Intensity Exaggeration of Endohedral Metallofullerenes in Laser Desorption-Ionization Time-of-Flight Mass Spectrometry

Massspectrometryhasplayedacriticalroleinthefullereneresearchesl-8.ItwillalsobeheIpfulinthestudyofendohedralmetallofullerenes6.Eventhoughtherehavebeenplentyofreportsonmet.ll.fullerenes'-",detailedstudiesabouttheirgas-phasebehaviorareverypoor.Inthisletter,wereportanunusualintensityexaggerationphenomenonofendohedralmetallofullerenesinLD-TOFmassspectrometry,whichisconsideredduetotheirpeculiarionizationenergiesandelectronaffinities.SootcontainingmetallofullereneswassynthesizedbyK-Hcarbonarcevap…     

Unusual Fragmentation of Peptide and Protein in Matrix-assisted Laser Desorption/lonization Mass Spectrometry

Unusual amine - bond fragmentation on the peptide/protein backbone has been reported using matrix - assisted laser desorption/ionization time - of- flight mass spectrometry (MALDI - TOFMS)The amine - bond cleavage occurred without metastable decay, while the peptide - bond cleavage occurred with metastable decay of peptide ions in a drift region of TOF mass analyzer. It was presumed that the amine - bond cleavage occurred as a non - ergodic process independent of the ionization under MALDI conditions.     

Determination of Mildronate in Human Plasma and Urine by UPLC�CPositive Ion Electrospray Tandem Mass Spectrometry

A simple, rapid, and selective method to determine the concentration of mildronate in human plasma and urine using ultra performance liquid chromatography?Ctandem mass spectrometry (UPLC-MS-MS) was developed and validated. The detection was performed on a triple-quadrupole tandem mass spectrometer by multiple reaction monitoring mode via electrospray ionization at m/z 147.2?C58.0 for mildronate and m/z 147.2?C87.8 for the internal standard, carbachol. The UPLC separation was carried out with a UPLC BEH HILIC column. The mobile phase consisted of 0.08% formic acid in 30 mM ammonium acetate solution and acetonitrile (23:77, v/v). Plasma samples were extracted from plasma by protein precipitation and urine samples were diluted with the mobile phase. The analysis time was 3.5 min for each sample. Linear calibration curves ranged from 0.10 to 100.00 ??g mL^?1 in human plasma and 0.50 to 600.00 ??g mL^?1 in urine. The method had been successfully applied to a pharmacokinetic study in healthy volunteers. After single intravenously administration of 250, 500, and 750 mg mildronate, the elimination half-life (t _1/2) were (2.74 ± 0.67), (4.86 ± 0.82) and (5.16 ± 0.77) h, respectively. The t _1/2 for the 250 mg dose did vary significantly with other dosages (P < 0.05), mildronate may have non-linear pharmacokinetics in humans.     

Stereochemical Effects in Mass Spectrometry ( Ⅶ )——Negative Ion Fast Atom Bombardment Mass Spectro-metry of Saccharides with Areneboronic Acids as Reagents

1-Naphthylboronic acid and 2, 4-dimethylphenylboronic acid can react stereospecif-ically with hydroxy groups of saccharides on the probe tip of a fast atom bombardment mass spectrometer to form characteristic negatively-charged boronate ions. On the basis of the relative abundances of these characteristic ions, the epimers of mono- and di-saccharides may be distinguished. This approach was proved to be a simple and effective means for identifying sugars. The collisional activation moss spectra of these characteristic ions are also discussed.     

Topography and Field Effects in Secondary Ion Mass Spectrometry – Part I: Conducting Samples

