Collision Voltage Research Articles

Optimization of dissociation efficiency in small linear ion trap mass spectrometer

Abstract Small linear ion trap mass spectrometers are often combined with direct ionization mass spectrometry (DIMS) techniques for detection and analysis. However, DIMS is susceptible to the working environment and matrix effects, resulting in reduced sensitivity, which places high demands on the performance of tandem mass spectrometry of small linear ion trap mass spectrometers. Therefore, the effects of vacuum pressure, collision q-value, collision voltage, and collision time on the dissociation efficiency of the ion trap are experimentally explored in this paper to enhance the performance of tandem mass spectrometry for small linear ion trap mass spectrometers. The findings indicate that as the vacuum pressure increases, dissociation efficiency first increases rapidly and then remains stable, and the peak dissociation efficiency of 56% is attained at a vacuum pressure of 0.31 mTorr. Increasing the collision q value, dissociation efficiency first increased slowly, then increased rapidly, and finally remained almost unchanged. When the collision q value was increased from 0.26 to 0.35, dissociation efficiency increased from 9% to 56%. Meanwhile, the maximum collision voltage corresponding to the optimal dissociation efficiency gradually decreases as the collision q value increases. With the increase in collision time, dissociation efficiency increases rapidly and then remains stable. Therefore, studying the factors affecting dissociation efficiency points the way to enhancing the efficacy of tandem mass spectrometry with small linear ion trap mass spectrometers.

Determination of nobiletin and tangeretin in rat plasma by ultra-performance liquid chromatography-tandem mass spectrometry and study of their pharmacokinetics

AbstractAn ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed for the determination of nobiletin and tangeretin in rat plasma, and the plasma was processed by a simple liquid-liquid extraction method with ethyl acetate. The chromatographic column was UPLC HSS T3 (50 × 2.1 mm, 1.7 μm), the mobile phase was acetonitrile-water (containing 0.1% formic acid). Multiple reaction monitoring mode (MRM) was used for quantitative analysis, nobiletin m/z 403.29 → 373.14 (cone voltage 22v, collision voltage 28v), tangeretin m/z 373.28 → 343.17 (cone voltage 20v, collision voltage 28V), tangeretin m/z 373.28 → 343.17 (cone voltage 20V, collision voltage 28V) and internal standard vitexin m/z 433.14 → 313.03 (cone voltage 32v, collision voltage 26v). The pharmacokinetics of nobiletin and tangeretin were evaluated in rats. The established UPLC-MS/MS method in the range of 2–2,000 ng mL−1 was successfully applied to the pharmacokinetics, and the calculated bioavailability of nobiletin and tangeretin was 63.9 and 46.1%, respectively.

Petroleomics by design of experiments in ESI(±)FT-ICR MS analysis

The Fourier Transform Ion Cyclotron Resonance mass spectrometer (FT-ICR MS) is an efficient and widely used analytical instrument for characterizing complex organic mixtures at the molecular level. The Electrospray ionization (ESI) source is commonly used for identifying heteroatomic compounds (N, O, S) in crude oil. The high complexity of the sample provides a wealth of information, and therefore, processing and visualization programs are used to facilitate data interpretation. Several experimental configurations of parameters exist for the acquisition of ESI(+)FT-ICR MS and ESI(-)FT-ICR MS of crude oils. In this context, the design of experiments can help obtain optimal test conditions. The objective of this work was to identify the most significant experimental parameters among the 11 available (concentration, skimmer, time of flight (TOF), flow rate, ion accumulation time (IAT), accumulated scans (scans), dry temperature, capillary, dry gas, nebulizer, and collision voltage (CV)) for the acquisition of ESI(±)FT-ICR MS in Petroleomics using design of experiments by Plackett Burman and full design. Global desirability was used as a response parameter obtained from MS data (resolution, signal-to-noise ratio, signal-to-charge ratio signal with highest absolute intensity, total signals, low mass error, and high mass error). Additionally, responses from the mass spectra processing program were also used (the number of molecular formulas, molecular formulas of the majority class, average error, assignment percentage, amount of DBE in the plot of DBE versus carbon number (CN), and the relationship between the number of zero intensities and the number of DBE values in the plot of DBE versus CN). The study found that concentration and flow rate were the most significant experimental parameters for ESI(+), while for ESI(-), TOF and CV were the most significant experimental parameters. Lower concentration (0.1–0.5 mg/mL) and higher flowrate (5–6 µL/min) improved the desirability by ESI(+), higher values of CV (50 V) improved the desirability by ESI(-) for crude oil analysis.

