流动注射-电感耦合等离子体质谱法的基体效应

研究了流动注射小体积进样,电感耦合等离子体质谱法的在体效应,并与连续进样作了比较,流动注射小体积（１００μＬ）进样时,电离电位较高的Ａｓ和Ａｕ基体对分析元素的信号表现为增强效应,分析元素的质量数越大,所受增强效应越小。了电位较低的Ｃｕ、Ｉｎ、Ｌｉ、Ｎａ和Ｐｂ基体对分析元素的信号则表为抑制效应,基体元素的质量数越大,对分析元素的抑制效应也越大;质量数较大的分析元素,所受的抑制效应较;对质量数相近的分析元素,电离电位较高者受的抑制较大,与连续进样相比,流动注射小体积进样时,基体元素对分析元素的抑制效应较弱,而增强效应较强。     

Signal suppression/enhancement in HPLC-ESI-MS/MS from concomitant medications

This paper presents a study of the signal suppression and enhancement effects in assays based on HPLC-ESI-MS/MS detection. The major focus was to investigate the effect of signal suppression/enhancement of typical co-administered (concomitant) medications, i.e. naproxen and ibuprofen. The results demonstrate that the analyte and internal standard can experience signal enhancement up to a factor of ca 2.9 if the test analyte or internal standard co-elute with concomitant. Experimental results also demonstrate that the analyte and internal standard signal increased by a factor of ca 2.0 in the negative ion mode at physiological relevant levels of naproxen (100 microg/mL) and by a factor of ca 1.6 in the negative ion mode at physiological relevant level of ibuprofen (10 microg/mL) in both neat and plasma samples. Signal enhancement significantly increased when concomitant medications ionized in the same ion mode as the analyte and internal standard. To overcome signal enhancement or potential suppression from concomitant medications, a comprehensive HPLC method needs to be developed with sufficient separation of concomitant medication from the analyte and internal standard. Other means to reduce signal enhancement or potential suppression include switching ionization polarity and performing comprehensive sample clean-up to remove concomitant medications before analysis.     

Charge assisted laser desorption/ionization mass spectrometry of droplets

We propose and evaluate a new mechanism to account for analyte ion signal enhancement in ultraviolet-laser desorption mass spectrometry of droplets in the presence of corona ions. Our new insights are based on timing control of corona ion production, laser desorption, and peptide ion extraction achieved by a novel pulsed corona apparatus. We demonstrate that droplet charging rather than gas-phase ion-neutral reactions is the major contributor to analyte ion generation from an electrically isolated droplet. Implications of the new mechanism, termed charge assisted laser desorption/ionization (CALDI), are discussed and contrasted with those of the laser desorption atmospheric pressure chemical ionization method (LD-APCI). It is also demonstrated that analyte ion generation in CALDI occurs with external electric fields about one order of magnitude lower than those needed for atmospheric pressure matrix assisted laser desorption/ionization or electrospray ionization of droplets.     

Matrix‐enhanced secondary ion mass spectrometry: the influence of MALDI matrices on molecular ion yields of thin organic films

In this work the effect in secondary ion mass spectrometry (SIMS) of several frequently used matrix‐assisted laser desorption/ionisation (MALDI) matrices on the secondary ion intensities of low molecular weight (m/z 400–800) organic dyes and a pharmaceutical is tested. Matrix (10^?1 M) and analyte (10^?2 M) solutions were made in methanol. Mixtures with several concentration ratios were prepared from these solutions and spincoated on Si substrates prior to time‐of‐flight (TOF)‐SIMS analysis. In some cases the presence of the MALDI matrices caused a considerable increase in the positive secondary (protonated) molecular ion signals. Enhancements of a factor of 20 and more were recorded. Generally, of the matrices used, 2,5‐dihydroxybenzoic acid and 2,4,6‐trihydroxyacetophenone brought about the highest intensity increases. It was also shown that matrix‐enhanced (ME‐)SIMS is capable of lowering the detection limits for molecule ions. However, the enhancement effect is strongly influenced by the analyte/matrix combination and its concentration ratio. As a result, finding an optimal analyte/matrix mixture can be a very time‐consuming process. Mostly, the presence of the matrices causes changes in the relative ion intensities in the TOF‐S‐SIMS spectra. Compared to the spectra recorded from samples without matrices, only a few additional peaks, such as signals that originate directly from the applied matrix or adduct ions, are observed in the mass spectra. Sometimes molecule ions and some characteristic fragments at high m/z values, that cannot be recorded without matrix, do appear in the spectrum when a matrix is present. In the negative mode no enhancement effect is observed on applying the studied MALDI matrices. The results obtained from samples treated with MALDI matrices are also compared to SIMS results for the same samples after Ag and Au metallisation (MetA‐SIMS). For three of the four tested compounds Au MetA‐SIMS resulted in higher ion yields than ME‐SIMS. For both techniques possible mechanisms that can account for the enhancement effect are proposed. Copyright © 2005 John Wiley & Sons, Ltd.     