Quantitative chemical characterization of surfaces with topography by secondary ion mass spectrometry (SIMS) remains a significant challenge due to the lack of systematic and validated measurement methods. In this study, we combine an experimental approach using a simple model system with computer simulation using SIMION, to understand and quantify the key factors that give rise to unwanted topographic artefacts in SIMS images of conducting samples with microscale topography. Experimental data are acquired for gold wires (diameters 33 to 125 μm) mounted onto silicon wafers. Significant loss of ion intensities and shadowing arise from the distortion of the extraction field, and the chemical analysis over the whole of the sample surface is difficult. For large primary ion incidence angles of ≥55° to the surface normal, a fraction of the primary ions are scattered from the target and impact the substrate, emitting secondary ions that may be mistaken as originating from the wire. For conducting samples, topographic field effects may be reduced by the use of a smaller extraction voltage and an extraction delay. The effects of an extraction delay on ion intensities, mass resolution and time-of-flight are studied, and its application is demonstrated on an anisotropically etched silicon sample. The use of a simple sample holder with a V-shaped groove to reduce topographic field effects for wires is also presented. Using these results, we provide clear guidance to analysts for the diagnosis and identification of topography effects in SIMS, and present key recommendations to minimize them in practical analysis.     

Gas Chromatography–Mass Spectrometry Determination of Morphine and Codeine in Blood as Their Propionic Esters

A gas-chromatographic separation procedure with mass-spectrometric detection was developed for the detection of opiates in whole blood and the quantitative determination of morphine and codeine as their propionic esters. The detection limit for morphine and codeine in blood was 0.02 g/mL. The analytical range was 0.05–2.0 g/mL. The maximum intraseries relative errors were 15.6 and 11.2% for concentrations of 0.05 and 1.0 g/mL, respectively. The interseries relative errors were no higher than 8 and 3% for concentrations of 0.05 and 1.0 g/mL, respectively. The procedure is intended for forensic chemical analysis in cases of opiate poisoning.     

Separation and Quantification of Key Starting Materials of Irbesartan Using Liquid Chromatography–Mass Spectrometry as a Separation and Identification Tool

Abstract

A liquid chromatography–mass spectrometry (LC-MS) method was developed and validated for determining the levels of 4-methyl-2-cyano biphenyl and 4-bromomethyl-2-cyano biphenyl, which are key starting materials of an antihypertensive drug substance, irbesartan. An active pharmaceutical ingredient of irbesartan was synthesized by using these two starting materials for its therapeutic use. We have explicated the LC-MS method to separate and quantify these two compounds in irbesartan at nanogram levels. The method was capable of separating irbesartan and its starting materials, which were monitored for their absence in the finished product of irbesartan. The separation was carried out at 40°C on a 150- × 4.6-mm cyano column by using the mobile phase containing 60 volumes of water adjusted to pH 3.2 with formic acid and 40 volumes of acetonitrile. The detection wavelength was 220 nm. The MS involved an electrospray ionization (ESI) probe and ion-trap analyzer and was validated with respect to its specificity, accuracy, and precision.     

Liquid Chromatography–Single-Quadrupole Mass Spectrometry as a Responsive Tool for Determination of Biogenic Amines in Ready-to-Eat Baby Foods

Baby food has never been the object of biogenic amine profiling. The aim of this study was to develop a highly sensitive method for analysis of biogenic amines in ready-to-eat baby foods. The principle of the developed method involves high-performance liquid chromatography coupled to single-quadrupole mass spectrometry (HPLC–APCI–MS) of dansyl derivatives, presented also in comparison with common diode array and fluorescence detection systems. The confirmation of correct identification of derivatives was performed by in-source fragmentation of the product ion at 170 m/z, performed only in one MS analyzer. The method was used to identify the amine profile and quantify the putrescine, cadaverine, histamine, tyramine, spermidine, and spermine content in 68 ready-to-eat baby foods. The limits of detection and quantification were in the range of 0.07–1.67 and 0.2–5.0 ng mL^??1. The method enabled quantification of amines at ng/g level in almost all analyzed samples, without any preconcentration step. Amine recoveries of 86.0–105.2% were obtained with RSD?≤?9.7%. The developed method could be used for quantification of the most frequently occurring BAs in foods including vegetables, fish, meat, or fruit at previously undetectable concentration levels, making the method multimatrix applicable and highly-sensitive.     

