Coordination Ion Spray Mass Spectrometry Research Articles

Determination of triglycidyl isocyanurate from air samples by ultra-performance liquid chromatography coupled with coordination ion spray mass spectrometry.

Ultra-performance liquid chromatography (UPLC) coupled with coordination ion spray tandem mass spectrometry was used for the analysis of air samples containing triglycidyl isocyanurate. The method is not affected by any chromatographic interference and the filter extract is compatible with the UPLC system, as opposed to approaches using high-performance liquid chromatography coupled with ultraviolet detection and gas chromatography coupled with mass spectrometry. Accu-cap™ filters that had sampled triglycidyl isocyanurate were extracted using a mixture of acetonitrile/acetone (95/5) diluted with 3 volumes of water and were then analyzed. The mass spectrometry method uses sodium as the alkali adduct complexing with the triglycidyl isocyanurate in positive mode, and this complex is then analyzed using the survivor mode where the same ion is monitored in the first and third quadrupoles of a triple quadrupole mass spectrometer. The method has a limit of detection and limit of quantitation of 50 and 170 ng/filter, respectively. The dynamic range was between 480 and 24,000 ng/sample, which is equivalent to 2 µg/m(3) and 100 µg/m(3) based on a sampling volume of 240 L. The intra- and inter-day precisions were both <4% and the overall accuracy was 97 ± 3%. The method was tested with personal breathing zone random samples collected from workers using triglycidyl isocyanurate in their tasks, and all the random samples were easily quantified. A new method by UPLC coupled with coordination ion spray tandem mass spectrometry using sodium as the alkali adduct is now available for industrial hygienists who want to evaluate exposures of workers to triglycidyl isocyanurate in workplaces.

Liquid sulfur as a reagent: synthesis of polysulfanes with 20 or more sulfur atoms with characterization by UPLC-(Ag+)-coordination ion spray-MS

Diallyl disulfide reacts within minutes with liquid sulfur at 120°C giving a family of diallyl polysulfanes, All2S n (n=3–22), characterized by ultra-performance liquid chromatography-(Ag+)-coordination ion spray-mass spectrometry (UPLC-(Ag+)CIS-MS). Similarly, garlic oil (GO), bis-(2-methyl-2-propenyl), bis-(2-chloro-2-propenyl), bis-(3-methyl-2-butenyl), and bis-(2-cyclohexen-1-yl) disulfides all give families of polysulfanes with up to 22 sequential sulfur atoms. New members of families of silver chelators with up to 10 sulfur atoms were found in GO using UPLC-(Ag+)CIS-MS.

Novel product ions of 2-aminoanilide and benzimidazole Ag(I) complexes using electrospray ionization with multi-stage tandem mass spectrometry

The 2-aminoaniline scaffold is of significant value to the pharmaceutical industry and is embedded in a number of pharmacophores including 2-aminoanilides and benzimidazoles. A novel application of coordination ion spray mass spectrometry (CIS-MS) for interrogating the silver ion (Ag(+)) complexes of a homologous series of these compounds using multi-stage tandem mass spectrometry is described. Unlike the ubiquitous alkali metal ion complexes, Ag(+) complexes of 2-aminoanilides and benzimidazoles were found to yield [M - H](+) ions in significant abundance via gas-phase elimination of the metal hydride (AgH) resulting in unique product ion cascades. Sample introduction was by liquid chromatography with mass spectrometry analysis performed on a hybrid linear ion trap/orbitrap instrument capable of high-resolution measurements. Rigorous structural characterization by multi-stage tandem mass spectrometry using [M + H](+), [M - H](-) and [M - H](+) precursor ions derived from ESI and CIS experiments was performed for the homologous series of 2-aminoanilide and benzimidazole compounds. A full tabular comparison of structural information resulting from these product ion cascades was produced. Multi-stage tandem mass spectrometry of [M - H](+) ions resulting from Ag(+) complexes of 2-aminoanilides and benzimidazoles in CIS-MS experiments produced unique product ion cascades that exhibited complementary structural information to that obtained from tandem mass spectrometry of [M + H](+) and [M - H](-) ions by electrospray ionization (ESI). These observations may be broadly applicable to other compounds that are observed to form Ag(+) complexes and eliminate AgH.

