The potential of inductively coupled plasma mass spectrometry detection for high-performance liquid chromatography combined with accurate mass measurement of organic pharmaceutical compounds

Quantification of unknown components in pharmaceutical, metabolic and environmental samples is an important but difficult task. Most commonly used detectors (like UV, RI or MS) require standards of each analyte for accurate quantification. Even if the chemical structure or elemental composition is known, the response from these detectors is difficult to predict with any accuracy. In inductively coupled plasma mass spectrometry (ICP-MS) compounds are atomised and ionised irrespective of the chemical structure(s) incorporating the element of interest. Liquid chromatography coupled with inductively coupled plasma mass spectrometry (LC/ICP-MS) has been shown to provide a generic detection for structurally non-correlated compounds with common elements like phosphorus and iodine. Detection of selected elements gives a better quantification of tested 'unknowns' than UV and organic mass spectrometric detection. It was shown that the ultrasonic nebuliser did not introduce any measurable dead volume and preserves the separation efficiency of the system. ICP-MS can be used in combination with many different mobile phases ranging from 0-100% organic modifier. The dynamic range was found to exceed 2.5 orders of magnitude. The application of LC/ICP-MS to pharmaceutical drugs and formulations has shown that impurities can be quantified below the 0.1 mol-% level.     

电感耦合等离子体质谱(ICP-MS)及其联用技术在核工业领域的应用进展

综述了电感耦合等离子体质谱(ICP-MS)及其联用分析技术的进展,论述了其在相关核工业及环境领域中分析痕量或超痕量的放射性同位素、长寿命核素、元素形态等的应用。讨论了电感耦合等离子体质谱及联用技术的发展趋势,并对目前存在的主要问题及可能的解决方案进行了讨论。     

Inorganic trace analysis by mass spectrometry

Mass spectrometric methods for the trace analysis of inorganic materials with their ability to provide a very sensitive multielemental analysis have been established for the determination of trace and ultratrace elements in high-purity materials (metals, semiconductors and insulators), in different technical samples (e.g. alloys, pure chemicals, ceramics, thin films, ion-implanted semiconductors), in environmental samples (waters, soils, biological and medical materials) and geological samples. Whereas such techniques as spark source mass spectrometry (SSMS), laser ionization mass spectrometry (LIMS), laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS), glow discharge mass spectrometry (GDMS), secondary ion mass spectrometry (SIMS) and inductively coupled plasma mass spectrometry (ICP-MS) have multielemental capability, other methods such as thermal ionization mass spectrometry (TIMS), accelerator mass spectrometry (AMS) and resonance ionization mass spectrometry (RIMS) have been used for sensitive mono- or oligoelemental ultratrace analysis (and precise determination of isotopic ratios) in solid samples. The limits of detection for chemical elements using these mass spectrometric techniques are in the low ng g⁻¹ concentration range. The quantification of the analytical results of mass spectrometric methods is sometimes difficult due to a lack of matrix-fitted multielement standard reference materials (SRMs) for many solid samples. Therefore, owing to the simple quantification procedure of the aqueous solution, inductively coupled plasma mass spectrometry (ICP-MS) is being increasingly used for the characterization of solid samples after sample dissolution. ICP-MS is often combined with special sample introduction equipment (e.g. flow injection, hydride generation, high performance liquid chromatography (HPLC) or electrothermal vaporization) or an off-line matrix separation and enrichment of trace impurities (especially for characterization of high-purity materials and environmental samples) is used in order to improve the detection limits of trace elements. Furthermore, the determination of chemical elements in the trace and ultratrace concentration range is often difficult and can be disturbed through mass interferences of analyte ions by molecular ions at the same nominal mass. By applying double-focusing sector field mass spectrometry at the required mass resolution—by the mass spectrometric separation of molecular ions from the analyte ions—it is often possible to overcome these interference problems. Commercial instrumental equipment, the capability (detection limits, accuracy, precision) and the analytical application fields of mass spectrometric methods for the determination of trace and ultratrace elements and for surface analysis are discussed.     

