Near‐field laser ablation inductively coupled plasma mass spectrometry: a novel elemental analytical technique at the nanometer scale

An analytical technique utilizing a near‐field effect (to enhance the incident light energy on the thin tip of an Ag needle) in a laser ablation inductively coupled plasma mass spectrometry (NF‐LA‐ICP‐MS) procedure was developed. To produce the thin needles with a tip diameter in the hundreds of nm range a robust needle etching procedure was established. The ‘sample‐to‐tip’ distance was controlled via the measurement of a tunnel current between the needle and sample surface. The NF‐LA‐ICP‐MS technique thus developed was applied for the analysis of copper isotopic standard reference material NIST SRM 976 and tungsten‐molybdenum alloy NIST SRM 480 in the nm resolution range. The observed craters ranged from 200 nm to about 2 µm in diameter and were dependent on the needle used as well as on the ‘sample‐to‐tip’ distance. The mass spectrometric measurements of ⁶³Cu⁺ ion intensity on NIST SRM 976 showed that using near‐field enhancement in laser ablation allowed a roughly 6‐fold increase in the ion intensity of the analyte when the needle was about 100 nm (and below) from the surface, in contrast to when it was far away (e.g. 10 µm) from the sample. The relative standard deviation (RSD) of the ⁶⁵Cu⁺/⁶³Cu⁺ isotopic ratio measurements by NF‐LA‐ICP‐MS was 3.9% (n = 9). The detection efficiencies obtained for the compared LA‐ICP‐MS and NF‐LA‐ICP‐MS methods were found to be 4.6 * 10^?3 counts per second (cps)/ablated atom and 2.7 * 10^?5 cps/ablated atom, respectively. Copyright © 2008 John Wiley & Sons, Ltd.     

Investigation of mercury metallothionein complexes in tissues of rat after oral intake of HgCl2

Mercury, a highly toxic metal found widely throughout the environment, is a potent inducer of metallothionein (MT) expression. The role of MTs in the detoxification of mercury after its oral intake in mammals is studied. After feeding rats with mercuric chloride by gastric gavage, the distribution of heavy metals in rat tissues was investigated by inductively coupled plasma mass spectrometry (ICP‐MS). Extensive accumulation of mercury, copper and zinc in kidney and liver is observed. A homemade preparative size‐exclusion chromatography (SEC) column (30 cm × 1.9 cm) packed with Sephadex G‐75 (40–120 µm particle size) gel (Pharmacia) was used for the purification of MT fractions in rat tissues. Preliminary results from SEC indicate that the mercury‐binding MT levels in liver were much lower than in kidney. The MT fractions were collected, desalted, and then separated by reversed‐phase high‐performance liquid chromatography (HPLC) with UV–Vis spectrometry, ICP‐MS and electrospray ionization MS detection. One major and several minor peaks were observed in the HPLC chromatograms of the MT fraction for the kidney sample. UV absorption spectra indicate that MTs were found to bind with mercury. There were no significant mercury‐binding MTs detected in the liver sample using UV detection. ICP‐MS detection showed that mercury‐binding MTs in kidney contained large amounts of mercury and copper but little zinc. Further characterization with ESI‐MS showed that the major peak found in kidney contained Hg₆Cu, Hg₅Cu₂‐MT‐2c and Hg₆‐MT‐2β, Hg₆Cu‐MT‐1γ, Hg₇‐MT‐2α. However, distinction between copper and zinc could not be made based on current mass spectrometric analysis because of instrumental resolution limitations. Copyright © 2005 John Wiley & Sons, Ltd.     

Direct desorption/ionization of analytes by microwave plasma torch for ambient mass spectrometric analysis

Ambient ionization is the new revolution in mass spectrometry (MS). A microwave plasma produced by a microwave plasma torch (MPT) at atmospheric pressure was directly used for ambient mass spectrometric analysis. H₃O⁺ and NH₄⁺ and their water clusters from the background are formed and create protonated molecules and ammoniated molecules of the analytes. In the full‐scan mass spectra, both the quasi‐molecular ions of the analytes and their characteristic ionic fragments are obtained and provide evidence of the analyte. The successful detection of active compounds in both medicine and garlic proves that MPT has the efficient desorption/ionization capability to analyze solid samples. The obtained decay curve of nicotine in exhaled breath indicates that MPT‐MS is a useful tool for monitoring gas samples in real time. These results showed that the MPT, with the advantages of stable plasma, minimal optimization, easy, solvent‐free operation, and no pretreatment, is another potential technique for ambient MS. Copyright © 2013 John Wiley & Sons, Ltd.     