One‐pot synthesis of a new antifungal polymerisable monomer and its characterisation by coordination‐ion spray mass spectrometry

We have investigated the synthesis of a new antifungal agent with a polymerisable moiety for the prevention of denture stomatisis. Nystatin (antifungal polyene) is modified in one step by reaction with isocyanatoethylmethacrylate to afford a new polymerisable antifungal agent in good yield (90%). In order to prove the monografting of the acrylate derivative and to localise the new group in the skeleton of the molecule, a rapid and efficient analytical method involving electrospray ionisation mass spectrometry (ESI-MS) was developed for the study. In view of the structures of such antifungal agents, their complexation with metal cations was investigated by Coordination-Ion Spray Mass Spectrometry (CIS-MS). This mass spectrometry study covers two aspects: improving the MS signal to overcome the low ionisation efficiency in ESI-MS and exploring the complexation behaviour of the induced structure to optimise the antifungal properties.

Dimer formation during the thermo-oxidation of stigmasterol

The monomeric oxidation products formed during the thermo-oxidation of phytosterols do not explain the loss of unoxidized phytosterols, leaving a gap in the knowledge on the products that are being formed during thermo-oxidation. Previous research showed that the gap can be explained by the formation of dimers and polymers. The aim of this research was to investigate the dimers that are formed during the thermo-oxidation of phytosterols, using stigmasterol as a model compound. Following the oxidation of stigmasterol at 180 °C, several dimeric fractions were obtained by solid phase extraction and high-performance size-exclusion chromatography. Individual dimers were separated by reversed-phase high-performance liquid chromatography, and their molecular masses were determined by combining atmospheric pressure chemical ionization-mass spectrometry and coordination-ion spray-mass spectrometry. This study resulted, for the first time, in the assignment of several individual stigmasterol dimers. The most dominant dimer was found to have a molecular mass of 822.7 Da and is suggested to represent a C–C linked dimer of stigmasterol, in accordance with literature. Several other stigmasterol dimers were found to be formed during thermo-oxidation, which are suggested to differ in monomeric subunit composition, linkage type, and stereochemistry.

Allium chemistry: Use of new instrumental techniques to “see” reactive organosulfur species formed upon crushing garlic and onion

Three different instrumental methods have been used to examine the organosulfur chemistry of intact and cut garlic and onions: X-ray fluorescence spectroscopic imaging (XFS), direct analysis in real time (DART) mass spec-trometry, and ultra-performance liquid chromatography-(Ag+)-coordination ion spray mass spectrometry (UPLC–(Ag+)CIS–MS). The first technique has been used to map the location of different chemical forms of sulfur in intact and damaged onion cells, the second technique, to identify the reactive, volatile sulfur compounds formed on cutting the plants, and the third technique, to identify members of families of polysulfides found in the distilled oil of garlic.

Enhancing the detection sensitivity of trace analysis of pharmaceutical genotoxic impurities by chemical derivatization and coordination ion spray-mass spectrometry

Many pharmaceutical genotoxic impurities are neutral molecules. Trace level analysis of these neutral analytes is hampered by their poor ionization efficiency in mass spectrometry (MS). Two analytical approaches including chemical derivatization and coordination ion spray-MS were developed to enhance neutral analyte detection sensitivity. The chemical derivatization approach converts analytes into highly ionizable or permanently charged derivatives, which become readily detectable by MS. The coordination ion spray-MS method, on the other hand, improves ionization by forming neutral-ion adducts with metal ions such as Na +, K +, or NH 4 + which are introduced into the electrospray ionization source. Both approaches have been proven to be able to enhance the detection sensitivity of neutral pharmaceuticals dramatically. This article demonstrates the successful applications of the two approaches in the analysis of four pharmaceutical genotoxic impurities identified in a single drug development program, of which two are non-volatile alkyl chlorides and the other two are epoxides.