Capillary electrophoresis coupled to inductively coupled plasma mass spectrometry (CE/ICP-MS) and to electrospray ionization mass spectrometry (CE/ESI-MS): An approach for maximum species information in speciation of selenium

On-line hyphenations consisting of a separation and a detection step are one of the most efficient techniques for identification and characterization of metal containing species. The high resolution power of capillary electrophoresis (CE) is used for the separation of three selenium species, whereas either electrospray ionization mass spectrometry (ESI-MS) or inductively coupled plasma mass spectrometry (ICP-MS) are taken for molecule or element specific detection. This work gives an overview about the possibilities and limitations, when using the two hyphenated systems for speciation investigations. In order to show the power of the two complementary techniques, a CZE method using 5% acetic acid as background electrolyte was applied to the separation of selenomethionine (SeM), selenocystine (SeC) and selenocystamine (SeCM). Depending on the species and the element, the detection limits of the CE/ICP-MS hyphenated system are up to 10² to 10³ times better than that for the CE/ESI-MS system.     

Analytical plasma source mass spectrometry in biomedical research

The features of inductively coupled plasma - mass spectrometry (ICP-MS) that make it unique also make possible applications in biological chemistry and biomedical research that would be otherwise difficult or impossible. High sensitivity, characterized spectral interferences, rapid mass scanning, and individual isotope measurements are now combined with sophisticated sample preparation, separations, or stable isotope additions to achieve rapid semi-quantitative analysis, element speciation, and high accuracy. The semi-quantitative analysis of various materials, the separation and detection of macromolecules in blood and other tissues, and tracking of stable isotopes added either purposely or inadvertently to children are important applications of ICP-MS. Current functional limitations and obstacles and potential development areas also are examined.     

Elemental speciation by chromatographic separation with inductively coupled plasma mass spectrometry detection

Separation techniques coupled to inductively coupled plasma mass spectrometry (ICP-MS) is reviewed. ICP-MS technique is described briefly. Coupling of the different separation techniques are described, together with the most common applications used for each technique that has been described in the literature. An overview for the future of separation techniques coupled to ICP-MS with regard to elemental speciation is discussed.     

Applications of inductively coupled plasma mass spectrometry and laser ablation inductively coupled plasma mass spectrometry in materials science

Inductively coupled plasma mass spectrometry (ICP-MS) and laser ablation ICP-MS (LA-ICP-MS) have been applied as the most important inorganic mass spectrometric techniques having multielemental capability for the characterization of solid samples in materials science. ICP-MS is used for the sensitive determination of trace and ultratrace elements in digested solutions of solid samples or of process chemicals (ultrapure water, acids and organic solutions) for the semiconductor industry with detection limits down to sub-picogram per liter levels. Whereas ICP-MS on solid samples (e.g. high-purity ceramics) sometimes requires time-consuming sample preparation for its application in materials science, and the risk of contamination is a serious drawback, a fast, direct determination of trace elements in solid materials without any sample preparation by LA-ICP-MS is possible. The detection limits for the direct analysis of solid samples by LA-ICP-MS have been determined for many elements down to the nanogram per gram range. A deterioration of detection limits was observed for elements where interferences with polyatomic ions occur. The inherent interference problem can often be solved by applying a double-focusing sector field mass spectrometer at higher mass resolution or by collision-induced reactions of polyatomic ions with a collision gas using an ICP-MS fitted with collision cell. The main problem of LA-ICP-MS is quantification if no suitable standard reference materials with a similar matrix composition are available. The calibration problem in LA-ICP-MS can be solved using on-line solution-based calibration, and different procedures, such as external calibration and standard addition, have been discussed with respect to their application in materials science. The application of isotope dilution in solution-based calibration for trace metal determination in small amounts of noble metals has been developed as a new calibration strategy. This review discusses new analytical developments and possible applications of ICP-MS and LA-ICP-MS for the quantitative determination of trace elements and in surface analysis for materials science.     

Analytical plasma source mass spectrometry in biomedical research

The features of inductively coupled plasma– mass spectrometry (ICP-MS) that make it unique also make possible applications in biological chemistry and biomedical research that would be otherwise difficult or impossible. High sensitivity, characterized spectral interferences, rapid mass scanning, and individual isotope measurements are now combined with sophisticated sample preparation, separations, or stable isotope additions to achieve rapid semi-quantitative analysis, element speciation, and high accuracy. The semi-quantitative analysis of various materials, the separation and detection of macromolecules in blood and other tissues, and tracking of stable isotopes added either purposely or inadvertently to children are important applications of ICP-MS. Current functional limitations and obstacles and potential development areas also are examined.     