Determination of 41 veterinary drug residues in livestock and poultry meat using a composite purification system coupled with direct analysis in real time-tandem mass spectrometry

In a market environment where food safety problems still occur despite repeated prohibitions, food safety problems caused by veterinary drug residues and biological safety problems caused by the transfer of drug resistance have attracted much attention. Herein, a method based on a compound purification system coupled with direct analysis in real time-tandem mass spectrometry (DART-MS/MS) was established to determine 41 different types of veterinary drug residues in livestock and poultry products. First, a single-standard solution sampling method was used to optimize the selection of the best quasi-molecular ion, two daughter ions, and their cone-hole and collision voltages; qualitative and quantitative ion pairs are composed of a quasi-molecular ion and its corresponding daughter ion. The abundance ratios of the drug compounds in standard solutions of the solvent and matrix mixtures were then calculated according to the requirements of the European Union 2002/657 specification. DART-MS/MS was subsequently developed for the accurate characterization and quantitative analysis of the veterinary drugs. Finally, a composite purification pretreatment system was formed by combining the primary secondary amine (PSA) and octadecyl bonded silica gel (C18) of a QuEChERS technology with multiwalled carbon nanotubes (MWCNTs) to achieve the one-step purification of the drug compounds. The influence of the key parameters of the DART ion source on the determination of the drugs was investigated using the peak areas of the quantitative ions as the criterion. The optimum conditions were as follows: ion source temperature of 350 ℃, 12-Dip-it Samplers module, sample injection speed of 0.6 mm/s, and external vacuum pump pressure of -75 kPa. According to the differences in the dissociation constant (pKa) ranges of the 41 types of veterinary drug compounds and the characteristics of the sample matrixes, the extraction solvent, matrix-dispersing solvent, and purification method were optimized based on the recovery. The extraction solvent was 1.0% acetonitrile formate solution, and the pretreatment column included MWCNTs containing 50 mg of PSA and 50 mg of C18. The three chloramphenicol drugs showed a linear relationship in the ranges of 0.5-20 μg/L with correlation coefficients of 0.9995-0.9997,and the detection and quantification limits of three chloramphenicol drugs were 0.1 and 0.5 μg/kg, respectively. The 38 other drugs, including quinolones, sulfonamides, and nitro-imidazoles showed a linear relationship in the ranges of 2-200 μg/L with correlation coefficients of 0.9979-0.9999, and the detection and quantification limits of the 38 other drugs were 0.5 and 2.0 μg/kg, respectively. The recoveries of the 41 veterinary drugs at low, medium, and high spiked levels in chicken, pork, beef, and mutton samples were 80.0%-109.6%, with intra- and inter-day precisions of 0.3%-6.8% and 0.4%-7.0%, respectively. A total of 100 batches of animal meat (pork, chicken, beef, and mutton; 25 batches each) and known positive samples were simultaneously analyzed using the national standard method and the detection method established in this study. Sulfadiazine (89.2, 78.1, and 105.3 μg/kg) was detected in three batches of pork samples, and sarafloxacin (56.3, 102.0 μg/kg) was detected in two batches of chicken samples and no veterinary drugs were detected in the other samples; both methods yielded consistent results for known positive samples. The proposed method is rapid, simple, sensitive, environmentally friendly, and suitable for the simultaneous screening and detection of multiple veterinary drug residues in animal meat.