Rapid Evaluation of the Bioremediation of Fuel Oil in Soil by Gas Chromatography–Laser Ionization Time-of-Flight Mass Spectrometry

Gas chromatography–laser ionization time-of-flight mass spectrometry (GC-LI-TOFMS) was applied to the analysis of fuel oil in soil and soil treated by bioremediation. To demonstrate rapid and selective measurement, only filtered samples after extraction of fuel oil from soil were prepared. The required time for preparing three sample solutions from an oil-contaminated soil sample was only ca. 30?min. The degree of the decrease in the fuel oil in a soil sample by vaporization was confirmed by GC-LI-TOFMS, and after 7 days, the five peak areas arising from the constituents in fuel oil were decreased to between 39 and 79% of their original values. Next, the effect of bioremediation was confirmed by the addition of microbes (Rhodococcus sp. and Acinetobacter sp.). As a result, after 7 days, the five peak areas were decreased to between 61 and 81% of the values of the first decreases, after allowing for the effect of vaporization. This method showed sufficient selectivity, robustness, and rapidity for the measurement of oil-contaminated soil treated by bioremediation, which is essential for the evaluation of real environmental remediation.     

Signatures of Mechanically Interlocked Topology of Lasso Peptides by Ion Mobility–Mass Spectrometry: Lessons from a Collection of Representatives

Lasso peptides are characterized by a mechanically interlocked structure, where the C-terminal tail of the peptide is threaded and trapped within an N-terminal macrolactam ring. Their compact and stable structures have a significant impact on their biological and physical properties and make them highly interesting for drug development. Ion mobility - mass spectrometry (IM-MS) has shown to be effective to discriminate the lasso topology from their corresponding branched-cyclic topoisomers in which the C-terminal tail is unthreaded. In fact, previous comparison of the IM-MS data of the two topologies has yielded three trends that allow differentiation of the lasso fold from the branched-cyclic structure: (1) the low abundance of highly charged ions, (2) the low change in collision cross sections (CCS) with increasing charge state and (3) a narrow ion mobility peak width. In this study, a three-dimensional plot was generated using three indicators based on these three trends: (1) mean charge divided by mass (ζ), (2) relative range of CCS covered by all protonated molecules (ΔΩ/Ω) and (3) mean ion mobility peak width (δΩ). The data were first collected on a set of twenty one lasso peptides and eight branched-cyclic peptides. The indicators were obtained also for eight variants of the well-known lasso peptide MccJ25 obtained by site-directed mutagenesis and further extended to five linear peptides, two macrocyclic peptides and one disulfide constrained peptide. In all cases, a clear clustering was observed between constrained and unconstrained structures, thus providing a new strategy to discriminate mechanically interlocked topologies.

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Cyanide–Arene Meisenheimer Complex Generated in Electrospray Ionization Mass Spectrometry Using Acetonitrile as a Solvent

The C – C bond formation activated under negative electrospray ionization of an acetonitrile solution of 1,3,5-trinitrobenzene is reported. The solvent function is to provide a source of cyanide ion, a highly problematic reagent, which is found to attack the electron-deficient aromatic ring to form a covalently bound anionic complex (Meisenheimer complex). The structure of the complex is elucidated by means of collision induced dissociation mass spectrometry and IR multiple photon dissociation spectroscopy in the ‘fingerprint’ region.

Analytical Study of a Resinous Material Used as Sealing in Ancient Pottery Found in an Archaeological Site by Thermally Assisted Hydrolysis Methylation–Gas Chromatography–Mass Spectrometry,Vibrational Spectroscopy and Light Microscopy

Abstract

A resin sample was found in the archaeological site of Lixus (Morocco), belonging to the second century BC. The resinous material was found inside an amphora containing iron remains used in the plug as sealing material to hermetically close the pottery. The resinous sample was studied by several analytical techniques, as thermally assisted hydrolysis and methylation–gas chromatography–mass spectrometry (THM–GC–MS), Fourier transformed infrared spectroscopy (FTIR), and light microscopy. The material was identified as a Pinaceae resin. Therefore, a modern pine resin was also analyzed to consider the influence of aging in the archaeological sample. The ancient material was found not too oxidized, owing to the conservation conditions inside the amphora, protected from air and moisture.     