New Insights Regarding the Autoxidation of Polyunsaturated Fatty Acids

Free radical-initiated autoxidation of polyunsaturated fatty acids (PUFAs) has been implicated in numerous human diseases, including atherosclerosis and cancer. This review covers the free radical mechanisms of lipid oxidation and recent developments of analytical techniques to analyze the lipid oxidation products. Autoxidation of PUFAs generates hydroperoxides as primary oxidation products, and further oxidation leads to cyclic peroxides as secondary oxidation products. Characterization of these oxidation products is accomplished by several mass spectrometric techniques. Ag+ coordination ion spray mass spectrometry has proven to be a powerful tool to analyze the intact lipid peroxides. Monocyclic peroxides, bicyclic endoperoxides, serial cyclic peroxides, and a novel class of endoperoxides (dioxolane-isoprostane peroxides) have been identified from the oxidation of arachidonate. Electron capture atmospheric pressure chemical ionization mass spectrometry has been applied to study lipid oxidation products after derivatization. All eight possible diastereomeric isoprostanes are observed from the oxidation of a single hydroperoxide precursor. 5- and 15-series isoprostanes are more abundant than the 8- and 12-series because the precursors that lead to 8- and 12-series compounds can undergo further oxidation and form dioxolane-isoprostane peroxides. Furthermore, formation of isoprostanes from 15-hydroperoxyeicosatetraenoate occurs from beta-fragmentation of the corresponding peroxyl radical to generate a pentadienyl radical rather than a "dioxetane" intermediate, as previously suggested.

High‐performance liquid chromatography–coordination ion spray–mass spectrometry (HPLC‐CIS/MS): a new tool for the analysis of non‐polar compound classes in plant extracts using the example of Piper methysticum forst

An efficient method to characterise complex plant extracts is described using the example of Piper methysticum Forst. (kava; Piperaceae). The method is based on the on-line coupling of high-performance liquid chromatography to a new detection technique: coordination ion spray-mass spectrometry (CIS/MS). CIS/MS is a universal, novel ionisation technique improving selectivity as well as sensitivity. Charged complexes were formed through addition of central complexing ions such as sodium, silver and cobalt. The advantages of CIS/MS detection compared with the electrospray ionisation detection are discussed. The experimental set-up and the application of this simple and robust technique is described to show the its various fields of application in the analysis of plant extracts.

Liquid chromatography coordination ion-spray mass spectrometry (LC-CIS-MS) of docosahexaenoate ester hydroperoxides.

Coordination ion-spray mass spectrometry (CIS–MS) is a useful tool in the detection and identification of complex mixtures of cholesterol ester and phospholipid hydroperoxides. The methyl ester, cholesterol ester, and phospholipid hydroperoxides of docosahexaenoic acid were analyzed by LC–CIS–MS and their elution orders were identified. Their corresponding alcohols were also identified. The methyl hydroperoxydocosahexaenoate (HPDHE) elution order is 14, 17, 16, 13, 20, 11, 10, 4, 7, 8 while the methyl hydroxydocosahexaenoate (HDHE) elution order is 14 ≥ 17, 16, 13, 11, 10, 20, 7, 8, 4. The cholesteryl HPDHE elution order is 14, 17, 16, 13, 20, 11 ≥ 10, 4, 7, 8 and the cholesteryl HDHE elution order is 17, 14, 16, 13, 11, 20, 10, 7, 8, 4. The elution order of the 1-palmitoyl-2-docosahexaenoyl-sn-glycero-3-phosphatidylcholine (PDPC) hydroperoxides and alcohols is 20, 16, 17, 13, 14, 10, 11, 7, 8, 4.

Liquid chromatography coordination ion-spray mass spectrometry (LC-CIS-MS) of docosahexaenoate ester hydroperoxides.

Coordination ion-spray mass spectrometry (CIS-MS) is a useful tool in the detection and identification of complex mixtures of cholesterol ester and phospholipid hydroperoxides. The methyl ester, cholesterol ester, and phospholipid hydroperoxides of docosahexaenoic acid were analyzed by LC-CIS-MS and their elution orders were identified. Their corresponding alcohols were also identified. The methyl hydroperoxydocosahexaenoate (HPDHE) elution order is 14, 17, 16, 13, 20, 11, 10, 4, 7, 8 while the methyl hydroxydocosahexaenoate (HDHE) elution order is 14 > or = 17, 16, 13, 11, 10, 20, 7, 8, 4. The cholesteryl HPDHE elution order is 14, 17, 16, 13, 20, 11 > or = 10, 4, 7, 8 and the cholesteryl HDHE elution order is 17, 14, 16, 13, 11, 20, 10, 7, 8, 4. The elution order of the 1-palmitoyl-2-docosahexaenoyl-sn-glycero-3-phosphatidylcholine (PDPC) hydroperoxides and alcohols is 20, 16, 17, 13, 14, 10, 11, 7, 8, 4.