Combination of slow pathway late activation maps and voltage gradient maps in guidance of atrioventricular nodal reentrant tachycardia cryoablation

The optimal strategy for electroanatomic mapping-guided cryoablation of atrioventricular nodal reentry tachycardia (AVNRT) remains unclear. The purpose of this study was to investigate the effectiveness of slow pathway late activation mapping (SPLAM) and voltage gradient mapping for AVNRT cryoablation. From June 2020 to February 2022, all consecutive patients with AVNRT underwent SPLAM to define the wave collision point and voltage gradient mapping to define the low-voltage bridge (LVB). Conventional procedures performed from August 2018 to May 2020 served as control. The study and control groups comprised 36 patients (age 16.5 ± 8.2 years) and 37 patients (age 15.5 ± 7.3 years), respectively. Total procedural times were comparable, and acute success rates were 100% in both groups. Compared to controls, the number of cryomapping attempts (median 3 vs 5; P = .012) and cryoablation applications (median 1 vs 2; P <.001) were significantly lower in the study group. At median follow-up of 14.6 and 18.3 months, recurrence rates were 5.6% (2 patients) and 10.8% (4 patients) in the study and control groups (P = .402), respectively. Mapping of the Koch triangle took 11.8 ± 3.6 minutes, during which 1562 ± 581 points were collected. In SPLAM, wave collision points were defined and compatible with the final successful lesion sites in all patients, including those with multiple slow pathways. LVB could not be defined in 6 patients (16.7%), and LVB was not compatible with the final successful lesion in another 6 (16.7%). For AVNRT cryoablation, SPLAM could effectively guide the localization of slow pathway ablation sites and was particularly beneficial in patients with multiple slow pathways.

Ion Mobility-Mass Spectrometry Coupled to Droplet Microfluidics for Rapid Protein Structure Analysis and Drug Discovery.

Native mass spectrometry coupled to ion mobility (IM-MS) has become an important tool for the investigation of protein structure and dynamics upon ligand binding. Additionally, collisional activation or collision induced unfolding (CIU) can further probe conformational changes induced by ligand binding; however, larger scale screens have not been implemented due to limitations associated with throughput and sample introduction. In this work we explore the high-throughput capabilities of CIU fingerprinting. Fingerprint collection times were reduced 10-fold over traditional data collections through the use of improved smoothing and interpolation algorithms. Fast-CIU was then coupled to a droplet sample introduction approach using 40 nL droplet sample volumes and 2 s dwell times at each collision voltage. This workflow, which increased throughput by ∼16-fold over conventional nanospray CIU methods, was applied to a 96-compound screen against Sirtuin-5, a protein target of clinical interest. Over 20 novel Sirtuin-5 binders were identified, and it was found that Sirtuin-5 inhibitors will stabilize specific Sirtuin-5 gas-phase conformations. This work demonstrates that droplet-CIU can be implemented as a high-throughput biophysical characterization approach. Future work will focus on improving the throughput of this workflow and on automating data acquisition and analysis.

High stability tetradentate ligand copper complexes and organic small molecule hybrid electrolyte for dye-sensitized solar cells

A novel copper complex (CuL), where L is the tetradentate ligand 6,6-bis(pyridine-2-methoxy) methyl-2,2-pyridine, was designed and applied in dye-sensitized solar cells as a redox couple. Cyclic voltammetry demonstrates that the tetradentate ligand prompt CuL has excellent stability and that a ligand exchange reaction does not occur even in the presence of a high concentration of 4‑tert-butylpyridine, although ligand exchange reactions occur frequently with copper complexes containing bidentate ligands. Collision-induced dissociation mass spectrometry measures the collision voltage for the dissociation of the complexes, which is higher than for the traditional copper redox couple, indicating that these complexes have better stability than the traditional copper electrolytes have. Electrochemical impedance and open-circuit voltage delay indicate that the alkoxy chain of the ligand has excellent ability to inhibit photoelectron recombination, greatly prolonging the electron lifetime. The device based on this electrolyte achieved a short-circuit current density of 14.4 mA cm−2 and a photoelectric conversion efficiency of 9.1%. The hybrid electrolyte was obtained after being combined with organic small molecule TPAA; both Voc and Jsc of the device are improved, resulting in a 10.0% PCE for the device and maintained an initial efficiency of 96% after 800 h.