Imaging of metals in biological tissue by laser ablation inductively coupled plasma mass spectrometry (LA–ICP–MS): state of the art and future developments

Laser ablation inductively coupled plasma mass spectrometry (LA–ICP–MS) is well established as a sensitive trace and ultratrace analytical technique with multielement capability for bioimaging of metals and studying metallomics in biological and medical tissue. Metals and metalloproteins play a key role in the metabolism and formation of metal‐containing deposits in the brain but also in the liver. In various diseases, analysis of metals and metalloproteins is essential for understanding the underlying cellular processes. LA–ICP–MS imaging (LA–ICP–MSI) combined with other complementary imaging techniques is a sophisticated tool for investigating the regional and cellular distribution of metals and related metal‐containing biomolecules. On the basis of successful routine techniques for the elemental bioimaging of cryosections by LA–ICP–MSI with a spatial resolution between 200 and ~10 µm, the further development used online laser microdissection ICP–MSI to study the metal distribution in small biological sample sections (at the cellular level from 10 µm to the submicrometer range). The use of mass spectrometric imaging of metals and also nonmetals is demonstrated on a series of biological specimens. This article discusses the state of the art of bioimaging of metals in thin biological tissue sections by LA–ICP–MSI with spatial resolution at the micrometer scale, future developments and prospects for quantitative imaging techniques of metals in the nanometer range. In addition, combining quantitative elemental imaging by LA/laser microdissection–ICP–MSI with biomolecular imaging by matrix‐assisted laser desorption/ionization–MSI will be challenging for future life science research. Copyright © 2013 John Wiley & Sons, Ltd.     

Microwave plasma torch mass spectrometry for some rare earth elements

Rare earth elements (REEs) have been widely applied in modern industry and material science due to their special chemical properties and luminescence properties, but their environment pollution problem has also attracted attention. How to trace and control impact of REEs on environment and develop highly sensitive methods for REEs analysis have practical significance. Microwave plasma torch (MPT) is a kind of simple, low power consumption (～200 W) and easily operated plasma generators. When it was coupled with varied mass spectrometers as ion source of mass spectrometry (MS), i.e. MPT-MS can use for the analysis of metal elements in aqueous with the remarkable advantage of only minimal or even no simple pretreatment, and can meet comprehensive requirements of environmental control and water quality monitoring. MPT-MS have also an ability to carry out online real-time monitoring and analysis of water environment. Compared with the traditional ICP-MS, it can obtain more effective information and has higher sensitivity (the detection limit is at sub-ppb level). This paper reviews common methods and research progress of REEs analysis in recent years. Practical applications and advantages of MPT in the analysis of REEs are briefly summarized. Specifically, this paper introduces some work recently done in our group on analysis of REEs by the MPT, including analysis of metal elements distribution in water samples in local Poyang Lake, and general rules of formation and behavior of complex metal ions in the MPT plasma are also proposed afterwards. Through the practically dealing with the Poyang Lake case by the MPT, hopefully this would interest more academia into this area so as to speed up development of the MPT itself.     

A mass spectrometry‐based method for differentiation of positional isomers of monosubstituted pyrazine N‐oxides using metal ion complexes

A series of 11 pairs of substituted pyrazine N‐oxides, differing in the substituent position, were examined using electrospray ionization mass spectrometry (ESI‐MS) in order to use spectra to assess the differentiation of positional isomers. For each compound, mass spectra were recorded with three different metal cations, namely calcium (II), copper (II) and aluminum (III), with characterization of the observed peaks. Differentiation between regioisomeric N‐oxides has been achieved by comparison of the identity and relative intensities of the peaks originating from the adduct ions formed with the metal ions. Principal component analysis (PCA) has been employed to assist in the interpretation of the results obtained with each metal ion, exploring possible trends according to the nature and position of the substituent in the pyrazine N‐oxide. Copyright © 2015 John Wiley & Sons, Ltd.     

