Ion Enhancement Research Articles

Strategies for Using Postcolumn Infusion of Standards to Correct for Matrix Effect in LC-MS-Based Quantitative Metabolomics.

The matrix effect limits the accuracy of quantitation of the otherwise popular metabolomics technique liquid chromatography coupled to mass spectrometry (LC-MS). The gold standard to correct for this phenomenon, whereby compounds coeluting with the analyte of interest cause ionization enhancement or suppression, is to quantify an analyte based on the peak area ratio with an isotopologue added to the sample as an internal standard. However, these stable isotopes are expensive and sometimes unavailable. Here, we describe an alternative approach: matrix effect correction and quantifying analytes using a signal ratio with a postcolumn infused standard (PCIS). Using an LC-MS/MS method for eight endocannabinoids and related metabolites in plasma, we provide strategies to select, optimize, and evaluate PCIS candidates. Based on seven characteristics, the structural endocannabinoid analogue arachidonoyl-2'-fluoroethylamide was selected as a PCIS. Three methods to evaluate the PCIS correction vs no correction showed that PCIS correction improved values for the matrix effect, precision, and dilutional linearity of at least six of the analytes to within acceptable ranges. PCIS correction also resulted in parallelization of calibration curves in plasma and neat solution, for six of eight analytes even with higher accuracy than peak area ratio correction with their stable isotope labeled internal standard, i.e., the gold standard. This enables quantification based on neat solutions, which is a significant step toward absolute quantification. We conclude that PCIS has great, but so far underappreciated, potential in accurate LC-MS quantification.

Influence of carbon ionization increment by adding ne on the bonding, electrical, and tribological properties of carbon thin films deposited by HiPIMS

In this work, we use mass quadrupole spectroscopy to analyze the ion energy distribution function for C+ ions from different gas composition discharges (20, 40, 60, 80, and 90% Ne) + Ar in a plasma sputtering process. Carbon films were obtained for each gas composition discharge. The carbon bonding structure of films was analyzed by Raman spectroscopy using deconvolution fitting of the G and D Raman peaks. The C-sp3 content was correlated with the electrical and tribological properties of the carbon films. Our results further corroborate the enhancement of carbon ionization in HiPIMS processes by adding neon in conventional argon gas during the deposition process. Furthermore, we found that excessive levels of carbon ionization were detrimental in the formation of C-sp3 decreasing the resistivity, and indicating the decrement of the elastic modulus of the samples. In addition, the use of neon in the gas working mixture increased the deposition rate significantly compared to argon-only processes from 1.7 to 3.22 nm/min for the highest deposition rate cases. Tribology showed that an intermediate C-sp3 content in the carbon films developed desirable tribological behaviors with lower friction coefficients and wear rates, revealing that higher values of C-sp3 content are not necessarily for robust solid lubricious and wear resistance.

Low-Temperature Plasma Pretreatment Enhanced Cholesterol Detection in Brain by Desorption Electrospray Ionization-Mass Spectrometry Imaging.

Cholesterol is a primary lipid molecule in the brain that contains one-fourth of the total body cholesterol. Abnormal cholesterol homeostasis is associated with neurodegenerative disorders. Mass spectrometry imaging (MSI) technique is a powerful tool for studying lipidomics and metabolomics. Among the MSI techniques, desorption electrospray ionization-MSI (DESI-MSI) has been used advantageously to study brain lipidomics due to its soft and ambient ionization nature. However, brain cholesterol is poorly ionized. To this end, we have developed a new method for detecting brain cholesterol by DESI-MSI using low-temperature plasma (LTP) pretreatment as an ionization enhancement. In this method, the brain sections were treated with LTP for 1 and 2 min prior to DESI-MSI analyses. Interestingly, the MS signal intensity of cholesterol (at m/z 369.35 [M + H - H2O]+) was more than 2-fold higher in the 1 min LTP-treated brain section compared to the untreated section. In addition, we detected cholesterol, more specifically excluding isomers by targeted-DESI-MSI in multiple reaction monitoring (MRM) mode and similar results were observed: the signal intensity of each cholesterol transition (m/z 369.4 → 95.1, 109.1, 135.1, 147.1, and 161.1) was increased by more than 2-fold due to 1 min LTP treatment. Cholesterol showed characteristic distributions in the fiber tract region, including the corpus callosum and anterior commissure, anterior part of the brain where LTP markedly (p < 0.001) enhanced the cholesterol intensity. In addition, the distributions of some unknown analytes were exclusively detected in the LTP-treated section. Our study revealed LTP pretreatment as a potential strategy to ionize molecules that show poor ionization efficiency in the MSI technique.