Toward Automation of Collision-Induced Unfolding Experiments through Online Size Exclusion Chromatography Coupled to Native Mass Spectrometry

Ion mobility (IM)-based collision-induced unfolding (CIU) has gained increasing attention to probe gas-phase unfolding of proteins and their noncovalent complexes, notably for biotherapeutics. CIU detects subtle conformational changes of proteins and emerges as an attractive alternative to circumvent poor IM resolution. However, CIU still lacks in automation for buffer exchange and data acquisition, precluding its wide adoption. We present here an automated workflow for CIU experiments, from sample preparation to data interpretation using online size exclusion chromatography coupled to native IM mass spectrometry (SEC-CIU). Online automated SEC-CIU experiments offer several benefits over nanoESI-CIU, among which are (i) improved and fast desalting compared to manual buffer exchange used for classical CIU experiments; (ii) drastic reduction of the overall data collection time process; and (iii) maintaining the number of unfolding transitions. We then evaluate the potential of SEC-CIU to distinguish monoclonal antibody (mAb) subclasses, illustrating the efficiency of our method for rapid mAb subclass identification at both intact and middle levels. Finally, we demonstrate that CIU data acquisition time can be further reduced either by setting up a scheduled CIU method relying on diagnostic trap collision voltages or by implementing mAb-multiplexed SEC-CIU analyses to maximize information content in a single experiment. Altogether, our results confirm the suitability of SEC-CIU to automate CIU experiments, particularly for the fast characterization of next-generation mAb-based products.

An Octanuclear Cobalt Cluster Protected by Macrocyclic Ligand: In Situ Ligand-Transformation-Assisted Assembly and Single-Molecule Magnet Behavior.

Macrocyclic molecules with multiple coordination sites have been widely used as promising ligands to build polynuclear metal clusters; however, cyclic silsesquioxane-based metal clusters are still rare. Herein, we report a new octanuclear Co-silsesquioxane cluster [Co8(OH)2{(MeSiO2)6}2(bpy)2(Obpy)2] (SD/Co8c; SD = SunDi), wherein the Co8 disc-like core is sandwiched by two hexamethylcyclohexasiloxanolate ligands (MeSiO2)6 at two poles and finally encircled by two bpy (bpy = 2,2'-bipyridine) and two Obpy (HObpy = 6-hydroxy-2,2'-bipyridine) ligands at the equatorial region. Interestingly, both MeSi(OMe)3 and bpy undergo in situ transformations to generate hexameric cyclic (MeSiO2)6 and Obpy, respectively. The unusual hydroxylation of bpy and the OH- anion in the center of Co8 core provide additional binding sites to induce the formation of the larger cluster instead of the traditional hexanuclear cluster. The solution stability and fragmentation route in the gas phase were studied by cold-spray ionization and collision-induced dissociation mass spectrometry, respectively. Both results reveal that the Co8 core is quite stable in solution as well as in the gas phase, even with increased collision voltage. Magnetic susceptibility studies of SD/Co8c show the slow magnetization relaxation indicative of single-molecule magnet (SMM) behavior. This work not only presents the multiple in situ ligand-transformation-assisted assembly of polynuclear cobalt cluster but also provides some new insights into the magnetism-structure relationship for SMMs.

Enhancement of multianalyte mass spectrometry detection through response surface optimization by least squares and artificial neural network modelling

In this work, the use of design of experiments and posterior data modelling by artificial neural network (ANN) and least squares (LS) is presented as a suitable analytical tool for the performance optimization of a tandem mass spectrometric detector coupled to ultra-high performance liquid chromatography for the analysis of seventeen veterinary drugs. Firstly, a central composite design was built considering as factors the cone, capillary, extractor and radio frequency voltages of the mass spectrometer in order to obtain a proper combination to improve the sensitivity of the method. Secondly, a one factor design considering the collision voltage was built to define the adequate voltage for each daughter ion. The response surface methodology (RSM) was then applied, and the prediction capability of ANN and LS were compared. As conclusion, the ANN modelling provided better results than LS, both in terms of the ANOVA and predicted areas results. The accuracy of the model prediction was between 85 and 125%, confirming that the estimates of the model were correct, and endorsing the optimization procedure as a suitable way to gather excellent results. The suitability of the new approach and its implications on the simultaneous analysis of seventeen veterinary drugs by ultra-high liquid chromatography coupled to tandem mass spectrometry detection are discussed.

