Evaluation of gel electrophoresis conditions for the separation of metal‐tagged proteins with subsequent laser ablation ICP‐MS detection

Although laser ablation (LA)‐ICP‐MS has been reported for the determination of metalloproteins separated by gel electrophoretic techniques (GE), systematic studies that define the conditions essential for successful measurements are still scarce. In this paper we present the results of our studies of basic conditions for the effective application of GE‐LA‐ICP‐MS for the separation of metal‐binding proteins, focusing on their stability during GE and post‐separation gel treatment. The stability of metal–protein complexes (haemoglobin, myoglobin, superoxide dismutase, carbonic anhydrase, transferrin, albumin, cytochrome c) during GE is dependent on the nature of the metal–protein interaction and the principle of separation. We have observed that non‐denaturing GE is a suitable separation technique for most metal–protein complexes (e.g. Zn in carbonic anhydrase and Fe in Tf and myoglobin were quantitatively recovered in a spiked liver cytosol), whereas separation by denaturing GE strongly impaired the stability of the complexes. Equally important is the post‐separation treatment of the gel to enable successful detection of the metal. LA‐ICP‐MS requires drying of the gel without loss of protein‐bound metal or cracking of the gel. This was successfully achieved using glycerol followed by heating. We demonstrate that staining of the gel prior to LA‐ICP‐MS using silver or Coomassie blue is not recommended, since most protein‐bound metal is lost during the staining procedure. Furthermore it has been shown that only line scanning with a speed of less than 30 μm/s can reliably distinguish between lines 1 mm apart, while raster spot analysis carries the risk of misinterpretation due to contamination in/on inhomogeneous gels.     

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.     

Speciation Analysis of Thallium by Reversed‐phase Liquid Chromatography ‐ Inductively Coupled Plasma Mass Spectrometry

An inductively coupled plasma mass spectrometer (ICP‐MS) was used as a liquid chromatographic detector for the speciation analysis of thallium in environmental samples. In this study, ionic thallium species, namely Tl(I) and Tl(III) were well separated by reversed‐phase high performance liquid chromatography (RP‐HPLC) with a C8‐HPLC column as the stationary phase and 1 mmol L^?1 tetrabutylammonium phosphate (TBAP), 2 mmol L^?1 diethylenetriamine pentaacetic acid (DTPA) in 1% v/v methanol solution (pH 6) as the mobile phase. Effluent from the HPLC column was delivered to the nebulizer of the ICP‐MS for the determination of thallium. The separation was complete in less than 3 min. Detection limit was 0.002 μg L^?1 for both Tl(I) and Tl(III) compounds based on peak height. The relative standard deviation of the peak areas for five injections of a mixture containing 1 μg Tl L^?1 was better than 3.4%. The concentrations of Tl compounds were determined in standard reference materials, including NIST SRM 1643e Trace Elements in Water and NRCC NASS‐5 Open Ocean Seawater and water samples collected in Kaohsiung area, Taiwan. The HPLC‐ICP‐MS results of the reference samples agreed with the reference values. This method has also been applied to determine Tl(I) and Tl(III) compounds in custard apple (Annona squamosa) leaves collected from Chai‐shan Mountain, Kaohsiung and Taitung City, Taiwan. The thallium species were quantitatively leached from the leaves with a 5 mmol L^?1 DTPA in 100 mmol L^?1 ammonium acetate solution in an ultrasonic bath during a period of 30 min. The HPLC‐ICP‐MS result that was obtained after the analysis of leaves sample showed a satisfactory agreement with the total thallium concentration obtained by ICP‐MS analysis of completely dissolved sample.     

CE with on‐line detection by ICP‐MS for studying the competitive binding of zinc against cadmium for glutathione

Development of a feasible method for studying the competitive interaction between a pair of antagonists is essential for understanding the antagonism of trace metals in biological systems. Herein, we report the application of CE on‐line coupled with ICP mass spectroscopy (CE‐ICP‐MS) to investigate the competitive binding of Zn²⁺ against Cd²⁺ for glutathione (GSH), which is related to the detoxification of Cd²⁺ in biological system, and introduce a method to evaluate the kinetics and thermodynamics for the competitive binding of Zn²⁺ against Cd²⁺ for GSH. The CE‐ICP‐MS hybrid technique allows easy and sensitive probing of the competitive binding of Zn²⁺ against Cd²⁺ for GSH and quantitative determination of the important thermodynamic and kinetic parameters of the competitive binding of Zn²⁺ against Cd²⁺ for GSH. Owing to the high sensitivity and element selectivity with multi‐elements detection capacity of ICP‐MS, we detailed the evaluation of the kinetics and thermodynamics describing the competition of Zn²⁺ against Cd²⁺ for GSH from the systematic data obtained by CE‐ICP‐MS. The competitive binding of Zn²⁺ against Cd²⁺ for GSH was demonstrated exothermic and thermodynamically favorable (ΔG=?7.2 kJ/mol) and driven entirely by a large favorable enthalpy decrease (ΔH=?15.1 kJ/mol) but with an unfavorable entropy decrease (ΔS=?25.6 J/mol/K). The kinetic data were fit to a second‐order equation with the reaction rate constant (k) of (2.18±0.10)×10² L/(mol·s) under the simulated physiological condition.     