Native Top-Down Mass Spectrometry and Ion Mobility MS for Characterizing the Cobalt and Manganese Metal Binding of α-Synuclein Protein

Structural characterization of intrinsically disordered proteins (IDPs) has been a major challenge in the field of protein science due to limited capabilities to obtain full-length high-resolution structures. Native ESI-MS with top-down MS was utilized to obtain structural features of protein-ligand binding for the Parkinson’s disease-related protein, α-synuclein (αSyn), which is natively unstructured. Binding of heavy metals has been implicated in the accelerated formation of αSyn aggregation. Using high-resolution Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometry, native top-down MS with various fragmentation methods, including electron capture dissociation (ECD), collisional activated dissociation (CAD), and multistage tandem MS (MS³), deduced the binding sites of cobalt and manganese to the C-terminal region of the protein. Ion mobility MS (IM-MS) revealed a collapse toward compacted states of αSyn upon metal binding. The combination of native top-down MS and IM-MS provides structural information of protein-ligand interactions for intrinsically disordered proteins.

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Ion/Neutral,Ion/Electron,Ion/Photon,and Ion/Ion Interactions in Tandem Mass Spectrometry: Do We Need Them All? Are They Enough?

A range of strategies and tools have been developed to facilitate the determination of primary structures of analyte molecules of interest via tandem mass spectrometry (MS/MS). The two main factors that determine the primary structural information present in an MS/MS spectrum are the type of ion generated from the analyte molecule and the dissociation method. The ion type subjected to dissociation is determined by the ionization method/conditions and ion transformation processes that might take place after initial gas-phase ion formation. Furthermore, the range of analyte-related ion types can be expanded via derivatization reactions prior to mass spectrometry. Dissociation methods include those that simply alter the population of internal states of the mass-selected ion (i.e., activation methods like collision-induced dissociation) as well as processes that rely on the transformation of the ion type prior to dissociation (e.g., electron capture dissociation). A variety of ion interactions have been studied for the purpose of ion dissociation and ion transformation, including ion/neutral, ion/photon, ion/electron, and ion/ion interactions. A wide range of phenomena have been observed, many of which have been explored/developed as means for structural analysis. The techniques arising from these phenomena are discussed within the context of the elements of structural determination in tandem mass spectrometry: ion-type definition and dissociation. Unique aspects of the various ion interactions are emphasized along with any barriers to widespread implementation.     

Determination of Toluene and Ethanol in Urine by Headspace and Cryotrapping Gas Chromatography–Mass Spectrometry

Toluene is the major volatile organic compound found in glue and is often used as a hallucinogenic for abusers. Use with alcohol increases the risk of adverse effects from toluene exposure. In this study, a headspace and cryotrapping gas chromatography–mass spectrometry method was developed and validated for the determination of toluene and ethanol in urine. Experimental and instrumental variables were investigated to optimize the method for sensitivity. Excess sodium sulfate was used as the salting-out reagent before the headspace protocol. Linear least squares regression with a 1/x weighting factor was used to construct calibration curves from 0.002 to 0.4?µg?mL^?1 for toluene and 10 to 2000?µg?mL^?1 for ethanol. The correlation coefficients exceeded 0.9993. The limits of detection were 0.0005?µg?mL^?1 for toluene and 0.21?µg?mL^?1 for ethanol. Intraday and interday precisions were within 5.4 and 11.5%, while intraday and interday accuracies were between ?11.3 to ?4.0% and ?11.0 to 1.2%, respectively. The method validation results for selectivity and stability were satisfactory. The validation results were used to estimate the expanded uncertainty and the contribution of individual steps in the method for the quantification of toluene and ethanol. The relative expanded uncertainties were 14.1% for toluene and 4.6% for ethanol.     

Trace Determination of Manganese in Urine by Graphite Furnace Atomic Absorption Spectrometry and Inductively Coupled Plasma–Mass Spectrometry

This paper describes a simple and sensitive method for the determination of manganese in human urine by graphite furnace atomic absorption spectroscopy (GFAAS), which includes sample preparation by microwave digestion. Matrix modifier combinations, the digestion power, pyrolysis, and atomization temperatures were optimized. A mixture of 5.0 µg Pd(NO₃)₂ and 3.2 µg Mg(NO₃)₂ modifier presented the best performance. The optimal temperatures for pyrolysis and atomization were 1500°C and 1950°C, respectively. The GFAAS method was compared to inductively coupled plasma–mass spectrometry (ICP–MS) for the determination of manganese in urine. Analytical figures of merit for GFAAS and ICP–MS were: accuracy (3.46%, 2.19%), precision (3.61%, 5.84%), LOD (0.109 µg · L^?1, 0.015 µg · L^?1), LOQ (0.327 µg · L^?1, 0.045 µg · L^?1), and recovery (80–100%, 74–89%). Both methods were employed for the determination of Mn in urine and the results were compared statistically.     