Structural characterization of sulfur-containing aromatic compounds in heavy oils by FT-ICR mass spectrometry with a narrow isolation window

Detailed structural information on sulfur-containing aromatic compounds in heavy oils is valuable for the petroleum industry. In this work, Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) combined with collision-induced dissociation (CID) was applied to study the structures of sulfur-containing aromatic compounds in vacuum gas oil (VGO) and vacuum residue (VR). The parent ions of the sulfur-containing model compounds and high-sulfur heavy oils were isolated by the quadrupole in FT-ICR MS with a narrow isolation window of 1 Da. For most of the sulfur-containing model compounds, removal of S atoms was achieved in the collision voltage range 10–30 V. On the other hand, the removal of S atoms from the sulfur-containing compounds in heavy oils was restrained by optimization of the collision voltage. The structures of VGO and VR were also studied by CID FT-ICR MS with a narrow isolation window at the optimal collision voltages. The results suggested that naphtheno-aromatic sulfur-containing compounds were components of heavy oils and that the structural diversity of the heavy oils increased significantly with an increase in molecular weight.

MetaUniDec: High-Throughput Deconvolution of Native Mass Spectra.

The expansion of native mass spectrometry (MS) methods for both academic and industrial applications has created a substantial need for analysis of large native MS datasets. Existing software tools are poorly suited for high-throughput deconvolution of native electrospray mass spectra from intact proteins and protein complexes. The UniDec Bayesian deconvolution algorithm is uniquely well suited for high-throughput analysis due to its speed and robustness but was previously tailored towards individual spectra. Here, we optimized UniDec for deconvolution, analysis, and visualization of large data sets. This new module, MetaUniDec, centers around a hierarchical data format 5 (HDF5) format for storing datasets that significantly improves speed, portability, and file size. It also includes code optimizations to improve speed and a new graphical user interface for visualization, interaction, and analysis of data. To demonstrate the utility of MetaUniDec, we applied the software to analyze automated collision voltage ramps with a small bacterial heme protein and large lipoprotein nanodiscs. Upon increasing collisional activation, bacterial heme-nitric oxide/oxygen binding (H-NOX) protein shows a discrete loss of bound heme, and nanodiscs show a continuous loss of lipids and charge. By using MetaUniDec to track changes in peak area or mass as a function of collision voltage, we explore the energetic profile of collisional activation in an ultra-high mass range Orbitrap mass spectrometer. Graphical abstract ᅟ.

ORIGAMI: A software suite for activated ion mobility mass spectrometry (aIM-MS) applied to multimeric protein assemblies

We present here a software suite (ORIGAMI) that facilitates the rapid acquisition and analysis of ion mobility data following collisional activation. ORIGAMI was developed for use on Waters Synapt instruments where data acquisition is achieved by interfacing WREnS (Waters Research Enabled Software) and MassLynx. Two components are presented, the first is ORIGAMIMS which enables the activation of ions via a sequential ramping of collision voltage prior to ion mobility analysis. We demonstrate the use of ORIGAMI on the tetrameric assemblies formed by the proteins concanavalin A (103kDa) and alcohol dehydrogenase (143kDa). Activation is performed in the trap collision cell of the Synapt TriWave assembly where the collision voltage can be ramped from 0 to 200V. All of the acquired data is recorded in a single file which simplifies data acquisition while keeping the acquisition times at approx. 25min for a single charge state exposed to a collision voltage range of 0–200V. Following acquisition, the data are analysed in the second component, ORIGAMIANALYSE, which allows the user to visualise the effect of activation on the mobility of the parent ion, as well as on any fragment ion. The user can export the data in the form of heat maps, waterfall or wire plots as well as interactive and shareable webpages. In addition, tools implemented in ORIGAMI enable easy data extraction from single or multiple MassLynx .raw files, in-depth interrogation of large datasets, statistical analysis and figure creation capabilities.

