafferty and McLafferty‐type rearrangements by six‐ and five‐membered ring transition states, respectively. D2O API proved particularly useful in that certain decomposition pathways (i.e. water and methanol neutral losses) had a statistical distribution as to the loss of an acid deuteron and proton(s). This phenomenon was manifested by two pairs of ions in the D2O API daughter‐ion mass spectrum for each phosphonate compound (e.g. both m/z 79/80 and 65/66 for DEMP and DIMP). The observed ion intensity ratios for these pairs of ions served as guides in the determination of their predicted ion relative abundance ratios and CID decomposition pathways.Water neutral losses as opposed to ether and alcohol neutral losses were favored for most of the protonated organophosphonate molecular ion decomposition schemes.

Characterization of cyclotrimethylenetrinitramine (RDX) by N,H isotope analyses with pyrolysis–atmospheric pressure ionization tandem mass spectrometry

AbstractPyrolysis‐atmospheric pressure chemical ionization was used to study the thermal decomposition of the energetic material cyclotrimethylenetrinitramine (RDX) and characterization of the individual molecular ion products was accomplished by tandem mass spectrometry. The analysis was aided with pyrolysis mass spectra of the (15N)‐ and perdeuterated RDX isotopes, and molecular formulae were derived for the m/z 46, 60, 74, 75, 85 and 98 molecular ions in the RDX pyrolysis mass spectrum. Equivalent fragments between the daughter ion mass spectra of the unlabeled and labeled RDX were determined in order to define a structure for each pyrolysis feature. Daughter ion mass spectra of pure reference compounds confirmed the identity of five of the six molecular ions. Perdeuterated RDX analyses provided evidence that m/z 74 and 75 are N,N‐dimethylformamide and N‐nitrosodimethylamine, respectively; m/z 46, 60 and 85 were identified as the protonated forms of formamide, N‐methylformamide and dimethylaminoacetonitrile, respectively.