Speciation of Zn‐aminopolycarboxylic complexes by electrospray ionization mass spectrometry and ion chromatography with inductively coupled plasma mass spectrometry

The speciation of Zn‐aminopolycarboxylic complexes was investigated using both electrospray ionization mass spectrometry (ESI‐MS) and ion chromatography (IC) with inductively coupled plasma mass spectrometry (ICP‐MS). The resulting ESI mass spectra indicated that [Zn(HEDTA)]^1?, [Zn(NTA)]^1?, [Zn(EDTA)]^2? and [Zn(DTPA)]^3? were all simultaneously detected in solution; [Zn(NTA)]^1? exhibited the weakest intensity of all these Zn‐aminopolycarboxylic complexes. IC/ICP‐MS was also successfully used to separate Zn complexes by anion‐exchange chromatography using a mobile phase containing 30 mM (NH₄)₂HPO₄ at pH 7.5 giving reasonable resolution within 15 min. A weak peak attributable to the poor stability [Zn(NTA)]^1? ion was also observed using IC/ICP‐MS. With the exception of [Zn(NTA)]^1?, detection limits ranging from 0.5 to 1.0 µg/L were obtained and the proposed method was used for the determination of Zn aminopolycarboxylic complexes in soil solution. Copyright © 2009 John Wiley & Sons, Ltd.     

Electrochemical Analysis of Mercury Using a Kryptofix Carbon‐Paste Electrode

Abstract

Successful applications of different analytical procedures to determine quantitatively mercury in aqueous media can be found in recent literature. Fundamentally it has made use of Cold Vapour Atomic Absorption Spectrometry (CV‐AAS), X‐Ray Fluorescence or UV Spectrophotometry, Inductively Coupled Plasma Atomic Emission Spectrometry (ICP‐AES), or Inductively Coupled Plasma Mass Spectrometry (ICP‐MS), which are the techniques commonly used for trace measurement of heavy metal in the laboratory. In this paper a new and alternative methodology to determine quantitatively mercury in aqueous media is reported. A kryptofix carbon‐paste electrode has been used to determine voltammetrically mercury. The detection limit for mercury was evaluated to be 0.12 µg/l.     

Fourier transform ion cyclotron resonance mass spectral characterization of metal‐humic binding

The interaction between metals and naturally occurring humic substances and the thereby induced issues of bioavailability and hydrogeochemical turnover of metal ions in natural waters have been the subject of intense study for decades. Traditional bulk techniques to investigate metal‐humic binding (e.g. potentiometry and inductively coupled plasma mass spectrometry (ICP‐MS)) can provide quantitative results for the relative abundance and distribution of metal species in humic samples and/or overall binding constants. The shortcoming of these bulk techniques is the absence of structural detail. Ultra‐high‐resolution mass spectrometry, currently the only technique demonstrated to resolve individual humic ions, is not generally employed to provide the missing qualitative information primarily because the identification of metal complexes within the already complex mixtures of humic substances is non‐trivial and time‐consuming to the extent of eliminating any possibility for real‐time manipulation of chelated analytes. Here, it is demonstrated that with tailored selection of the metal ion, it is possible to visually identify large numbers of metal‐humic complexes (～500 for Be²⁺, ～1100 for Mn²⁺, and ～1500 for Cr³⁺) in real‐time as the spectra are being acquired. Metal ions are chosen so that they form primarily even‐m/z complexes with humic ions. These even‐m/z complexes stand out in the spectrum and can readily be characterized based on molecular formulae, which here revealed for example that Suwannee River fulvic acid (SRFA) complexes encompassed primarily highly oxygenated fulvic acids of relatively low double‐bond equivalence. Facile, real‐time identification of even‐m/z metal‐humic complexes additionally allows for the specific selection of metal‐humic complexes for MSⁿ analysis and in‐trap ion‐neutral reactions enabling investigation of metal‐humic complex structure. MS/MS data were collected to demonstrate the potential of the technique as well as highlight some of the remaining challenges. Copyright © 2009 John Wiley & Sons, Ltd.     

The analysis of volatile trace compounds in landfill gases,compost heaps and forest air

Landfill gas, cryotrapped on a loop fashioned from a length of a capillary gas chromatography (GC) column, was examined for volatile organometallic compounds (VOMCs) and for volatile organic compounds (VOCs) by using GC–mass spectrometry (MS). A large number of organic components were present and many were identified, but the only VOMCs present in high enough concentrations to be detected were trimethylstibine and tetramethyltin. The use of inductively coupled plasma (ICP)‐MS as an element‐specific detector allowed the identification of a number of other organometallic species in the landfill gas, including trimethylarsine and trimethylbismuth, and, for the first time, butyltrimethyltin and dibutyldimethyltin. The presence of molybdenum hexacarbonyl was confirmed. Gas from a large‐scale compost heap and from compost incubated in the laboratory contained iodomethane but no common VOMCs (GC–ICP‐MS). Only VOCs were present in forest air (GC–MS). Copyright © 2003 John Wiley & Sons, Ltd.     