Analysis of 8-hydroxy-2'-deoxyguanosine in human urine by ultra-high performance liquid chromatography mass spectrometer method

To develop an ultra-high performance liquid chromatography mass spectrometer method for the rapid determination of 8-hydroxy-2'-deoxyguanosine (8-OHdG) in human urines. 8-OHdG standard solution with the concentration from 0.01 to 0.1 μg/ml was formulated. The solution was implanted into ion source with a rate of 7 μl/min, the mass-to-charge ratio of parent ion and product ions, and ion mass to charge ratio was identified. The mass spectrum parameters of each Ion pairs, such as DP, EP and EXP, were gradually optimized. The urine sample with a concentration of 10.0 μg/L was detected, and the pH of the sample was adjusted using 1 mol/L ammonium formate and formic acid solution with a volume ratio of 5∶1, 4∶1, 3∶1, 2∶1, and 1∶1. It was tested using three different polarity of SPE, i.e.: HLB, MCX, and MAX. The elution effect of methanol and water mixture with the proportion of 90∶10, 80∶20, 50: 50, 20: 80, and 10: 90 were tested, and then acetonitrile and water mixture with the proportion of 90∶10, 80∶20, 50∶50, 20∶80, 10∶90 were also tested. The standard curve was constructed using the ratio of a standard series application fluid concentration to corresponding compounds quantitative ion liquid concentration of the peak area. The detection limit was determined as 3 times of the signal to noise ratio corresponding to the concentration of 8-OHdG, and the quantitative lower limit was determined as 10 times of the signal to noise ratio corresponding to the concentration of 8-OHdG. The blank urine spiked recovery method was used to evaluate the precision and recovery rate. The mass to charge ratio of parent ion was 284.1 and the product ions was 168.1, 140.1, 123.0, and 112.0, respectively. The collision voltage of quantitative ion-pair 284.1/168.1 was 18 V, the 284.1/140.1 collision voltage was 42 V, the 284.1/123.0 collision voltage was 48 V, and the 284.1/112.0 collision voltage was 53 V. The recovery rate was the highest (87.9%-104.3%) when the pH of urine was adjusted by a 10 ml 1 mol/L ammonium formate solution, 2 ml of formic acid, 88 ml of water are mixed with the sample solution volume ratio of 1∶5, and then purified with 3 ml of methanol and 3 ml water activated HLB extraction column. Within 1.0-100.0 μg/L concentration range, 8-OHdG standard application solution test results showed a good linear relationship. The regression equation was y= 1.25x+0.74, and the correlation coefficient was r=0.999 5. The detection limit was 0.2 μg/L, and the limit of quantification was 0.7 μg/L. The method of recovery rate was in the range of 87.9% to 104.3%, the precision was in the range from 1.5% to 3.7% and inter-assay precision was in the range from 1.6% to 5.4%. The method developed in this study had high sensitivity, good precision and accuracy, and a wide range of testing concentrations.

13C-assisted Ultra-High Performance Liquid Chromatography-Triple Quadrupole Mass Spectrometry Method for Precise Determination of Intracellular Metabolites in Pichia pastoris