Micro-sample Nd isotopic measurement on reference rock powders via the thermal ionization mass spectrometer Nd+ mode

The Sm–Nd isotopic system has been broadly utilized for dating and tracing in earth and planetary sciences. However, low Nd+ ionization efficiency permanently hinders precise and accurate measurements on small amounts of Nd samples. So far, isotopic measurement of micro-amount Nd sample via thermal ionization mass spectrometry (TIMS) Nd+ mode was mostly performed on Nd reference solutions, but less on natural rock or mineral samples. In the present study, analytical procedures to measure isotopic composition via the TIMS Nd+ mode were designed for natural rock powders by using 1–5 ng pure Nd. The analytical technique was refined through low-blank sample digestion, small-column chemistry for Nd extraction from matrix elements, loading Nd using purified H3PO4 solution, and careful heating of filaments before data acquisition. Measurements on small Nd amounts (1 ng–5 ng) of either the JNdi-1 reference solution or four reference rock powders yielded satisfactory results of 143Nd/144Nd value with respect to precision and accuracy. The analytical results agree well with the recommendation values of the reference materials within analytical errors and the internal precision is better than ±0.005 % (2RSE). When using 1 ng or 2 ng Nd amounts, 144Nd ion flow can remain stable in a signal intensity of >100 mV, and without the assistance of an additional ionization enhancer. Therefore, the analytical procedure, featured by low procedural blank (about 10–22 pg), high Nd+ ionization efficiency, and easy operation, has broad prospects for the application of Nd isotope in single-grain minerals or micro-samples.

Enhancement and suppression of nonsequential double ionization by spatially inhomogeneous fields

Using the three-dimensional classical ensemble approach, we theoretically investigate the nonsequential double ionization of argon atoms in an intense laser field enhanced by bowtie-nanotip. We observe an anomalous decrease in the double ionization yield as the laser intensity increases, along with a significant gap in the low momentum of photoelectrons. According to our theoretical analysis, the finite range of the induced field by the nanostructure is the fundamental cause of the decline in double ionization yield. Driven by the enhanced inhomogeneous field, energetic electrons can escape from the finite range of nanotips without returning. This reduces the possibility of re-scattering on the nucleus and imprints the finite size effect into the double ionization yield and momentum distribution of photoelectrons in the form of yield decline and a gap in the photoelectron-momentum distribution.

A validated dilute-and-shoot LC–MS-MS urine screening for the analysis of 95 illicit drugs and medicines: Insights from clinical and forensic Brazilian cases

Abstract Urine toxicological analysis is a relevant tool in both clinical and forensic scenarios, enabling the diagnosis of acute poisonings, elucidation of deaths, verification of substance use in the workplace and identification of drug-facilitated crimes. For these analyses, the dilute-and-shoot technique associated with liquid chromatography coupled with tandem mass spectrometry (LC–MS-MS) is a promising alternative since it has demonstrated satisfactory results and broad applicability. This study developed and validated a comprehensive LC–MS-MS screening method to analyze 95 illicit drugs and medicines in urine samples and application to clinical and forensic Brazilian cases. The dilute-and-shoot protocol was defined through multivariate optimization studies and was set using 100 µL of sample and 300 µL of solvent. The total chromatographic run time was 7.5 min. The method was validated following the recommendations of the ANSI/ASB Standard 036 Guideline. The lower limits of quantification varied from 20 to 100 ng/mL. Within-run and between-run precision coefficient of variations% were &amp;lt;20%, and bias was within ± 20%. Only 4 of the 95 analytes presented significant ionization suppression or enhancement (&amp;gt;25%). As proof of applicability, 839 urine samples from in vivo and postmortem cases were analyzed. In total, 90.9% of the analyzed samples were positive for at least one substance, and 78 of the 95 analytes were detected. The most prevalent substances were lidocaine (40.2%), acetaminophen (38.0%) and benzoylecgonine (31.5%). The developed method proved to be an efficient and simplified alternative for analyzing 95 therapeutic and illicit drugs in urine samples. Additionally, the results obtained from sample analysis are essential for understanding the profile of Brazilian substance use, serving as a valuable database for the promotion of health and safety public policies.