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.     

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.     

MeCAT peptide labeling for the absolute quantification of proteins by 2D‐LC‐ICP‐MS

Metal‐Coded Affinity Tags (MeCAT) reagents were devised for the absolute quantification of labeled proteins and peptides using inductively coupled plasma mass spectrometry (ICP‐MS). After the recent publication of quantification approaches for digested proteins, this work presents a multidimensional strategy for the application of MeCAT to samples which require higher chromatographic resolution. Two‐dimensional separations based on strong cation exchange (SCX) and reversed‐phase (RP) chromatography, were used for the quantification of lysozyme, bovine serum albumin and transferrin after tryptic digestion. The elution protocols were optimized to improve the resolution of the MeCAT‐labeled peptides which led to faster elutions in SCX and longer retention times in RP compared with unlabeled peptides. The optimized method provided enough resolution for the samples analyzed. Peptides losses during the whole procedure were studied. Although recoveries of greater than 90% were found in the RP dimension, important global losses in the two‐dimensional offline approach forced us to use specific internal standards, in this case MeCAT‐labeled standard peptides. External calibration and label‐specific isotope dilution analysis (IDA) were tested and compared as possible quantification techniques. While both techniques showed accurate and precise determinations, the label‐specific IDA technique resulted in more straightforward measurements and more affordable external calibrations. Finally, simultaneous quantification of three different samples labeled with different lanthanides was successfully performed demonstrating the potential of MeCAT combined with ICP‐MS for multiplexing. Electrospray ionization mass spectrometry techniques provided the structural information needed for the identification of the labeled species. Copyright © 2012 John Wiley & Sons, Ltd.     

Study on capillaries covalently bound with phospholipid vesicles for open‐tubular CEC and application to on‐line open‐tubular CEC‐MS

Phospholipid vesicles were covalently attached to iminoaldehyde‐coated fused silica capillaries and applied to the separation of model steroids by open‐tubular CEC (OT‐CEC). The effects of reducing the formed Schiff's base with sodium borohydride and of the liposome composition on the stability of the coating were investigated. In addition, the studies were focused on the optimization of running conditions (pH values and composition of BGE solution) when CEC, using capillaries covalently bound with liposome dispersions, was coupled to MS. The effect of cholesterol in the liposome dispersion on the binding of model analytes was studied, using liposome dispersions comprising 80:20 mol% zwitterionic 1‐palmitoyl‐2‐oleyl‐sn‐glycero‐3‐phosphocholine (POPC) and the negatively charged phospholipid 1 ‐ palmitoyl‐2‐oleoyl‐sn‐glycero‐3‐phospho‐l ‐serine (POPS) and 40:40:20 mol% POPC/POPS/cholesterol. Cholesterol in liposomes (greatly) enhanced the stability of the capillaries by making the coatings more rigid, resulting in lower retention factors for all the studied model steroids. Although most of the studies were carried out by open tubular CEC‐UV Vis, the applicability of the capillaries to on‐line CEC‐MS was demonstrated as well. On‐line CEC‐MS studies on model steroids proved the suitability of coated capillaries for analyte–lipid membrane interaction studies, and especially for such analytes that are difficult to detect by conventional on‐line UV Vis.     