Abstract The yeast Pichia pastoris is an effective host for recombinant protein production and the recombinant protein production level is tightly related to the concentrations of intracellular metabolites. The intracellular metabolites have the features of wide range of types, distinct variation in physical and chemical properties, rapid turning-over and low concentration, so it is difficult to quantify their concentrations precisely. In this study, we tried to make it possible by combining ultra-high performance liquid chromatography-triple quadrupole mass spectrometry method and 13 C isotope labeling techniques. 64 metabolites including organic acids, sugar phosphate, nucleoside substance, amino acid were successfully separated by UPLC with three kinds of chromatographic column. The appropriate and unique ion pairs and collision voltages were found after the mass spectrometry condition optimization. By using the U 13 C metabolites as internal standards collected from the cells growing on U 13 C-glucose as sole carbon source, the standard curves of 53 metabolites was established. The results showed that this method had a high accuracy. The correlation coefficients were above 0.99. The method also had a good reproducibility, and the influence of experimental and equipment operating condition was very small. Reliable and accurate determination of the concentrations of intracellular metabolites in Pichia pastoris was obtained. The works lays the foundation for comprehensive regulation mechanism research and efficient recombinant protein production in Pichia pastoris .

Can Nonpolar Polyisobutylenes be Measured by Electrospray Ionization Mass Spectrometry? Anion-Attachment Proved to be an Appropriate Method.

Polyisobutylenes (PIBs) with different end-groups including chlorine, exo-olefin, hydroxyl, and methyl prepared from aliphatic and aromatic initiators were studied by electrospray ionization mass spectrometry (ESI-MS). Independently of the end-groups, presence or absence of aromatic initiator moiety, these PIB derivatives were capable of forming adduct ions with NO3 (-) and Cl(-) ions, thus allowing the direct characterization of these compounds in the negative ion mode of ESI-MS. To obtain [PIB + NO3](-) and [PIB + Cl](-) adduct ions with appreciable intensities, addition of polar solvents such as acetone, 2-propanol, or ethanol to the dichloromethane solution of PIBs was necessary. Furthermore, increasing both the polarity (by increasing the acetone content) and the ion-source temperature give rise to enhanced intensities for both [PIB + NO3](-) and [PIB + Cl](-) ions. Energy-dependent collision induced dissociation studies (CID) revealed that increasing the collision voltages resulted in the shift of the apparent molecular masses to higher ones. CID studies also showed that dissociation of the [PIB + Cl](-) ions requires higher collision energy than that of [PIB + NO3](-). In addition, Density Functional Theory calculations were performed to gain insights into the nature of the interactions between the highly non-polar PIB chains and anions NO3 (-) and Cl(-) as well as to determine the zero-point corrected electronic energies for the formation of [PIB + NO3](-) and [PIB + Cl](-) adduct ions.

Structure, stability, and fragmentation of sodium bis(2-ethylhexyl)sulfosuccinate negatively charged aggregates in vacuo by MD simulations.

Negatively charged supramolecular aggregates formed in vacuo by n bis(2-ethylhexyl)sulfosuccinate (AOT(-)) anions and n + n(c) sodium counterions (i.e., [AOT(n) Na(n+nc)](nc)) have been investigated by molecular dynamics (MD) simulations for n = 1 to 20 and n(c) = -1 to -5. By comparing the maximum excess charge values of negatively and positively charged AOTNa aggregates, it is found that the charge storage capability is higher for the latter systems, the difference decreasing as the aggregation number increases. Statistical analysis of physical properties like gyration radii and moment of inertia tensors of aggregates provides detailed information on their structural properties. Even for n(c) = -5, all stable aggregates show a reverse micelle-like structure with an internal core, including sodium counterions and surfactant polar heads, surrounded by an external layer consisting of the surfactant alkyl chains. Interestingly, the reverse micelle-like structure is retained also in proximity of fragmentation. Moreover, the aggregate shapes may be approximated by elongated ellipsoids whose longer axis increases with n and |n(c)|. The fragmentation patterns of a number of these aggregates have also been examined and have been found to markedly depend on the aggregate charge state. The simulated fragmentation patterns of a representative aggregate show good agreement with experimental data obtained using low collision voltages.

Comparison of the activation time effects and the internal energy distributions for the CID, PQD and HCD excitation modes.