Research on ionization characteristics of atmospheric pressure pulse-modulated microwave He/air plasma jet

The atmospheric pressure pulsed microwave He plasma jet has the advantages of high electron density and abundant active particles, but its shrinking on the discharge electrode morphology limits its application range. In order to modulate a He plasma jet with a longer plume and study its ionization development characteristics, we constructed a dual-channel pulsed microwave coaxial discharge device. He and air were, respectively, injected into the inner and outer gas channels of the resonator to generate a double-layer atmospheric pressure microwave plasma jet with a longer plume. It is observed that the bifurcation of the stratified plasma jet will occur by changing the gas flow. The ionization development of plasma jet was observed by using enhanced charge-coupled device and microwave Rayleigh scattering apparatus measured the space-time evolution of plasma and observed the three times ionization enhancement process of plasma jet development. The spectral lines of the active products associated with Penning ionization were observed by using a fiber optic spectrometer. A fluid model was constructed to simulate and analyze that under the condition of sufficient He flow rate (He flow rate is above 0.6 slm), there will be sufficient and stable He mole fraction (64%) at the stratification of the plasma jet. The experimental and simulation results show that the jet profile of the microwave He plasma is related to the inlet structure of the discharger and He flow rate. Stratified intake structure can produce stratified He plasma jet, and the unique appearance of bifurcation of jet can be produced by changing the flow rate of He. In the bifurcation process of the plasma jet, the product of Penning ionization inhibits the development of the main branch of the plasma jet, and the secondary electron avalanche of the local electric field promotes the formation of the branch of the plasma jet and is accompanied by the enhancement of the second ionization. The ionization mechanism of microwave He plasma is the resonance excitation of local enhanced electric field, the advance of ionizing waves, and the interaction between the spatially distributed active particles.

Nitro Indole Derivatives as Novel Dual-Polarity Matrices for MALDI Mass Spectrometry and Imaging with Broad Applications.

A new matrix framework is presented in this study for the improved ionization efficiency of complex mixtures by matrix-assisted laser desorption ionization (MALDI) mass spectrometry/imaging. Five nitro indole (NI) derivatives [3-methyl-4-nitro-1H-indole (3,4-MNI), 3-methyl-6-nitro-1H-indole (3,6-MNI), 2,3-dimethyl-4-nitro-1H-indole (2,3,4-DMNI), 2,3-dimethyl-6-nitro-1H-indole (2,3,6-DMNI), and 4-nitro-1H-indole (4-NI)] were synthesized and shown to produce both positive and negative ions with a broad class of analytes as MALDI matrices. NI matrices were compared to several common matrices, such as 2,5-dihydroxybenzoic acid (DHB), alpha-cyano-4-hydroxylcinnamic acid (CHCA), sinapinic acid (SA), 1,5-diaminonaphthelene (1,5-DAN), and 9-aminoacridine (9-AA), for the analysis of lipid, peptide, protein, glycan, and perfluorooctanesulfonic acid (PFOS) compounds. 3,4-MNI demonstrated the best performance among the NI matrices. This matrix resulted in reduced ion suppression and better detection sensitivity for complex mixtures, for example, egg lipids/milk proteins/PFOS in tap water, while 2,3,6-DMNI was the best matrix for blueberry tissue imaging. Several important aspects of this work are reported: (1) dual-polarity ion production with NI matrices and complex mixtures; (2) quantitative analysis of PFOS with a LOQ of 0.5 ppb in tap water and 0.05 ppb in MQ water (without solid phase extraction enrichment), with accuracy and precision within 5%; (3) MALDI imaging with 2,3,6-DMNI as a matrix for plant metabolite/lipid identification with ionization enhancement in the negative ion mode m/z 600-900 region; and (4) development of a thin film deposition under/above tissue method for MALDI imaging with a vacuum sublimation matrix on a high-vacuum MALDI instrument.