The effect of easily ionizable concomitant elements on non-spectroscopic interferences in inductively coupled plasma-mass spectrometry

Reported are the effects of easily ionizable concomitant elements on non-spectroscopic interferences in ICP-MS. Analyte ion suppression was studied for ⁷Li, ¹¹B, ⁵⁸Ni, ⁴⁵Sc, ⁸⁹Y and ²⁰⁵Tl in the presence of concomitant elements spanning a mass range from 23 (Na) to 207 (Pb) dallons.For the analytes studied, it was found that the greater the atomic mass of the concomitant element, the greater was the analyte ion count rate suppression. For a given set of experimental conditions, the greater the atomic mass of the analyte, the lower was its susceptibility to ion count rate suppression by any concomitant element.The severity of non-spectroscopic interferences decreased as the sampler orifice was positioned further away from the center of the plasma and also as the sampling depth was increased. Dilution of a solution containing a given molar ratio of concomitant to analyte reduced the extent of analyte ion suppression.Non-spectroscopic interferences in ICP-MS can be attributed to ambipolar diffusion effects in the plasma that result from the presence of easily ionizable concomitant elements.     

Using surfactants to enhance the analyte signals in activated carbon, surface-assisted laser desorption/ionization (SALDI) mass spectrometry

The effect of surface activity in surface-assisted laser desorption/ionization (SALDI) mass spectrometry was examined. Several surfactants, including p-tolunensulfonic acid (PTSA), sodium dodecyl sulfate and alkyltrimethylammonium bromide, were used as analytes or additives in the SALDI matrix to demonstrate the surface activity effect. The experimental results demonstrate that analytes that have good surface activity have good sensitivity. Adding suitable amounts of surfactants to the SALDI matrix can dramatically enhance the sensitivity of analytes lacking surface activity. We propose that the enhancement of analyte signals is due to the ionic interaction between ionic surfactants and analytes because non-ionic surfactant additives in the SALDI matrix do not affect the analyte signals. The detection limit of methylephedrine can be as low as 100 pg in the SALDI analysis of 0.5 M PTSA additive in the SALDI matrix. Although other surfactants can also be used as matrix additives to enhance the analyte signal, they do not improve the ion abundance as much as PTSA does.     

A comparative study of a liquid and a solid matrix in matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and collision cross section measurements

We present experimental matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) results comparing a liquid (glycerol/K(4)[Fe(CN)(6)]) and a solid matrix (2,5-dihydroxybenzoic acid, DHB) with respect to analyte signal stability and initial ion velocity. For applications requiring stable production of analyte ions over a long period of time, the liquid matrix is superior to the solid matrix. The stable analyte ion signal obtained from a liquid matrix allowed the measurement of collision cross sections of small poly(ethylene glycol) (PEG(n)) adduct ions in the flight tube with good resolution. The initial velocity of these adduct ions was measured. It was found that analyte molecules from the liquid matrix have initial ion velocities significantly smaller than those from the solid matrix. MALDI-TOF measurements for large molecules using a liquid matrix are therefore likely to result in smaller systematic errors in mass calibrations due to initial ion velocity.     

Mesoporous tungsten titanate as matrix for matrix-assisted laser desorption/ionization time-of-flight mass spectrometry analysis of biomolecules

In this paper, mesoporous tungsten titanate (WTiO) with different nano-pore structures was utilized as matrix for the analysis of short peptides by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOFMS). Effect of characteristic features of mesoporous matrices on laser desorption/ionization process was investigated. Experiments showed that the ordered two-dimensional and three-dimensional mesoporous matrices were superior in performance to the non-ordered WTiO matrix. The dramatic enhancement of signal sensitivity by the ordered mesoporous matrices can be reasonably attributed to the ordered structure, which facilitated the understanding on structure-function relationship in mesoporous cavity for laser desorption process of adsorbed biomolecules. With the ordered mesoporous matrix, the short peptides are successfully detected. The presence of trace alkali metal salt effectively increased the analyte ion yields and the MALDI-TOFMS using the inorganic mesoporous matrices displayed a high salt tolerance. The developed technique also showed a satisfactory performance in peptide-mapping and amino-acid sequencing analysis.     

