A review of direct liquid introduction interfacing for LC/MS Part I: Instrumental aspects

Summary Considerable progress has been made in the coupling of liquid chromatography and mass spectrometry over the past ten years. Three interfaces tend to dominate the LC/MS market: transport systems, direct liquid introduction, and the thermospray interface. In this paper the developments in direct liquid introduction interfacing for LC/MS will be reviewed. The paper will be published in two parts. Mass spectrometry and applications will be discussed in the second part. This first part of the review concentrates on the various instrumental aspects of direct liquid introduction, such as the design of vacuum systems, the interface probes and the desolvation chambers.     

Liquid chromatography-mass spectrometry coupling and its application in pharmaceutical research

The advantages and technical problems related to the on-line connection of liquid chromatography and mass spectrometry are described, with special emphasis on applications in pharmaceutical chemistry. The most important characteristics of various interfaces, such as direct liquid introduction, Magic, continuous flow fast atom bombardment and thermospray, are discussed. Special applications to the study of thermally very labile compounds are considered.     

Teaching liquid crystals – observation inspired curiosity

Soft matter has become involved in all aspects of everyday life over the past few decades, from diapers and the water-absorbing colloidal crystals hidden in them to the omnipresent liquid crystal displays. This article discusses an introduction to one example of soft matter – liquid crystals – at various educational levels. It stresses the importance of experimental work and presents a few simplified versions of elaborate techniques graduate students later meet in laboratories. A set of simple experiments, which illustrate typical phenomena for liquid crystals, but use different approaches or different materials than liquid crystals, are also presented. Drawing upon analogies is an essential part of an active researcher’s thought processes. By providing analogous experiences and showing clear analogies between various phenomena, a lecturer can train students in the use of analogies as a standard approach when encountering new problems.     

Direct and convenient access to mono 3-hydroxy per-O-methylated α-cyclodextrin

A direct way to reach mono 3-hydroxy per-O-methylated α-cyclodextrin by de-O-methylation with phenylthiotrimethylsilane is reported. This compound is fully characterized by NMR spectroscopy and liquid chromatography with mass spectroscopy coupling.     

Liquid chromatography-inductively coupled plasma mass spectrometry.

The technique of coupling liquid chromatography to inductively plasma mass spectrometry (ICP-MS) is reviewed. A brief introduction to the ICP-MS instrument is given as well as methods to couple the two analytical instruments together. The various types of LC that have been used with ICP-MS detection are discussed and advantages over traditional methods of detection are highlighted, such as the improvements in sensitivity and selectivity. Several applications that have been described in the literature are reviewed. An outlook for the future of LC-ICP-MS, particularly with regard to elemental speciation is given.     

Recent developments in analytical ion trap mass spectrometry

The current status of quadrupole ion trap mass spectrometry is reviewed, with particular emphasis on liquid chromatographic coupling, membrane inlet introduction, laser desorption/ionisation and selective chemical ionisation. The flexibility, high sensitivity and multi-stage tandem mass spectrometric capability of the quadrupole ion trap are all illustrated.     

An overview of LC–MS interfacing systems with selected applications

Advantages and limitations are described for the different LC–MS interfacing systems (moving belt; direct liquid introduction; thermospray; atmospheric pressure ionization with heated pneumatic nebulizer, electrospray, or high flow ion spray; particle beam; and continuous flow fast atom bombardment). Some comments are also made about interfacing capillary zone electrophoresis (CZE). The peculiarities of the various interfaces are described, as are liquid chromatographic requirements prior to mass spectrometry using the different ionization techniques. Selected biological and environmental applications are given.     

On-line electrochemistry--MS and related techniques

This review summarizes publications on the on-line coupling of electrochemistry with mass spectrometry. After a brief historic introduction it is divided into three parts, organized in order of increasing complexity of the experimental arrangement. The first section deals with the use of the electrospray ion source as an electrochemical reactor for oxidation or reduction reactions. It is followed by the second part which covers the hyphenation of different kinds of electrochemical flow cell with a variety of ionization interfaces. The last section focuses on the on-line coupling of chromatographic techniques with electrochemical flow cells and mass spectrometry.     