Donor incomplete ionization and mobility enhancement in ultra-thin silicon-on-insulator films doped by phosphorus end-terminated polymers

The injection of P atoms is studied confining the same P dose in a progressively thinner silicon-on-insulator film. To account for the incomplete ionization observed in ultra-thin samples, the effect of Si/SiO2 interfaces must be considered.

Matrix effect in bioanalytical assay development using supercritical fluid chromatography-mass spectrometry.

Matrix effect (ME) is commonly caused by coelution of compounds with target analytes, resulting in either suppression or enhancement of analyte ionization. Thus, to achieve the desired accuracy, precision, and sensitivity, ME needs to be evaluated and controlled during bioanalytical method development. As the application of supercritical fluid chromatography-mass spectrometry (SFC-MS) for analysis of biological samples has increased, ME using SFC-MS has also been investigated with a focus on the difference in ME in SFC-MS compared to other chromatographic techniques used for achiral separation in biological samples. Here, we provide a summary of the status of ME evaluation and mitigation in SFC-MS methods. This review presents an overview of the phenomenon of ME and methods for evaluating ME in bioanalysis. Next, the factors that can impact ME in SFC-MS-based bioanalytical methods are discussed in detail with an emphasis on SFC. A literature review of the evaluation of ME in targeted bioanalytical methods using SFC-MS is included at the end. Robust instrumentation, effective sample preparation, and superb separation selectivity are the foundations of reliable analytical methods as well as the ability to mitigate detrimental ME in SFC-MS methods.

Influence of Thermionic Emission on He Ionization and Plasma Enhancement in Thermionic Energy Conversion

In this paper, the influence of thermionic emission on He ionization and plasma enhancement in thermionic energy conversion (TEC) are studied by experiment and numerical simulation. A 1D unsteady plasma TEC model, which includes a He ionization model, plasma conservation equations, and a thermionic emission formula for the wall, is developed. A He plasma thermionic energy conversion device composed of a barium–tungsten cathode and a tungsten anode is established. The volt–ampere curves of the He plasma TEC device are measured at 1050 K, 1150 K, 1250 K, 1300 K, and 1350 K temperatures. Both important cathode parameters, work function and emission area, are estimated. Based on the modelling simulation and the experiment, the He ionization mechanism in plasma TEC is discovered. The effects of cathode temperature on several distributions of plasma reaction rates, particle number density, and potential in He plasma TEC are described. Some important parameters, including electron mobility, resistivity, and plasma equilibrium are analyzed. The relationship of thermionic emission on plasma enhancement to the output power of plasma TEC is presented. The output powers of plasma TEC and vacuum TEC are compared at various cathode temperatures. A dimensionless analyzing method concerning thermionic emission intensity and plasma enhancement power is proposed. A brief dimensionless relationship is deduced regarding thermionic emission intensity and the plasma enhancement contribution of TEC. The principles and methods for quantitative calculations concerning the output power of plasma TEC under the action of thermionic emission are established. It is possible to do quantitative research on the effects of thermionic emission on plasma-enhanced TEC.

Reducing ion diffusion at atmospheric pressure through intermingled positive and negative ions