Functional speciation of metal-dissolved organic matter complexes by size exclusion chromatography coupled to inductively coupled plasma mass spectrometry and deconvolution analysis

High performance size exclusion chromatography coupled to inductively coupled plasma mass spectrometry (HP-SEC–ICP-MS), in combination with deconvolution analysis, has been used to obtain multielemental qualitative and quantitative information about the distributions of metal complexes with different forms of natural dissolved organic matter (DOM). High performance size exclusion chromatography coupled to inductively coupled plasma mass spectrometry chromatograms only provide continuous distributions of metals with respect to molecular masses, due to the high heterogeneity of dissolved organic matter, which consists of humic substances as well as biomolecules and other organic compounds. A functional speciation approach, based on the determination of the metals associated to different groups of homologous compounds, has been followed. Dissolved organic matter groups of homologous compounds are isolated from the aqueous samples under study and their high performance size exclusion chromatography coupled to inductively coupled plasma mass spectrometry elution profiles fitted to model Gaussian peaks, characterized by their respective retention times and peak widths. High performance size exclusion chromatography coupled to inductively coupled plasma mass spectrometry chromatograms of the samples are deconvoluted with respect to these model Gaussian peaks. This methodology has been applied to the characterization of metal–dissolved organic matter complexes in compost leachates. The most significant groups of homologous compounds involved in the complexation of metals in the compost leachates studied have been hydrophobic acids (humic and fulvic acids) and low molecular mass hydrophilic compounds. The environmental significance of these compounds is related to the higher biodegradability of the low molecular mass hydrophilic compounds and the lower mobility of humic acids. In general, the hydrophilic compounds accounted for the complexation of around 50% of the leached metals, with variable contributions of humic and fulvic acids, depending on the nature of the samples and the metals.     

Inductively coupled plasma mass spectrometry in separation techniques: recent trends in phosphorus speciation

Inductively coupled plasma-MS (ICP-MS) and its combined use with molecular mass spectrometric techniques have become the most promising detection techniques in speciation studies. High sensitivity and element specificity of ICP-MS has the advantage of detecting trace amounts of the species of interest in complex matrices. This review is divided into two parts. In the first part, suitable use of ICP-MS either online or offline with currently used separation techniques such as HPLC, CE, and gel electrophoresis in speciation analysis is briefly discussed. In the second part, recent applications (1999-2005) of phosphorus speciation is presented to elucidate the importance of ICP-MS in separation methods and to illustrate its importance in nonmetal detection.     

Frontiers in elemental analysis by mass spectrometry

New developments in inductively coupled plasma mass spectrometry (ICP-MS) and laser desorption-time-of-flight mass spectrometry (LD-TOF-MS) for inorganic analysis are described. These include fundamental studies of the ion extraction, process in ICP-MS, development of a highly efficient nebulizer, isotope tracer studies, measurement of elemental speciation by liquid chromatography with ICP-MS detection and characterization of the structures of solids by ion association. The possibilities of determining inorganic species in solutions by electrospray MS are also described.     

Selenium speciation analysis using inductively coupled plasma-mass spectrometry

Selenium exists in several oxidation states and a variety of inorganic and organic compounds, and the chemistry of selenium is complex in both the environment and living systems. Selenium is an essential element at trace levels and toxic at greater levels. Interest in speciation analysis for selenium has grown rapidly in this last decade, especially in the use of chromatographic separation coupled with inductively coupled plasma-mass spectrometry (ICP-MS). Complete characterization of selenium compounds is necessary to understand selenium's significance in metabolic processes, clinical chemistry, biology, toxicology, nutrition and the environment. This review describes some of the essential background of selenium, and more importantly, some of the currently used separation methodologies, both chromatographic and electrophoretic, with emphasis on applications of selenium speciation analysis using ICP-MS detection.     