Preparation of nanostructured Co–Mo alloy electrodes and investigation of their electrocatalytic activity for hydrazine oxidation in alkaline medium

Cobalt and cobalt–molybdenum alloy electrodes are prepared by galvanic deposition on copper substrates. In this paper, we report a study on the influence of alloying cobalt with molybdenum for the oxidation of hydrazine in 1 M NaOH aqueous solutions. The electrocatalytic properties of the electrodes are studied by cyclic voltammetry (CV), chronoamperometry (CA), and electrochemical impedance spectroscopy (EIS). Scanning electron microscopy (SEM), X‐ray diffraction (XRD), energy‐dispersive X‐ray spectroscopy (EDS,) and inductively coupled plasma (ICP) analysis demonstrate that the structural features and compositions of the as‐prepared Co–Mo coatings vary with the deposition conditions. Electrochemical characterization indicates that the electrochemical properties and the electrocatalytic activity of the investigated alloys were strongly dependent on the microstructural features obtained under different deposition conditions. The overall experimental data indicate that alloying cobalt with molybdenum metal leads to an increase of the electrocatalytic activity in hydrazine electroxidation compared to when using the pure cobalt electrode. High catalytic efficiencies were achieved on Co/25 at.% Mo and Co/33 at.% Mo electrodes, the latter being the best electrocatalyst for hydrazine electroxidation.     

Validation of the determination of copper and zinc in blood plasma and urine by ICP MS with cross-flow and direct injection nebulization

The simultaneous determination of copper and zinc in human plasma and urine by inductively coupled plasma mass spectrometry (ICP MS) is discussed. The performances of a cross-flow nebulizer and a direct-injection nebulizer (DIN) were compared. Flow-injection-DIN-ICP MS analysis of clinical samples using 1-2 mul samples was optimized. Isobaric interferences were discussed and were demonstrated to be eliminated for the (65)Cu and most of the Zn nuclides. The need for standard addition to compensate for signal suppression in the case of some serum samples was indicated. Results obtained by ICP MS using calibration with aqueous standard solutions were found to be in good agreement with those obtained by flame AAS for a batch of real blood plasma and urine samples. The methods developed were validated by analysis of several standard reference materials.     

Polarization induced electrospray ionization mass spectrometry for the analysis of liquid,viscous and solid samples

In this study, a polarization‐induced electrospray ionization mass spectrometry (ESI‐MS) was developed. A micro‐sized sample droplet was deposited on a naturally available dielectric substrate such as a fruit or a stone, and then placed close to (~2 mm) the orifice of a mass spectrometer applied with a high voltage. Taylor cone was observed from the sample droplet, and a spray emitted from the cone apex was generated. The analyte ion signals derived from the droplet were obtained by the mass spectrometer. The ionization process is similar to that in ESI although no direct electric contact was applied on the sample site. The sample droplet polarized by the high electric field provided by the mass spectrometer initiated the ionization process. The dielectric sample loading substrate facilitated further the polarization process, resulting in the formation of Taylor cone. The mass spectral profiles obtained via this approach resembled those obtained using ESI‐MS. Multiply charged ions dominated the mass spectra of peptides and proteins, whereas singly charged ions dominated the mass spectra of small molecules such as amino acids and small organic molecules. In addition to liquid samples, this approach can be used for the analysis of solid and viscous samples. A small droplet containing suitable solvent (5–10 µl) was directly deposited on the surface of the solid (or viscous) sample, placed close the orifice of mass spectrometer applied with a high voltage. Taylor cone derived from the droplet was immediately formed followed by electrospray processes to generate gas‐phase ions for MS analysis. Analyte ions derived from the main ingredients of pharmaceutical tablets and viscous ointment can be extracted into the solvent droplet in situ and observed using a mass spectrometer. Copyright © 2015 John Wiley & Sons, Ltd.     