Increasing ion molecule reaction times for ambient ionization techniques can increase sensitivity of detection. Longer reaction times result in an increase in analyte signal relative to the reactant ion signal, however with a subsequent decrease in the total ion intensity. This loss in the total number of ions reaching the detector limits the extent to which increased reaction time can improve detection in practical applications. In this study ion loss was measured using either electric fields or gas flow to control ion transit time. Ion transit times ranged from 40 ms to 8 s, which resulted in ion densities ranging from 5 × 106 to 2 × 104 ions/cm3, respectively. These results provide insights into practical reaction time limitations or experimental boundaries when exploring sensitivity enhancements in ambient ionization. When exploring longer reaction times with an atmospheric flow tube coupled to a mass spectrometer (AFT-MS), an additional corona discharge ionization source of the same polarity was added in an attempt to increase total ion signal, but no improvement in signal was observed. This observation suggested that there was a maximum ion density being reached by the corona discharge that could not be increased by adding more of the same polarity ions. A hypothesis was that intermingling both polarities of ions would reduce ion loss and increase the measured ion signal. When two corona discharge sources—one each of positive and negative polarity—were used simultaneously in an AFT-MS, the total ion signal of either polarity measured by the MS was approximately double the current from a single corona discharge source. An increase in the negative ion signal was also observed when ∼10 parts-per-trillion vapor levels of an explosive (RDX, also known as hexogen) were introduced. In this case both the nitrate reactant ions and the RDX signal more than doubled with the addition of a corona discharge source producing positive ions. When intermingling positive and negative ions, an increase in ion current was also observed when the AFT was coupled directly to a Faraday detector or to an ion mobility spectrometer (IMS). This was the first demonstration of interfacing the AFT to an IMS. The observations and developments from this work will help in creating more portable instruments with improved sensitivity for detection of chemicals.

Desorption Kinetics Evaluation for the Development of Validated Desorption Electrospray Ionization-Mass Spectrometric Assays for Drug Quantification in Tissue Sections.

The development of desorption/ionization (DI) mass spectrometric (MS) assays for drug quantification in tissue sections and their validation according to regulatory guidelines would enable their universalization for applications in (clinical) pharmacology. Recently, new enhancements in desorption electrospray ionization (DESI) have highlighted the reliability of this ion source for the development of targeted quantification methods that meet requirements for method validation. However, it is necessary to consider subtle parameters leading to the success of such method developments, such as the morphology of desorption spots, the analytical time, and sample surface, to cite but a few. Here, we provide additional experimental data highlighting an additional important parameter, based on the unique advantage of DESI-MS on continuous extraction during analysis. We demonstrate that considering desorption kinetics during DESI analyses would largely help (i) reducing analytical time during profiling analyses, (ii) verifying solvent-based drug extraction using the selected sample preparation method for profiling and imaging modes, and (iii) predicting the feasibility of imaging assays using samples in a given expected concentration range of the targeted drug. These observations will likely serve as precious guidance for the development of validated DESI-profiling and imaging methods in the future.

A passive membrane system for on-line mass spectrometry reagent addition.

Post-separation addition of chemical modifiers in liquid chromatography-mass spectrometry is widely used for improving ionization sensitivity and selectivity. This is typically accomplished using a post-column T-junction, which can result in sample dilution and imperfect mixing. We present a passive semi-permeable hollow fiber membrane approach for the addition of chemical modifiers that avoids these issues. Model compounds were directly infused by flow injection to an electrospray ionization triple quadrupole mass spectrometer after passing through a polydimethylsiloxane hollow fiber membrane. Ionization enhancement reagents were introduced into the flowing stream by membrane permeation from aqueous solutions. Ionization enhancement from volatile acids and bases in positive and negative electrospray ionization was evaluated to assess the feasibility of this approach. The membrane-based apparatus resulted in relative ionization enhancement factors of up to 14×, depending upon the analyte, reagent, and ionization mode used. Ionization enhancement signal stability is reasonable (relative standard deviation of 5-7%) for extended periods from the same reagent solution, and minimal analyte dilution is observed. A proof-of-concept demonstration of the chromatographic "trifluoroacetic acid fix" strategy is presented. An on-line mass spectrometry ionization reagent addition method with potential post-chromatography reagent addition applications was developed using a hollow fiber polydimethylsiloxane membrane. This approach offers a promising alternative to traditional methods requiring additional hardware such as pumps and T-junctions that can result in sample dilution and imperfect reagent mixing.