Volatile organic solvent-induced signal enhancements in inductively coupled plasma-mass spectrometry: a case study of methanol and acetone

Methanol and acetone were used to study effects of organic matrix on signal intensities of elements from ⁷Li to ²³⁸U and oxide yields in inductively coupled plasma-mass spectrometry (ICP-MS). Enhancement or suppression of analyte signals in the presence of methanol or acetone depends on the volatility and concentration of the compound and mass and ionization potential of elements concerned as well as ICP-MS operating conditions. Presence of a low concentration of methanol or acetone enhances the intensities of elements in order of decreasing mass. This is attributed to the spatial shift of the zone of maximum ion density, which, in turn, affects the extraction of ions from the plasma to the sampling cone. The possible effect of liquid methanol or acetone on nebulization and/or transport efficiency was avoided by using carry-over effect experiment. More volatile acetone more readily suppresses signals of all the elements under investigation. A higher concentration of methanol also suppresses intensities of the elements due to resultant cooling of the plasma. The enhancement effect of methanol and acetone appears to be more related to the amount of carbon present in the plasma than the difference between the functional groups of organic solvents. The oxide yield decreases in the presence of methanol, the magnitude of which depends on the nebulizer gas flow rate used. However, the reduced oxide yield is insufficient to account for the signal enhancement. Our results for ⁷⁵As and ⁷⁸Se agree with the C⁺-species–analyte atom charge transfer reaction hypothesis.     

Signal suppression/enhancement in high-performance liquid chromatography tandem mass spectrometry

The review discusses the pitfalls of the matrix effect in mass spectrometry detection hyphenated to liquid chromatography separation. Matrix effect heavily influences both qualitative and quantitative analyses, giving rise to suppression or enhancement of the signal. As generally recognised, the predominant cause is the presence of undesired components that co-elute in the chromatographic separation and alter the ionisation process. The interfering species can be components of the sample, compounds released during the pre-treatment/extraction process or reagents added to the mobile phase to improve chromatographic resolution. The different mechanisms proposed in literature to explain the suppression or the enhancement of the signal both in electrospray and atmospheric pressure chemical ionisations are presented and the results observed in the different experimental conditions are compared and discussed. All data together lead to conclude that the chemical properties of the target analyte, the kind of matrix, the matrix to analyte concentration ratio, the extraction process, the chromatographic conditions as well as the kind of the mass spectrometry instrumentation and the ionisation conditions can play a role. Likely all these potential causes act in a synergic way and the final effect observed is hardly due to only one of them. Depending on an unpredictable combination of conditions, signal suppression or enhancement can be observed. The review discusses the matrix effects observed in HPLC–MS and HPLC–MS/MS analysis proposes hypotheses to explain the observed behaviours and proposes methods and strategies to overcome the matrix effects.     

Determination of perfluorochemicals in biological, environmental and food samples by an automated on-line solid phase extraction ultra high performance liquid chromatography tandem mass spectrometry method

A rapid on-line solid phase extraction ultra high performance liquid chromatography tandem mass spectrometry method was developed for the identification and quantitation of nine perfluorinated compounds in matrices of environmental, biological and food interest. Pre-treatment, solid phase extraction, chromatographic and mass detection conditions were optimised, in order to apply the whole methodology to the analysis of different matrices. Particular attention was devoted to the evaluation of matrix effect and the correlated phenomena of ion enhancement or suppression in mass spectrometry detection. LOD and LOQ range from 3 to 15ngL(-1) and from 10 to 50ngL(-1), respectively. Method detection limits (MDLs) were also calculated for each kind of matrix. The recovery, evaluated for each analyte, does not depend on analyte concentration in the explored concentration range: average Rˉ% values are always greater than 82.9%. In the whole, the results obtained for samples of river waters, blood serum, blood plasma, and fish confirm the ubiquitous presence of perfluorinated compounds, as recently denounced by many sources.     