Dual‐column capillary microextraction (CME) combined with electrothermal vaporization inductively coupled plasma mass spectrometry (ETV‐ICP‐MS) for the speciation of arsenic in human hair extracts

In this work, dual‐column capillary microextraction (CME) system consisting of N‐(2‐aminoethyl)‐3‐aminopropyltrimethoxysilane (AAPTS)‐silica coated capillary (C1) and 3‐mercaptopropyl trimethoxysilane (MPTS)‐silica coated capillary (C2) was developed for sequential separation/preconcentration of arsenite [As(III)], arsenate [As(V)], monomethylarsonic acid [MMA(V)] and dimethylarsinic acid [DMA(V)] in the extracts of human hair followed by electrothermal vaporization inductively coupled plasma mass spectrometry (ETV‐ICP‐MS) detection with iridium as permanent modifier. Various experimental parameters affecting the dual‐column microextraction of different As species had been investigated in detail. It was found that at pH 9, As(V) and MMA could be quantitatively retained by C1 and only As(III) could be quantitatively retained by C2. With the aid of valve switching, As(V)/MMA(V) retained on C1 and As(III) retained on C2 could be sequentially desorbed by 10 µl of 0.01 mol l^?1 HNO₃ [for As(V)], 0.1 mol l^?1 HNO₃ [for MMA(V)] and 0.2 mol l^?1 HNO₃‐3% thiourea (m/v) [for As(III)], respectively, the eluents were immediately introduced into the Ir‐coated graphite tubes for further ETV‐ICP‐MS detection. With two‐step ETV pyrolysis program, Cl^? in the sample matrix could be in situ removed, and the total As in the human hair extracts or digested solution could be interference‐free, determined by ETV‐ICP‐MS. DMA(V) in the human hair extracts was obtained by subtraction of total As in the human hair extracts from other three As species. Under the optimized conditions, the detection limits (3 σ) of the method were 3.9 pg ml^?1 for As(III), 2.7 pg ml^?1 for As(V), 2.6 pg ml^?1 for MMA(V) and 124 pg ml^?1 for total As with the relative standard deviations less than 7.0% (C = 0.1 ng ml^?1, n = 7), and the enrichment factor was 286, 262 and 260 for As(III), As(V) and MMA(V), respectively. The developed method was successfully applied for the speciation of arsenic in the extracts of human hair. Copyright © 2009 John Wiley & Sons, Ltd.     

HPLC‐PAD‐atmospheric pressure chemical ionization‐MS metabolite profiling of cytotoxic carotenoids from the echinoderm Marthasterias glacialis (spiny sea‐star)

An HPLC‐PAD‐atmospheric pressure chemical ionization‐MS metabolite profiling analysis was conducted on the marine echinoderm Marthasterias glacialis (spiny sea‐star). Bio‐guided purification of the methanolic extract led to the isolation of several carotenoids, namely zeaxanthin, astaxanthin and lutein. These compounds were characterized using both UV–Vis characteristics and MS spectra interpretation. No previous works addressed the MS analysis of carotenoids present in this organism. The purified carotenoid fraction displayed a strong cell proliferation inhibition against rat basophilic leukemia RBL‐2H3 (IC₂₅=268 μg/mL) cancer cell line. Against healthy V79 (rat lung fibroblasts (IC₂₅=411 μg/mL)) cell line, however, toxicity was lower, as it is desired for anti‐cancer molecules. This study suggests that M. glacialis may constitute a good source of bioactive compounds that can be used as lead compounds for the pharmaceutical industry.     

Characterization and screening of metals,metalloids and biomarkers in crude oil by ICP–MS/OES,and GC–MS techniques after digestion by microwave‐induced combustion

A method for digestion of light and medium Iraqi crude oils (Basrah and Khanaken oils) using microwave‐induced combustion (MIC) in closed vessels is described for the determination of Hg, Au, Cu, Al, Ca, Co, K, Mg, Si and Sr by inductively coupled plasma optical emission spectrometry (ICP–OES) and Mo, Ti, Mn, Li, Se^?1, Rb, Ag, Ba, Pb, As, Cd, Cr, Fe, Ni, V and Zn by inductively coupled plasma mass spectrometry (ICP–MS). Upon using MIC it was possible to obtain lower limits of detection by ICP–MS and also by ICP–OES compared with those obtained by microwave‐assisted digestion. The MIC was the best choice with regard to the possibility of using dilute nitric acid as an absorbing solution, which is important to minimize the interference encountered by ICP–MS and ICP–OES.The physicochemical parameters and some contaminants of crude oil samples were analyzed to classify and assess the quality of the crude oils. This study determines the viability of the use of Fourier transform infrared spectroscopy as an alternativee to traditional petroleum geochemical methods for crude oil characterization. The infrared fingerprints agree with the results obtained from GC–MS analysis.     