3‐D Regional Imaging of Ionosphere Over Africa Through Assimilating Satellite and Ground‐Based Data

AbstractIn this study, the first high‐resolution regional ionospheric model over Africa and adjacent areas (−40–40°N latitude, 30°W–60°E longitude, and 80–1,400 km in altitude) is constructed by assimilating ground‐based slant total electron content (STEC) from 40 GPS (Global Positioning System) receiver stations and space‐based NmF2 (ionospheric F2 peak density) data from C2 (Constellation Observing System for Meteorology, Ionosphere, and Climate‐2) into the International Reference Ionosphere (IRI‐2016) model. An Ionospheric Data Assimilation Four‐Dimensional (IDA4D) technique was used to estimate electron densities as high as 1.5° 3° in latitude and longitude, 10 km in altitude in the E and F regions, and 15 min in universal time. Two experiments were run for the following data sets: (a) GPS‐STECs only and (b) GPS‐STECs and NmF2s from C2 during geomagnetically quiet (6–11 May 2021) and storm periods (12–14 May 2021). The IDA4D assimilation results are validated using independent C2 control group, ionosonde, and JASON‐3 observations. Results for the storm period show that experiment 2 reduces the average root‐mean‐square error (RMSE) of NmF2, foF2, and VTEC by 34%, 31%, and 34%, respectively, and increases the associated correlations by 10%, 14%, and 2% over IRI, respectively. Using IDA4D, we observed enhancement of the northern crest equatorial ionization anomaly in the late evening that was caused by upward and northward plasma transport.

Evaluation of Graphene Oxide as a Thermal Ionization Enhancer for Plutonium in TIMS Measurement.

Thermal ionization mass spectrometry (TIMS) has been extensively employed for the assessment of plutonium (Pu) isotopes in nuclear forensics and environmental monitoring. Recently, great efforts have been made to improve the ionization efficiency (IE) of Pu to achieve better accuracy and precision for trace-level analysis. Herein, the thermal ionization enhancement effect for plutonium of graphene oxide (GO) was investigated and the corresponding mechanism was discussed. The GO layers were homogeneously mounted on the filament's central surface to promote pg-level Pu ion emission. With the excellent structural property of GO, a greatly promoted ionization efficiency of 0.44% for Pu was obtained, and the initial ionization temperature for Pu was remarkably reduced from 1610 to 1390 °C. Average boosts in IE compared to the classical double-filament mode and graphite-loaded single-filament mode were 1640 and 520%, respectively. The analytical accuracy and precision based on the GO-loaded single-filament mode were validated using Pu isotopic certified reference materials. This work demonstrates the excellent property of GO as an ion source additive for Pu ionization, as it provided an interface for the promotion of energy transfer and Pu carbide formation. The operation of GO loading is quite simple and can be finished within 5 min. This rapid filament carburization approach has great potential for improving the measurement precision of trace-level plutonium isotopes and can be applied in nuclear safeguards, nuclear forensics, and environmental monitoring.

Atmospheric Effects of Magnetosheath Jets

We report effects in the upper high-latitude atmosphere related to the interaction of fast magnetosheath plasma streams, so-called jets, with the dayside magnetopause. The jets were observed by THEMIS mission in the dayside magnetosphere during a quiet day on 12 July 2009. It was found that the jet interaction was accompanied by strong localized compression and penetration of suprathermal magnetosheath plasma inside the dayside magnetosphere. The compression caused prominent magnetic variations with amplitudes up to 100 nT observed by ground-based magnetic networks SuperMAG and CARISMA. The magnetic variations were also visible in the geomagnetic Dst and AE indices. The jets also resulted in intense precipitation of the suprathermal ions with energies &lt; 10 keV and energetic electrons with energies &gt; 30 keV observed by low-altitude NOAA/POES satellites in a wide longitudinal range. The precipitations produced enhancements of ionization with an amplitude of ~1 TECU (~30% in relative units) and intensification of the ionospheric E and F1 layers as observed in the FORMOSAT-3/COSMIC misson. The enhanced ionization in the upper atmosphere might affect radio communication and navigation in the high-latitude regions. These results also provide new insight into the contribution of magnetospheric forcing to day-to-day ionospheric variability.

Ionization waves in low-current dc discharges in noble gases obtained with a hybrid kinetic-fluid model.