N-Alkylnicotinium halides: A class of cationic matrix additives for enhancing the sensitivity in negative ion Fast-Atom bombardment mass spectrometry of polyanionic analytes

The addition of some surfactants to the fast-atom bombardment (FAB) matrix previously has been demonstrated to enhance analyte signals in fast-atom bombardment mass spectrometry. In particular, cationic surfactants appear to enhance the negative ion FAB detectability of analytes that exist as anionic species in the matrix solution. It has been proposed that the charged surfactant concentrates the oppositely charged analyte near the surface, which results in larger signals for the analyte. Cationic surfactants that contain a fixed positive charge and an additional basic site were prepared with different hydrophobic moieties and were evaluated for their effectiveness as FAB matrix additives. The compound N-octylnico-tinium bromide (ONBr) is shown to improve greatly the analyte-related signals in negative ion fast-atom bombardment mass spectrometry for a variety of polyanionic analytes, relative to other surfactants (e.g., cetylpyridinium salts). This surfactant not only enhances detectability, but also simplifies the pseudomolecular ion region of the resulting spectra by reducing or eliminating metal cation adduct peaks. The simple mechanism of enhancement via surface activity is evaluated, and alternative mechanisms are considered. It is clearly shown that ONBr, as a FAB matrix additive, will allow mass spectrometry to be used for the analysis of anionic compounds that normally exhibit very low responses.     

Evaluation of the interrelationship between mass resolving power and mass error tolerances for targeted bioanalysis using liquid chromatography coupled to high‐resolution mass spectrometry

The determination of acceptable mass error tolerances for high‐resolution mass spectrometry based signals has been evaluated in a comprehensive way. This was achieved by using a technical approach which is based on the post‐column infusion of an analyte containing solution. This well‐known experimental setup was not used to spot signal suppression regions of a particular analyte, but to spot regions of the chromatogram where a systematic mass drift of the analyte ion can be observed (isobaric interference plot). Not the changing signal intensity but the stability of the measured analyte mass was observed. A wide range of different analytes in combinations with potentially interfering matrices has been evaluated. Furthermore, different mass resolving power settings were evaluated. Isobaric interferences between matrix compounds and analytes were common at mass resolving powers <50 000 full width at half maximum. The proposed post‐column infusion technique is a useful tool for the determination of the assay and matrix‐specific mass error tolerances. It aims to ensure the highest possible selectivity, at the same time preventing the encounter of detrimental mass error related peak deformations as well as false negative findings. Unlike conventional matrix spiking approaches, isobaric interference plots provide information of potential interferences across the whole chromatographic time range. This becomes relevant when there is a relative retention time shift between the analyte and potential interfering matrix compounds. Furthermore, the described setup can be used to study how the mass accuracy of any mass spectrometer is affected by a widely varying total ion current. Copyright © 2012 John Wiley & Sons, Ltd.     

Effect of cocrystallization due to bile acid on molecular-ion sensitivity of biological phospholipids in Bi cluster time-of-flight secondary ion mass spectrometry measurements

Bi cluster time-of-flight secondary ion mass spectrometry (TOF-SIMS) is a useful method for evaluating organic surfaces. However, its ability to detect large molecules is limited. One of the problems is that the sensitivities of macromolecules are lower than those of small molecules because larger molecules tend to exhibit lower ionization efficiencies and/or higher probabilities of fragmentation. Matrix-enhanced (ME)-SIMS is a sensitivity enhancement technique for intact molecular ions. The crystal structure of a mixed substance composed of an analyte and a matrix is known to affect the sensitivity of the analysis target. In this study, the effect of cocrystallization, which occurs due to the presence of bile acid, on the molecular-ion sensitivity was investigated using Bi cluster TOF-SIMS. Biological phospholipids and bile acids, which exhibit surfactant behaviors, were selected as the evaluated molecules and additives, respectively. The mass spectra indicated that the secondary-ion yields of phospholipids with bile acid were substantially greater than those of the pristine lipid. Specifically, samples with an analyte/bile acid ratio of 1:100 achieved approximately 60–100-fold sensitivity enhancement of [M + H]⁺ and [2M + H]⁺ molecular ions than the sensitivity achieved with the pristine samples. In the evaluation of molecular distribution, higher signal counts of intact ions were obtained from the cocrystallization area, although less-fragmented ions were emitted from these regions. Consequently, the results indicate that the cocrystallization due to the presence of bile acid provides an effective crystal structure for facilitating emission of larger molecules.     

Segmented post-column analyte addition; a concept for continuous response control of liquid chromatography/mass spectrometry peaks affected by signal suppression/enhancement

A novel technique, "segmented post-column analyte addition", is proposed to visualize and compensate signal suppression/enhancement effects in electrospray ionization tandem mass spectrometry (ESI-MS/MS). Instead of delivering a constant flow of analyte solution between the liquid chromatography (LC) column exit and the ESI interface into the eluent resulting from LC separation of analyte-free matrix in order to determine retention time widows in which suppression/enhancement is unimportant (King et al., J. Am. Soc. Mass Spectrom. 2000; 11: 942), segmented packets of analyte-containing solvent and analyte-free solvent were infused into an LC eluent resulting from separation of an analyte-containing sample. The obtained, superimposed, periodic spikes are much narrower than the analyte peak eluting from the column. The height of the spikes is affected by signal suppression phenomena to the same extent as the analyte signal, and hence variations of the spike height can be used to correct the peak area of analyte peaks affected by signal suppression/enhancement.     