Analysis of amitrole by normal-phase liquid chromatography and tandem mass spectrometry using a sheath liquid electrospray interface

The coupling of normal-phase liquid chromatography to tandem mass spectrometry, previously developed in our laboratory, has been applied to the analysis of amitrole. This coupling utilizes an electrospray interface modified to accommodate the introduction of a make-up solution at the tip of the electrospray probe. A methanolic solution containing 3 mM ammonium acetate delivered at a flow rate of 10 microL . min(-1) was found to be the optimal sheath liquid to promote successful ionization of the amitrole. Protonated molecules, arising from in-source dissociation of ammonium adducts, were subjected to tandem mass spectrometric experiments in a triple-quadrupole instrument. The main fragmentation reactions were characterized and selected to acquire chromatographic data in the multiple reaction monitoring mode. The limit of detection for amitrole was in the ppm range without any preconcentration step. Enhanced efficiency of ion transmission achievable nowadays in mass spectrometers (this analytical configuration was developed with a 15-year-old instrument) is reasonably expected to further improve this detection level.     

有机试液的电感耦合等离子体原子发射光谱分析 Ⅰ.实际应用的若干方面

本文从七个方面介绍了ICP-AES在有机试液直接分析中的应用:(1) 油类样品分析;(2) 酒样直接分析;(3) 溶剂萃取分离富集-ICP光谱分析;(4) 基于生成挥发性金属有机化合物的ICP进样方法;(5) 有机试液分析中的其它进样方法;(6) 有机介质中非金属元素的ICP-AES测定;(7) ICP-AES作为色谱法的检测器。     

Microfabricated liquid junction hybrid capillary electrophoresis‐mass spectrometry interface for fully automated operation

One of the challenging instrumental aspects in coupling an automated CE instrument with ESI mass spectrometry (CE‐MS) is finding the balance between the stability, reproducibility and sensitivity of the analysis and compatibility with the standard CE instrumentation. Here, we present a development of a new liquid junction based electrospray interface for automated CE‐MS, with a focus on the technical design followed by computer modeling of transport conditions as well as characterization of basic performance of the interface. This hybrid arrangement designed as a microfabricated unit attachable to the automated CE instrument allows using of a wide range of separation capillaries with respect to their diameter, length or internal coating (e.g., for suppressed electroosmotic flow). Different compositions of the ESI liquid and background electrolyte solutions can be used if needed. The microfabricated part, prepared by laser machining from polyimide, includes a self‐aligning liquid junction, a short transport channel, and a pointed sprayer for the electrospray ionization. This microfabricated part is positioned in a plastic connection block securing the separation capillary and flushing ports. Transport conditions were modelled using computer simulation and the real life performance of the interface was compared to that of a commercial sheath liquid interface. The basic performance of the interface was demonstrated by separations of peptides, proteins, and oligosaccharides.     

Comparison of mass spectrometric methods for studying thermally labile compounds: Rifapentine

Results of 16 different mass spectrometric ionization and sample-introduction methods are compared for the case of a thermally very labile antibiotic, rifapentine. These suggest that extensive thermal decomposition occurs during evaporation when the sample can come into contact with hot metal parts, usually the source housing. The intensity of the molecular ion and the extent of fragmentation depend on various parameters, such as the ionization process, positive or negative-ion detection and the type of sample introduction. The most informative methods for rifapentine seem to be ‘in-beam’ electron impact, negative ionization with particle beam and direct liquid introduction interfaces and positive- and negative-ion fast atom bombardment.     

Changing need for bioanalysis during drug development

Recent years have witnessed the introduction of several high-quality review articles into the literature covering various scientific and technical aspects of bioanalysis, including chirality aspects. Now it is widely accepted that bioanalysis is an integral part of the pharmacokinetic/pharmacodynamic characterization of a novel chemical entity (NCE) from the time of its discovery and during various stages of drug development leading to its market authorization. There is a need for a comprehensive review article that takes into account the changing faces of bioanalysis from the time of inception of an NCE at the discovery stage and as the NCE moves forward in development. This review attempts to cover the versatility in the applicability of bioanalytical aspects with respect to the nature, rigor and available choices of analyses. For ease of understanding, bioanalytical aspects are discussed under sections covering discovery, preclinical and clinical stages. It is intended to give some general thoughts in this area which will form basis of a general framework as to how one would approach bioanalysis from inception (i.e. discovery of a lead molecule) and progressing through various stages of drug development.     

Reduction of a quaternary phenanthridinium salt in a chemical ionization source when introduced by direct injection in acetonitrile

Reduction of phenanthridinium methiodide to its dihydroderivative was observed when a solution of the sample in acetonitrile was injected in the chemical ionization source of a combined liquid chromatograph/mass spectrometer equipped with a direct liquid introduction interface and a polarized desolvation chamber.     