A hybrid kinetic-fluid model is used to study ionization waves (striations) in a low-current plasma column of dc discharges in noble gases. Coupled solutions of a kinetic equation for electrons, a drift-diffusion equation for ions, and a Poisson equation for the electric field are obtained to clarify the nature of plasma stratification in the positive column. A simplified two-level excitation-ionization model is used for the conditions when the nonlinear effects due to stepwise ionization, gas heating, and Coulomb interactions among electrons are negligible. It is confirmed that the nonlocal effects are responsible for the formation of moving striations in dc discharges at low plasma densities and low values of pR (the product of gas pressure and tube radius). The calculated properties of self-excited waves of S-, P-, and R types in neon and S type in argon agree with available experimental data. The reason for helium plasma stability to stratification is clarified. It is shown that sustaining stratified plasma is more efficient than striation-free plasma when the ionization rate is a nonlinear function of the electric field. However, the nonlinear dependence of the ionization rate on the electric field is not required for plasma stratification. Striations of S-, P-, and R types in neon exist with minimal or no ionization enhancement. Effects of the column length and plasma density on the wave properties are demonstrated.

LC–MS/MS method for simultaneous quantification of ten antibiotics in human plasma for routine therapeutic drug monitoring

BackgroundOptimizing antimicrobial therapy to attain drug exposure that limits the emergence of resistance, effectively treats the infection, and reduces the risk of side effects is of a particular importance in critically ill patients, in whom normal functions are augmented or/and are infected with pathogens less sensitive to treatment. Achievement of these goals can be enhanced by therapeutic drug monitoring (TDM) for many antibiotics. A liquid chromatography tandem mass spectrometry (LC–MS/MS) method is presented here for simultaneous quantification of ten antimicrobials: cefazolin (CZO), cefepime (CEP), cefotaxime (CTA), ceftazidime (CTZ), ciprofloxacin (CIP), flucloxacillin (FLU), linezolid (LIN), meropenem (MER), piperacillin (PIP) and tazobactam (TAZ) in human plasma. MethodsPlasma samples were precipitated with acetonitrile and injected into the LC–MS/MS. Chromatographic separation was on a Waters Acquity BEH C18 column. Compounds were eluted with water and acetonitrile containing 0.1 % formic acid, using a gradient (0.5–65 % B), in 3.8 min. The flow rate was 0.4 mL/min, and the run time was 5.8 min. ResultsThe calibration curves were linear across the tested concentration ranges (0.5–250, CZO, CEP, CTA, CTZ and FLU; 0.2–100, MER and TAZ; 0.1–50, CIP and LIN and 1–500 mg/L, PIP). The intra and inter-day imprecision was < 11 %. Accuracy ranged from 95 to 114 %. CTZ and MER showed ionization suppression while CIP showed ionization enhancement, which was normalized with the use of the internal standard. ConclusionAn LC–MS/MS method for simultaneous quantification of ten antimicrobials in human plasma was developed for routine TDM.

The effect of magnet core size on the performance of a cylindrical Hall thruster with the near-anode cusp magnetic field

Effect of magnet core size on the performance of a cylindrical Hall thruster with the near-anode magnetic field has been investigated. Experiments found that extending magnetic core and rising discharge voltage show similar effects on the ionization process. When the magnetic core ends flush with the anode and discharge voltage is fixed at 240 V, the upstream ionization related with the electron E × B drift is hardly established under an approximately axial magnetic field and the ionization region is located at the near-axial magnetic mirror field, the thruster manifests the highest propellant utilization efficiency (as high as 1.43), the lowest current utilization efficiency (0.54) and beam divergence efficiency (0.52). When the magnet core extends towards the thruster exhaust, the enhancement of upstream ionization results in significant enhancements in the current utilization efficiency (by 14.6%) and the beam divergence efficiency (by 27.1%). However, the reduction of magnetic mirror ionization also led to a reduction of propellant utilization efficiency (by 32.1%). Therefore, the anode efficiency varies non-monotonically (climbing up and then declining) and has an optimal solution: shorter magnet core performs higher anode efficiency in low voltage condition and longer magnet core performs higher anode efficiency in high voltage condition.