Suppression and enhancement of secondary ion formation due to the chemical environment in static-secondary ion mass spectrometry

Through analyzing mixtures of compounds of known gas-phase basicities, the importance of this property on the secondary ions emitted from a surface under primary ion bombardment is investigated. The aim is to obtain a greater understanding of the ionization mechanisms that occur in secondary ion mass spectrometry (SIMS). The commonly used matrix assisted laser desorption/ionization (MALDI) matrix 2,4,6-trihydroxyacetophenone (THAP) and a range of low molecular weight biomolecules were used to investigate whether analyte/matrix suppression effects that have been observed in analogous MALDI experiments were also present in static-SIMS. The outcome of the experiments demonstrates that strong suppression of the quasi-molecular signal of one molecule in a mixture can occur due to the presence of the other, with the gas-phase basicity of the compounds being a good indicator of the secondary ions detected. It is also demonstrated that the suppression of the quasi-molecular ion signal of a compound in a two-component mixture can be minimized by the inclusion of a third compound of suitable gas-phase basicity.     

Time-resolved measurements of individual ion cloud signals to investigate space-charge effects in plasma mass spectrometry

A new approach to directly monitor space charge induced effects due to high concentrations of efficiently ionized elements in inductively coupled plasma mass spectrometry (ICP-MS) is described. The broadening of ion clouds produced from individual, monodisperse drops of sample is measured by using time-resolved ICP-MS. The extent of broadening due to high concentrations of Pb in the sample is related inversely to the analyte mass. For the lightest analyte investigated, Li⁺, the relative width of the time-resolved analyte peak increases and then shows a dip in the center as the Pb concentration is increased to 500 and then 1500 µg/mL. The initial results of experiments that investigated chemical matrix effects as a function of concomitant species concentration, analyte mass, and sampling location in ICP-MS are consistent with space-charge effects.     

Reduction of matrix effects in ICP-MS by optimizing settings of ion optics

The effect of ion optics settings on the degree of suppression of analyte signals due to the presence of different basic elements in a sample solution, such as manganese, copper, indium, lanthanum, hafnium, and lead, was investigated on an example of an XSeries II inductively coupled plasma mass spectrometer. The effect of atomic mass and the concentration of the matrix element on the optimum values of ion optics settings and the change in the analyte signals was studied. It was shown that a decrease in the potential of the extractor lens to ?300 V can significantly reduce the matrix effect. As an example, the results of determining impurity elements in solutions containing up to 1 g/L of lanthanum were obtained using standard settings of the spectrometer with a reduced voltage on the extractor. It was shown that the optimization of ion optics settings enables the use of more concentrated solutions, thus reducing the detection limits for elements by several times.     

Spatially resolved measurements of ion density behind the skimmer of an inductively coupled plasma mass spectrometer

Ions are extracted from the inductively coupled plasma through a conventional sampler and skimmer and then deposited on an array of graphite targets at the exit of a set of electrostatic ion lenses. The Sc⁺ signal is enhanced by choosing appropriate potentials on the ion lenses. The Sc⁺ signal is suppressed by the presence of concomitant Cs ions at high concentrations. Comparisons of grounded ion lenses and two different ion lens potential settings are made. The signal is enhanced more extensively by the ion lenses when there are no concentrated concomitant ions. This study indicates that matrix effects in inductively coupled plasma mass spectrometry could possibly be alleviated by choosing ion lens potentials such that the ions enter the ion optics with a relatively broad beam cross section, the beam then being focused to a smaller size. A photon stop inside the ion lens stack reduces ion transmission and changes the shape of the beam profile from conical to bimodal.     

Approaches to sample pretreatment in the determination of perchlorate in real world samples

Perchlorate can be determined by the tandem technique of ion chromatography (IC) coupled to electrospray ionization mass spectrometry (ESI-MS). However, detection by ESI-MS can be compromised by the coelution of matrix components that can suppress the analyte signal. In addition, the presence of surface-active and other types of matrix components can cause fouling of the electrospray inlet, reducing overall signal and requiring frequent maintenance. The influences of matrix components can be minimized by using analytical columns with different selectivities, in-line diversion of separated matrix components, and off-line selective removal of matrix components via ion exchange or adsorption. This paper will discuss these sample preparation approaches for samples containing anionic species including surfactants and inorganic ions that elute in the vicinity of perchlorate.