Phase‐Separable Polyisobutylene Palladium‐PEPPSI Precatalysts: Synthesis and Application in Buchwald–Hartwig Amination

This paper reports the efficient synthesis of the first class of polyisobutylene(PIB)‐supported palladium‐PEPPSI precatalyst (PEPPSI = pyridine‐enhanced precatalyst preparation, stabilization, and initiation). The new complexes are employed in Buchwald–Hartwig amination of aryl chlorides and are found to be reasonably active in the titled cross‐coupling reaction. The supported catalysts are tested in polar (1,4‐dioxane and 1,2‐dimethoxyethane) as well as in aliphatic reaction media (toluene and n‐heptane) and display superior activity in the highly lipophilic solvent (n‐heptane). The catalytic efficacy of PIB‐Pd‐PEPPSI precatalyst is measured to be comparable to its nonsupported analog. Pd‐leaching is determined by inductively coupled plasma mass spectrometry (ICP‐MS) after a simple liquid/liquid extraction and is found to be 2 ppb in the product phase, translating into a recovery of ≈99.8% of the palladium.     

Protective encapsulation of acid‐sensitive catalysts using polyethylene ligands

The stability of polyethylene oligomer (PE_Olig)‐entrapped salen‐metal complexes toward acidolysis is described. These complexes dissolve in hot toluene and precipitate as hydrophobic powders. The salen species in these precipitates or in precipitates of admixtures of oligomeric complexes and unfunctionalized polyethylene are stable to acid when suspended in acidic methanol for 24 h at 25°C. The lack of metal leaching due to acid‐promoted demetalation was determined using both colorimetric and ICP‐MS analyses. The ICP‐MS results showed the amount of metal loss for PE_Olig‐salen‐metal complexes was 0.27%, 0.45%, and 0.79% for half‐salen Cr(III), salen Cr(III), and salen Mn(III) complexes, respectively. These results were in contrast to the reported behavior of low molecular weight salen metal complexes and to results seen with a salen complex bound to divinylbenzene (DVB) crosslinked polystyrene which demetalates under acidic conditions at room temperature. Salen complexes formed with PE_Olig complexes also demetalate when the PE_Olig‐bound species are in solution at elevated temperature and exposed to acid. These results show that as solids oligomeric polyethylene ligands even without added PE can serve as a protective encapsulating matrix for the solid forms of polymer‐supported catalysts. © 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2012     

Modern MALDI time‐of‐flight mass spectrometry

This paper focuses on development of time‐of‐flight (TOF) mass spectrometry in response to the invention of matrix‐assisted laser desorption/ionization (MALDI). Before this breakthrough ionization technique for nonvolatile molecules, TOF was generally considered as a useful tool for exotic studies of ion properties but was not widely applied to analytical problems. Improved TOF instruments and software that allow the full potential power of MALDI to be applied to difficult biological applications are described. A theoretical approach to the design and optimization of MALDI‐TOF instruments for particular applications is presented. Experimental data are provided that are in excellent agreement with theoretical predictions of resolving power and mass accuracy. Data on sensitivity and dynamic range using kilohertz laser rates are also summarized. These results indicate that combinations of high‐performance MALDI‐TOF and TOF‐TOF with off‐line high‐capacity separations may ultimately provide throughput and dynamic range several orders of magnitude greater than those currently available with electrospray LC‐MS and MS‐MS. Copyright © 2009 John Wiley & Sons, Ltd.     

The human mast cell line‐1 cell membrane chromatography coupled with HPLC‐ESI‐MS/MS method for screening potentical anaphylactic components from chuanxinlian injection

Chuanxinlian injection is a traditional Chinese medicine injection widely used in China to treat sore throat, cough and dysentery, although a high occurrence of severe adverse reactions has been reported in clinical practice in recent years. In the present study, a human mast cell line‐1 cell membrane chromatography coupled with HPLC‐ESI‐MS/MS method was established to screen and identify potentical anaphylactic components in chuanxinlian injection, and the dehydroandrographolide was identified as a potential anaphylactic component. In vitro anaphylactic assay showed that intracellular Ca²⁺ concentration clearly increased under dehydroandrographolide (100 μm ) treatment. β ‐Hexosaminidase and histamine release in human mast cell line‐1 cells were both markedly enhanced with increased concentrations of dehydroandrographolide, confirming the anaphylactic activity of dehydroandrographolide. The application for chuanxinlian injection in this study suggested that the developed human mast cell line‐1 cell membrane chromatography coupled with HPLC‐ESI‐MS/MS system may be effective and rapid for screening the potentical anaphylactic components from complex samples.     