Characterization of the Ion Beam Focusing in a Mass Spectrometer Using an IonCCD™ Detector

A position sensitive pixel-based detector array, referred to as the IonCCD, has been employed to characterize the ion optics and ion beam focusing in a custom built mass spectrometer designed for soft and reactive landing of mass-selected ions onto surfaces. The IonCCD was placed at several stages along the path of the ion beam to determine the focusing capabilities of the various ion optics, which include an electrodynamic ion funnel, two radiofrequency (rf)-only collision quadrupoles, a mass resolving quadrupole, a quadrupole bender, and two einzel lens assemblies. The focusing capabilities of the rf-only collision quadrupoles and einzel lenses are demonstrated by large decreases in the diameter of the ion beam. In contrast, the mass resolving quadrupole is shown to significantly defocus the mass-selected ion beam resulting in an expansion of the measured ion beam diameter. Combined with SIMION simulations, we demonstrate that the IonCCD can identify minor errors in the alignment of charged-particle optics that result in erratic trajectories and significant deflections of the ion beam. This information may be used to facilitate the design, assembly, and maintenance of custom-built mass spectrometry instrumentation.     

Laser ablation synthesis of new phosphorus nitride clusters from α-P3N5 via Laser Desorption Ionization and Matrix Assisted Laser Desorption Ionization Time-Of-Flight Mass Spectrometry

Phosphorus nitride clusters generated during Laser Desorption Ionization (LDI) and Matrix-Assisted Laser Desorption Ionization (MALDI) of solid P(3) N(5) were analyzed via Time-of-Flight Mass Spectrometry (TOF MS). The LDI TOF mass spectra show the formation of series of clusters: P(m)N(n)(+) {(m=1; n=8-11), (m=4; n=3-4), (m=5; n=1-5), (m=6; n=1-3, 5-8), (m=2-7; n=1), (m=5-10; n=2), (m=4-6; n=3), (m=4,5; n=4), (m=5,6; n=5)}, and P(m)N(n)(-) (m=4,5; n=1). Using 3-hydroxypicolinic acid (HPA) as a matrix the P(m)N(n)(+) species (m=1-4, 6, 8) with a high nitrogen content (n=4, 5, 8, 10-12, 20) were identified. The formation of a N(6)(-) cluster was also detected using a C(60) matrix. Under various conditions singly charged P(m)(+) (m=2-7, 9, 13), P(m)(-) (m=3-11, 13, 15, 17), N(n)(+) (n=5, 9, 10, 12, 13), and N(n)(-) (n=6, 10-15) clusters were identified in the mass spectra. Such high nitrogen content clusters (up to N(15)(-)) generated by laser desorption from a solid material are described for the first time. The stoichiometry of the P(m)N(n) clusters was determined via isotopic envelope analysis and computer modelling. The composition of the clusters with respect to the crystalline structure of α-P(3)N(5) is discussed.     

Determination of Ketotifen Fumarate in Raw Material and Pharmaceutical Products Using Ion‐pair Formation

Abstract

A simple and sensitive extractive spectrophotometric method has been described for the determination of Ketotifen. The developed method is based on the formation of a colored ion‐pair complex (1∶1 drug/dye) of Ketotifen and bromocresol green in buffer pH 3 and extraction in chloroform. The extracted complex shows absorbance maxima at 423 nm. Beer's law is obeyed in the concentration range of 5.15–61.91 µg/ml. The proposed method has been applied successfully for the determination of drug in commercial tablets and syrup dosage form. No significant interference was observed from the excipients commonly used as pharmaceutical aids with the assay procedure.