Quantification issues of trace metals analysis on silicon oxide and nitride films by using VPD‐ICP‐MS and VPD‐GF‐AAS

Vapor phase decomposition (VPD) is a pretreatment technique for collecting trace metal contaminants on the surface of a Si wafer. Such trace metals can be identified and quantified by inductively coupled plasma mass spectrometry (ICP‐MS) or graphite furnace atomic absorption spectroscopy (GF‐AAS). However, the analytical results can be influenced by the Si‐matrix in the VPD samples. This article discusses the approaches to eliminate the interference caused by Si‐matrix. When the thickness of oxide film on wafer surface is less than 100 Å, the quantification results of ICP‐MS analysis will not be affected by Si‐matrix in the VPD samples. Except this, the Si‐matrix must be removed before analysis. An improved heating pretreatment approach has been adopted successfully to eliminate the Si‐matrix. For GF‐AAS analysis, the Si‐matrix will influence the sodium and aluminum analyses. Adding HNO₃ to the graphite furnace tubing after sample injection could also eliminate the interference caused by the Si‐matrix. The method detection limits (MDLs) of VPD‐GF‐AAS and VPD‐ICP‐MS range from 0.04 to 0.55 × 10¹⁰ atoms cm^?2 and 0.05 to 1.73 × 10⁹ atoms cm^?2, respectively. Copyright © 2008 John Wiley & Sons, Ltd.     

微波等离子体炬质谱直接分析水中镉的研究

建立了一种测量水中痕量镉的质谱电离新方法。以微波等离子体炬(MPT)为离子源,结合质谱仪器可直接分析水样而无需任何样品预处理。水样直接通过雾化器雾化形成气溶胶,气溶胶经加热冷却循环及浓硫酸干燥后,由MPT中心管道引入等离子体,产生的离子采用四极杆质谱仪(QMS)检测,得到镉的MPT特征质谱。根据镉的特征质谱进行定量分析。结果表明,114Cd的信号强度与溶液中镉离子浓度在300~3 000ng/L范围内呈良好线性关系,相关系数可达0.994 96,检出限(LOD)为72.7 ng/L。对实际水样(自来水、太湖湖水、赣州龙南井水、矿泉水)进行分析,加标回收率为90.6%~112.2%,10次测量的相对标准偏差(RSD,n=10)为7.1%~21.5%,单个样品测试可在2~3 min内完成。因此,MPT质谱法对水中有害金属镉的快速测量具有一定优势,作为传统ICP质谱检测的有力补充,可以发展成为在线分析方法,应用于环境水、生活水质量监控等领域。     

An analytical method for cyclosporine using liquid chromatography–mass spectrometry

A liquid chromatographic mass spectrometric (LC‐MS) assay has been developed for cyclosporine A (CyA) in rat plasma using amiodarone as internal standard (IS). Rat plasma (100 µL) containing drug and IS were extracted using liquid–liquid extraction with 4 mL of 95:5 ether:methanol. After evaporation of the organic layer the residue was reconstituted with 500 µL of water. Then the aqueous layer was transferred to LC‐MS sample vials. A 10 µL volume was injected. The analysis was performed on a C₈ column 3.5 µm (2.1 × 50 mm) heated to 60°C with a mobile phase consisting of acetonitrile:methanol:0.2% NH₄OH (60:20:20) at an isocratic flow‐rate of 0.2 mL/min. The ions used for quantitation of CyA and IS were m/z 1202.8 and 645.9, with retention times of 3.35 and 4.72 min, respectively. Linear relationships (r² > 0.99) were achieved between plasma or blood concentration and peak height ratios (drug:IS) over the concentration range 50–5000 ng/mL. The CV% and mean error were <19%. Based on validation data, the lower limit of quantification for the assay was 50 ng/mL. The reported assay method displayed high measures of linearity, sensitivity, reliability and precision, allowing its applicability in pharmacokinetic studies in rat. Copyright © 2009 John Wiley & Sons, Ltd.     

Carbon Nanofibers as Solid‐Phase Extraction Adsorbent for the Preconcentration of Trace Rare Earth Elements and Their Determination by Inductively Coupled Plasma Mass Spectrometry

Abstract

Systematic investigations were carried out into the sorption of rare earth elements (REEs) on carbon nonofibers (CNFs) by inductively coupled plasma mass spectrometry (ICP‐MS). The experimental parameters for preconcentration of REEs, such as pH, sample flow rate and volume, eluent concentration, and interfering ions on preconcentration of REEs have been examined in detail. The studied metal ions can be adsorbed quantitatively on CNFs in a pH range from 2.0 to 5.0, and then eluted completely with 0.5 mol l^?1 HNO₃. Based on the above facts, a novel method using a microcolumn packed with carbon nanofibers as an adsorption material was developed for the separation and preconcentration of REEs prior to their determination by ICP‐MS. The proposed method has been successfully applied to the determination of light (La), medium (Eu and Gd) and heavy (Yb) rare earth elements in real sample with the recovery more than 90%. In order to validate this method, two certified reference materials of tea leaves (GBW 07605) and mussel (GBW 08571) were analyzed, and the determined values are in good agreement with the certified values.     