Analysis of unsaturated compounds by Ag + coordination ionspray mass spectrometry : studies of the formation of the Ag +/lipid complex

Coordination ionspray mass spectrometry (CIS-MS) is a useful tool in the detection and identification of cholesterol ester and phospholipid hydroperoxides and diacyl peroxides. Extensive studies of a series of cholesterol esters using CIS-MS revealed the following: (1) Cholesterol esters with equal number of double bonds as the internal standard showed a linear relative response in the mass spectrometer while compounds with non-equal numbers of double bonds gave a nonlinear relative response. (2) Complex adducts containing cholesterol ester, silver ion, AgF, AgBF 4, and 2-propanoxide form when silver is in molar excess of cholesterol esters, reducing the [M + Ag] + signal. (3) In a mixture of cholesterol esters where silver is limiting, Ch22:6 and Ch20:4 bind to silver at the expense of Ch18:2 and have a higher signal in the mass spectrometer. (4) In a mixture of cholesterol esters where silver concentration is twofold greater than total cholesterol ester concentration, Ch22:6 and Ch20:4 form large complex adducts more frequently than Ch18:2 and have a lower signal in the mass spectrometer.

On-line coupling of packed capillary electrochromatography with coordination ion spray-mass spectrometry for the separation of enantiomers.

Pressure-supported packed capillary electrochromatography (CEC) and packed capillary high-performance liquid chromatography (pHPLC) have been coupled on-line to electrospray ionization-mass spectrometry (ESI-MS) and coordination ion spray-mass spectrometry (CIS-MS). Separation of enantiomers of barbiturates and chlorinated alkyl phenoxypropanoates were performed on a permethylated beta-cyclodextrin stationary phase by pressure-supported CEC. For on-line detection with ESI- and CIS-MS, a modified sheath-liquid interface was used. CIS-MS is a universal, novel ionization technique which improves the selectivity as well as the sensitivity. Charged complexes were formed through the addition of central complexing ions such as silver(I), cobalt(II), copper(II), and lithium(I) to the sheath flow. Advantages of CIS-MS detection compared to the ESI-MS mode are discussed. In the CIS-MS mode, increased sensitivity and high selectivity was attained through different possibilities of complexation. The superiority of pressure-supported CEC compared to pHPLC in the hyphenation with CIS-MS is demonstrated.

Separation and identification of phospholipid peroxidation products.

The molecular species in mixtures of phospholipid hydroperoxides are difficult to separate and identify by typical chromatographic and mass spectrometric techniques. As reported by Havrilla and coworkers, silver ion coordination ion-spray mass spectrometry (CIS-MS) has proven to be a powerful technique for the identification of mixtures of hydroperoxides. This ionization technique, which involves the formation of Ag+ adducts of the hydroperoxides, provides valuable, unambiguous structural information about the hydroperoxides. Herein, we report a method for the analysis and identification of phospholipid hydroperoxides using CIS-MS. We also report an improved method for the separation of phospholipid hydroperoxides by reversed-phase high-performance liquid chromatography (RP-HPLC), which, for the first time, separates some of the hydroperoxide isomers. CIS-MS can be coupled with this RP-HPLC method by the addition of AgBF4 to the mobile phase or to the HPLC effluent postcolumn, thus allowing powerful HPLC-MS techniques to be used to identify complex mixtures of phospholipid hydroperoxides.

Coupling of capillary electrochromatography to coordination ion spray mass spectrometry, a novel detection method.

Miniaturized separation techniques such as capillary electrochromatography (CEC), pressurized capillary electrochromatography (pCEC) and capillary high performance liquid chromatography (CHPLC) have been coupled to a new detection technique: coordination ion spray mass spectrometry (CIS-MS). Electrospray ionization (ESI) has found widespread applications in mass spectrometry (MS) for the analysis of polar compounds such as peptides or nucleotides. However, for weakly polar or nonpolar substances, ESI-MS yields poor sensitivity since, in the absence of basic or acidic groups, protonation or deprotonation is not possible. CIS is a universal ionization technique capable of detecting these compounds. Through the addition of a central complexing ion, charged coordination compounds are formed, enabling the detection with good sensitivity. Using the coaxial sheath flow interface commonly employed in CE-MS coupling, we were able to separate and detect various important natural compounds such as unsaturated fatty acid methyl esters, vitamins D2 and D3, and four different estrogens. A central ion solution of 100 microg/mL AgNO3 in water was used as sheath flow liquid, resulting in the formation of positively charged coordination compounds.