Reproducibility among different types of excitation modes is a major bottleneck in the field of tandem mass spectrometry library development in metabolomics. In this study, we specifically evaluated the influence of collision voltage and activation time parameters on tandem mass spectrometry spectra for various excitation modes [collision-induced dissociation (CID), pulsed Q dissociation (PQD) and higher-energy collision dissociation (HCD)] of Orbitrap-based instruments. For this purpose, internal energy deposition was probed using an approach based on Rice-Rampserger-Kassel-Marcus modeling with three thermometer compounds of different degree of freedom (69, 228 and 420) and a thermal model. This model treats consecutively the activation and decomposition steps, and the survival precursor ion populations are characterized by truncated Maxwell-Boltzmann internal energy distributions. This study demonstrates that the activation time has a significant impact on MS/MS spectra using the CID and PQD modes. The proposed model seems suitable to describe the multiple collision regime in the PQD and HCD modes. Linear relationships between mean internal energy and collision voltage are shown for the latter modes and the three thermometer molecules. These results suggest that a calibration based on the collision voltage should provide reproducible for PQD, HCD to be compared with CID in tandem in space instruments. However, an important signal loss is observed in PQD excitation mode whatever the mass of the studied compounds, which may affect not only parent ions but also fragment ions depending on the fragmentation parameters. A calibration approach for the CID mode based on the variation of activation time parameter is more appropriate than one based on collision voltage. In fact, the activation time parameter in CID induces a modification of the collisional regime and thus helps control the orientation of the fragmentation pathways (competitive or consecutive dissociations).

Differentiation of underivatized monosaccharides by atmospheric pressure chemical ionization quadrupole time‐of‐flight mass spectrometry

Differentiation of underivatized monosaccharides is essential in the structural elucidation of oligosaccharides which are closely involved in many life processes. So far, such differentiation has been usually achieved by electrospray ionization mass spectrometry (ESI-MS). As an alternative to ESI-MS, atmospheric pressure chemical ionization mass spectrometry (APCI-MS) should provide complementary results. A quadrupole time-of-flight (QTOF) mass spectrometer with accurate mass measurement ability was used with an APCI heated nebulizer ion source because we believe that a recently published article using a single quadrupole mass spectrometer assigned incorrect identities for APCI ions from hexoses. Using APCI-QTOF, the MS(2) and pseudo-MS(3) mass spectra of 11 underivatized monosaccharides were obtained under various collision voltages. The mass spectra were carefully interpreted after accurate mass measurement. Differentiation of three hexoses was achieved by different MS(2) spectra of their [M + NH(4)](+) and [M - H](-) ions. The MS(2) spectra of the [M + NH(4)](+) ions were also used to distinguish methyl α-D-glucose and methyl β-D-glucose, while the pseudo-MS(3) spectra of the [M + H](+) ions were utilized to differentiate the three hexosamine and N-acetylhexosamine stereoisomers. Unique [M + O(2)](-) ions were observed and their distinctive fragmentation patterns were utilized to differentiate the three hexosamine stereoisomers. Although ESI coupled with single or triple quadrupole and ion trap mass spectrometers has been widely utilized in the differentiation of monosaccharides, this report demonstrated that APCI-QTOF-MS had its own advantages in achieving the same goal.

A simple method to estimate relative stabilities of polyethers cationized by alkali metal ions

Dissociation of doubly cationized polyethers, namely [P + 2X](2+) into [P + X](+) and X(+), where P = polyethylene glycol (PEG), polypropylene glycol (PPG) and polytetrahydrofuran (PTHF) and X = Na, K and Cs, was studied by means of energy-dependent collision-induced dissociation tandem mass spectrometry. It was observed that the collision voltage necessary to obtain 50% fragmentation (CV(50)) determined for the doubly cationized polyethers of higher degree of polymerization varied linearly with the number of degrees of freedom (DOF) values. This observation allowed us to correlate these slopes with the corresponding relative gas-phase dissociation energies for binding of alkali ions to polyethers. The relative dissociation energies determined from the corresponding slopes were found to decrease in the order Na(+) > K(+) > Cs(+) for each polyether studied, and an order PPG ≈ PEG > PTHF can be established for each alkali metal ion.