Analysis of diphenylarsinic acid in human and environmental samples by HPLC–ICP‐MS

A simple, rapid and robust analytical method for determining diphenylarsinic acid in human and environmental samples was developed based on a combination of hydrophilic polymer‐based gel‐permeation high‐performance liquid chromatography (HPLC) and inductively coupled plasma mass spectrometry (ICP‐MS). Hair and nail samples were digested with alkali, and liberated diphenylarsinic acid (derivative) was extracted with diethyl ether, redissolved in water and injected for HPLC–ICP‐MS analysis. Human urine, groundwater and water extracts from soils were injected for HPLC–ICP‐MS directly after filtration. Using the method, diphenylarsinic acid in a solution was quantified in 7 min duration for an analysis with a detection limit of sub‐nanograms per milliliter. The method has been applied to groundwater arsenic pollution recently uncovered in Japan. Copyright © 2005 John Wiley & Sons, Ltd.     

Liquid chromatography/tandem mass spectrometry sensitivity enhancement via online sample dilution and trapping: applications in microdosing and dried blood spot (DBS) bioanalysis

A simple online sample dilution, enrichment, and cleanup technique was developed for sensitive microdosing and dried blood spot (DBS) liquid chromatography/tandem mass spectrometric (LC/MS/MS) bioanalysis. Samples are diluted online with water and enriched in a trap column which is subsequently switched inline with the analytical column. Excellent lansoprazole (in acetonitrile) peak shape is maintained even with an 80‐µL injection. In comparison, similar chromatographic peaks were observed only when a small volume of the same solution, i.e., 1 µL, was injected on a regular high‐performance liquid chromatography (HPLC) system, where an injection of 5 µL resulted in severe peak fronting. A substantial enhancement in sensitivity is realized in the trapping mode using large injection volumes. The trap column is washed at the beginning and at the end of each injection with aqueous and organic solvent respectively to remove matrix components. This ultimately leads to reduction of matrix effects and mass spectrometer noise, thus facilitating the utilization of protein precipitation as the sample preparation for plasma samples. A lower limit of quantitation (LLOQ) of 0.5 pg/mL was demonstrated for lansoprazole in human plasma with a signal‐to‐noise (S/N) ratio of 13 using a 100 µL injection. Excellent intra‐day precision and accuracy were established for lansoprazole in human plasma with good linearity (R² > 0.999) from 0.5 to 500 pg/mL. This level of LLOQ makes LC/MS/MS a practical alternative for microdosing bioanalysis, where the dose is typically 100 times lower than the therapeutic dose. The same technique was applied to quantitate lansoprazole in human whole blood employing DBS technology. With a single 3‐mm punch, i.e. ～2 µL of whole blood or ～1 µL plasma, a LLOQ of 0.1 ng/mL showed sufficient S/N ratio (40) for lansoprazole when 75 µL of extract was injected. In all, the online sample dilution, cleanup, and enrichment technique demonstrated the practical utility of LC/MS/MS in microdosing and DBS bioanalysis. Copyright © 2010 John Wiley & Sons, Ltd.     

Continuous flow infrared matrix‐assisted laser desorption electrospray ionization mass spectrometry

Continuous flow infrared matrix‐assisted laser desorption electrospray ionization (CF IR MALDESI) mass spectrometry was demonstrated for the on‐line analysis of liquid samples. Samples in aqueous solution were flowed through a 50 µm i.d. fused‐silica capillary at a flow rate of 1–6 µL/min. As analyte aqueous solution flowed through the capillary, a liquid sample bead formed at the capillary tip. A pulsed infrared optical parametric oscillator (OPO) laser with wavelength of 2.94 µm and a 20 Hz repetition rate was focused onto the capillary tip for sample desorption and ablation. The plume of ejected sample was entrained in an electrospray to form ions by MALDESI. The resulting ions were sampled into an ion trap mass spectrometer for analysis. Using CF IR MALDESI, several chemical and biochemical reactions were monitored on‐line: the chelation of 1,10‐phenanthroline with iron(II), insulin denaturation with 1,4‐dithiothreitol, and tryptic digestion of cytochrome c. Copyright © 2010 John Wiley & Sons, Ltd.