Quantification of small molecules in plasma with direct analysis in real time tandem mass spectrometry, without sample preparation and liquid chromatographic separation

Recently, a new ion source, Direct Analysis in Real Time (DART), has been introduced which allows direct biological sample introduction into a mass spectrometry (MS) system. The elimination of conventionally required sample preparation and separation by high-performance liquid chromatography (HPLC) prior to MS analysis represents a remarkable opportunity to reduce assay turn-around time, environmental impact and capital/manpower investment. This new technology initially was used in various qualitative applications to directly detect chemicals on solid surfaces, in liquids and gases. In this study, a DART source operating under ambient pressure with ground potential was installed onto a Sciex 4000 tandem mass spectrometer and employed in the sample analysis of plasma based on direct introduction into the DART-MS/MS system. Reasonable precision and accuracy (%CV and %Error, both <10%) were achieved of a significant number of compounds tested in biological fluids. In addition, the limit of detection for 80% of the tested compounds reached 5 ng/mL or lower which is sufficient for pharmaceutical drug discovery support. Finally, experimental conditions that significantly impacted assay performance were investigated with respect to optimization and limitation. Because of its simplicity, fast data acquisition (3-5 s) and low cost, DART has the potential to significantly impact quantitative pharmaceutical analysis in biological matrices.     

Liquid chromatography-mass spectrometry of trace compounds with a moving-belt interface and multi-dimensional chromatography

A high-performance liquid chromatographic method with on-line mass spectrometric detection is described for the structural analysis of a number of synthetic impurities, present at trace levels in almitrine. To obtain mass spectra with various ionization methods and high-resolution mass measurements, a moving-belt liquid chromatograph-mass spectrometer interface is used. A two-column switching system allows the injection of large amounts of almitrine, from which the trace compounds are trapped on a second column, while discarding the major component. This permits the introduction of the impurities into the mass spectrometer by elution of the second column, without the risk of introducing too large an amount of the major compound into the mass spectrometer. The mass spectra thus obtained are of sufficient quality to permit a correct structural assignment of the impurities.     

Microporous hollow fibers for gas absorption : I. Mass transfer in the liquid

Microporous hollow fiber modules offer a larger area per volume between gas and liquid than that commonly encountered in packed towers. This larger area can be sustained at very low flows, where packed towers will not be loaded, and at very high flows, where packed towers will flood. As a result, the modules offer the potential of faster mass transfer. This potential can be compromised by the resistance to mass transfer of the membrane itself, a resistance which is increased if the liquid wets the membrane. The results presented in this two-part series show when the advantage of the increased area is greater than the disadvantage of the membrane resistance. In this part, a theory for the operation of hollow fiber membrane modules is developed, and mass transfer coefficients in the liquid phase are investigated.     

Coupling of nanoflow liquid chromatography to matrix-assisted laser desorption/ionization mass spectrometry: real-time liquid chromatography run mapping on a MALDI plate

The major obstacle in the use of matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) instruments in the analysis of complex proteome samples is the lack of a direct coupling of a highly resolving separation technique with the mass spectrometer itself. To overcome this drawback, a spotting device for capillary and nanoflow liquid chromatography (LC) with a special liquid deposition principle for lowest volumes was developed. The instrument is able to perform MALDI spotting in real time in order to deposit the LC run on the MALDI plate, and therefore couples the high resolution power of nano-RP-HPLC separation directly with MALDI-MS. This work describes the development and optimization of a method for spotting with online matrix addition, and illustrates its use in the analysis of a complex proteome sample.     

A Microcomputer Controlled Tandem Quadrupole Mass Spectrometer Using a Direct Liquid Introduction Probe for Screening Analysis

Abstract

The use of a direct liquid introduction probe with a short guard column as the method of sample introduction is explored. This technique is an alternative to the conventional direct probe method. The method is rapid, involatile compounds can be analyzed, and volatile compounds are not lost in the vacuum lock. Screening for trichlorophenol in urine, by observing the loss of [M-HCOCI]⁺, is used to test the technique. The advantages and disadvantages of split and splitless direct liquid introduction probes and column concentration are discussed. Detection limits in the low nanograms were observed, and samples may be analyzed every 30 seconds.     

Microporous hollow fibers for gas absorption : II. Mass transfer across the membrane

Microporous hollow fiber modules offer a larger area per volume between gas and liquid than that commonly encountered in packed towers. This larger area can be sustained at very low flows, where packed towers will not be loaded, and at very high flows, where packed towers will flood. As a result, the modules offer the potential of faster mass transfer. This potential can be compromised by the resistance to mass transfer of the membrane itself, a resistance which is increased if the liquid wets the membrane. The results presented in this two-part series show when the advantage of the increased area is greater than the disadvantage of the membrane resistance. In this part, overall mass transfer coefficients are studied, including resistances in both liquid and membrane, and the performance of hollow fibers is compared with that of packed towers.