Applications of mass spectrometry in the trace element analysis of biological materials

The importance of mass spectrometry for the analysis of biological material is illustrated by reviewing the different mass spectrometric methods applied and describing some typical applications published recently. Though atomic absorption spectrometry is used in the majority of analyses of biological material, most mass spectrometric methods have been used to some extent for trace element determination in biomedical research. The relative importance of the different methods is estimated by reviewing recent research papers. It is striking that especially inductively coupled plasma mass spectrometry is increasingly being applied, partly because the method can be used on-line after chromatographic separation, in speciation studies. Mass spectrometric methods prove to offer unique possibilities in stable isotope tracer studies and for this purpose also experimentally demanding methods such as thermal ionization mass spectrometry and accelerator mass spectrometry are frequently used.     

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.     

Environmental application of elemental speciation analysis based on liquid or gas chromatography hyphenated to inductively coupled plasma mass spectrometry—A review

In recent years the number of environmental applications of elemental speciation analysis using inductively coupled plasma mass spectrometry (ICP-MS) as detector has increased significantly. The analytical characteristics, such as extremely low detection limits (LOD) for almost all elements, the wide linear range, the possibility for multi-elemental analysis and the possibility to apply isotope dilution mass spectrometry (IDMS) make ICP-MS an attractive tool for elemental speciation analysis. Two methodological approaches, i.e. the combination of ICP-MS with high performance liquid chromatography (HPLC) and gas chromatography (GC), dominate the field. Besides the investigation of metals and metalloids and their species (e.g. Sn, Hg, As), representing “classic” elements in environmental science, more recently other elements (e.g. P, S, Br, I) amenable to ICP-MS determination were addressed. In addition, the introduction of isotope dilution analysis and the development of isotopically labeled species-specific standards have contributed to the success of ICP-MS in the field. The aim of this review is to summarize these developments and to highlight recent trends in the environmental application of ICP-MS coupled to GC and HPLC.     

High-performance liquid chromatography of selenium compounds utilizing perfluorinated carboxylic acid ion-pairing agents and inductively coupled plasma and electrospray ionization mass spectrometric detection

Increasing speciation demands in clinical chemistry, toxicology and nutrition have made the determination of the total elements in a sample inadequate; the amount of an element and the chemical forms in which it is present need to be known. Inductively coupled plasma mass spectrometry (ICP-MS) was used after high-performance liquid chromatographic (HPLC) separation, as was electrospray ionization mass spectrometry (ESI-MS). The effect of variation of the number of carbon atoms in perfluorinated carboxylic acids used as ion-pairing agents for the separation of selenium compounds was examined. Trifluoroacetic acid (0.1%), pentafluoropropanoic acid (0.1%) or heptafluorobutanoic acid (0.1%; HFBA) were alternatively used as additives to methanol-water (1:99, v/v) solutions as mobile phases. Reversed-phase HPLC-ICP-MS with 0.1% HFBA in the mobile phase allowed more than 20 selenium compounds to be separated in 70 min in an isocratic elution mode; the separation of natural selenium-enriched sample extracts was examined and explained. The pH of the 0.1% HFBA solution was modified with hydrochloric acid or ammonia and the pH of the sample extracts before injection was modified in order to overcome unwanted double peak formation in the chromatograms of sample extracts. Oxidations of standard gamma-glutamyl-Se-methylselenocysteine and Se-methylselenocysteine were carried out using 30% H2O2 solution and identifications of selenium-containing oxidation products were made using HPLC-ICP-MS and HPLC-ESI-MS. The principal organic oxidation product in both cases was methaneseleninic acid (MeSeO2H).     

Electrospray mass spectrometry: a tool for elemental speciation

Recent progress in the development of electrospray mass spectrometry (ESMS) as a tool for elemental speciation is reviewed. Reports wherein ESMS is used to qualitatively determine the presence of metal ions (inorganic, organometallic and complexed) and non-metallic inorganic species have grown exponentially over the last decade. In addition to elemental speciation, impact in other areas such as gas-phase chemistry, inorganic–organometallic chemistry and biological mass spectrometry has been prolific. The review is structured to cover each of the areas listed above, and also includes a brief introduction, discussion of the electrospray process, discussion of instrumentation and other relevant application areas. An overview of the types of species/complexes studied is given in each section along with a brief discussion of the application objectives and analytical aspects. Analytical considerations for the development of ESMS as a tool for elemental speciation are also raised, including, application, quantitation, sensitivity, limitations and future directions. The impact of speciation strategies involving stand-alone ESMS, ESMS coupled with on-line separation techniques and the inclusion of ESMS in dual (multiple) technique strategies are presented. High backgrounds due to chemical noise and signal suppression (matrix effects) appear to be two important factors limiting sensitive detection of most analytes. The use of sample pre-treatment, pre-concentration or separation techniques is necessary to alleviate these problems. Although ESMS currently suffers from a number of limitations, continued instrumentation and methods development will improve its capability and diversify the impact of ESMS as a tool for elemental speciation.     