Determination of UV filters in river water samples by in‐line SPE‐CE‐MS

The use of SPE coupled in‐line to CE using electrospray MS detection (in‐line SPE‐CE‐ESI‐MS) was investigated for the preconcentration and separation of four UV filters: benzophenone‐3, 2,2‐dihydroxy‐4‐methoxybenzophenone, 2,4‐dihydroxybenzophenone and 2‐phenylbenzimidazole‐5‐sulphonic acid. First, a CE‐ESI‐MS method was developed and validated using standard samples, obtaining LODs between 0.06 μg/mL and 0.40 μg/mL. For the in‐line SPE‐CE‐ESI‐MS method, three different sorbents were evaluated and compared: Oasis HLB, Oasis MCX, and Oasis MAX. For each sorbent, the main parameters affecting the preconcentration performance, such as sample pH, volume, and composition of the elution plug, and sample injection time were studied. The Oasis MCX sorbent showed the best performance and was used to validate the in‐line SPE‐CE‐ESI‐MS methodology. The LODs reached for standard samples were in the range between 0.01 and 0.05 ng/mL with good reproducibility and the developed strategy provided sensitivity enhancement factors between 3400‐fold and 34 000‐fold. The applicability of the developed methodology was demonstrated by the analysis of UV filters in river water samples.     

Conductivity as a Sensor for Monitoring Relative Magnesium Corrosion Rates in Real‐time,in Serum‐containing Media under Cell Culture Conditions

Because controlling the corrosion rate of magnesium metal will be crucial to the success of biomedical implants containing pure magnesium or magnesium alloys, many ways have been sought to improve in vitro tests to analyze corrosion rates, and also to identify new methods of preparing or post‐processing magnesium. In this work, for an in vitro assay, we explored the use of a commercially available conductivity sensor to study magnesium corrosion under cell culture conditions that duplicate many physiologically appropriate parameters. With this sensor, we studied the corrosion of two previously untested magnesium single crystal samples that differed in surface treatments that could alter corrosion rates. The results show that the relative conductivity changes in (mS/cm) over the total time of immersion were proportional to the corrosion rates in (mm/y) and also to the total magnesium released, as detected by inductively coupled plasma mass spectrometry (ICP‐MS).     

Surface‐Directed Spinodal Decomposition of Solvent‐Quenched Organic Transistor Blends

This paper describes the first example of the application of a combination of the Flory–Huggins and Cahn–Hilliard theories to model and simulate microstructure evolution in solution‐processed functional blend layers of organic semiconductors, as used in organic electronics devices. Specifically, the work considers phase separation of the active blend components of organic transistors based on triisopropylsilylpentacene (TIPS‐pentacene) and poly(α‐methylstyrene) (PαMS). By calculation and estimation of relevant physical parameters, it is shown that the vertically phase‐separated structure observed in as‐cast blend layers containing PαMS of a sufficiently high molecular weight (of the order of 10² kDa) evolves via surface‐directed spinodal decomposition. The surface‐directed effect can already be triggered by small differences in substrate– and/or air–interface interaction energies of the separating phases. During phase separation, which commences at the interfaces, bulk features of the TIPS‐enriched phase formed by thermal noise collapse to give the experimentally observed trilayer structure of TIPS–PαMS–TIPS. The reported near absence of solution‐state phase separation of as‐cast blend layers containing a low molecular weight PαMS (of the order of 1 kDa) is also reproduced.     

Recent advances in capillary electrophoresis‐mass spectrometry: Instrumentation,methodology and applications

Capillary electrophoresis (CE) offers fast and high‐resolution separation of charged analytes from small injection volumes. Coupled to mass spectrometry (MS), it represents a powerful analytical technique providing (exact) mass information and enables molecular characterization based on fragmentation. Although hyphenation of CE and MS is not straightforward, much emphasis has been placed on enabling efficient ionization and user‐friendly coupling. Though several interfaces are now commercially available, research on more efficient and robust interfacing with nano‐electrospray ionization (ESI), matrix‐assisted laser desorption/ionization (MALDI) and inductively coupled plasma mass spectrometry (ICP) continues with considerable results. At the same time, CE‐MS has been used in many fields, predominantly for the analysis of proteins, peptides and metabolites. This review belongs to a series of regularly published articles, summarizing 248 articles covering the time between June 2016 and May 2018. Latest developments on hyphenation of CE with MS as well as instrumental developments such as two‐dimensional separation systems with MS detection are mentioned. Furthermore, applications of various CE‐modes including capillary zone electrophoresis (CZE), nonaqueous capillary electrophoresis (NACE), capillary gel electrophoresis (CGE) and capillary isoelectric focusing (CIEF) coupled to MS in biological, pharmaceutical and environmental research are summarized.