Comparative study of atomic fluorescence spectroscopy and inductively coupled plasma mass spectrometry for mercury and arsenic multispeciation

Mercury and arsenic are two elements of undoubted importance owing to their toxic character. Although speciation of these elements has been developed separately, in this work for the first time the speciation of As and Hg using two atomic fluorescence detectors in a sequential ensemble is presented. A coupling based on the combination of high-performance liquid chromatography (where mercury and arsenic species are separated) and two atomic fluorescence detectors in series, with several online treatments, including photooxidation (UV) and hydride generation, has allowed the determination of mercury and arsenic compounds simultaneously. The detection limits for this device were 16, 3, 17, 12 and 8 ng mL^–1 for As^III, monomethylarsinic acid, As^V, Hg²⁺ and methylmercury, respectively. This coupling was compared with an analogous one based on inductively coupled plasma–mass spectrometry (ICP-MS) detection, with detection limits of 0.7, 0.5, 0.8, 0.9 and 1.1 ng mL^–1, respectively. Multispeciation based on ICP-MS exhibits better sensitivity than the coupling based on tandem atomic fluorescence, but this second device is a very robust system and exhibits obvious advantages related to the low cost of acquisition and maintenance, as well as easy handling, which makes it a suitable system for routine laboratories.     

The potential and challenges of elemental speciation by capillary electrophoresis-inductively coupled plasma mass spectrometry and electrospray or ion spray mass spectrometry

Capillary electrophoresis-inductively coupled plasma mass spectrometry (CE-ICP-MS) and electrospray (ES) or ion spray (IS) mass spectrometry (MS) are recently introduced techniques for elemental speciation. Both techniques have the potential for rapid elemental speciation with low detection limits. Examples of the use of CE-ICP-MS for elemental speciation of positive, neutral and negative species are discussed. Issues in interfacing CE and ICP-MS are considered briefly. The potential advantages and disadvantages of laminar flow in CE-ICP-MS are examined. Potential difficulties in CE-ICP-MS including loss of sample, chemical matrix effects and changes in speciation during separation are discussed. The interpretation of ES or IS-MS spectra and analysis of complex mixtures are considered. Calibration and chemical matrix effects are assessed. Potential pitfalls of interpreting bare metal ion spectra as elemental analysis are discussed. The need for fundamental understanding of the processes that control ES and IS-MS signals is examined. High conductivity samples currently present difficulties for CE-ICP-MS or ES and IS-MS.     

Urinary selenium speciation by high-performance liquid chromatography-inductively coupled plasma mass spectrometry: advantages of detection with a double-focusing mass analyser with a hydride generation interface

A detailed comparison of the performance of inductively coupled plasma mass spectrometry (ICP-MS), with quadrupole and double-focusing instruments for the speciation of selenium in urine has been carried out. Selenium sensitivity about 23-59 times higher with double-focusing ICP-MS detection was observed, but limits of detection were only 1-8.7 times better because of background noise. Selenium species separation has been carried out by both reversed-phase and vesicle-mediated high-performance liquid chromatography (HPLC), coupled on-line with the detector via conventional nebulization and via on-line focused microwave digestion-hydride generation. A remarkable improvement in sensitivity (28-110 times better for (77)Se depending on the chromatographic system) and elimination of interference problems from the urinary matrix or the components of the mobile phases were achieved when an on-line microwave digestion-hydride generation interface was used, but the background noise was much higher than with conventional nebulization. Therefore, the limits of detection were not as low as expected from such improvement in the sensitivity. More selenocompounds can be separated, and a slight improvement in the sensitivity and limits of detection was obtained when the vesicle-mediated HPLC system was used as compared with reverse-phase chromatography. However, the use of several complementary chromatographic systems, such as reverse-phase HPLC, is recommended to bring some light on the selenocompounds present in basal human urine. Comparative data of rat urine speciation are also given.