Isotope-dilution mass spectrometry principles

Isotope-Dilution Mass Spectrometry—Principle and Scope. 113... 

Isotope dilution mass spectrometry— a principle of measurement suitable for establishing reference procedures... 

The book offers the reader in its first part a general and as detailed as necessary introduction into the basic principles and methods, starting with sampling, sample storage and sample treatment. These steps are of utmost importance for each analytical procedure. This is followed by the description of the potential of a number of modern trace analytical methods, i.e. atomic absorption and emission spectrometry, voltammetry, neutron activation and isotope dilution mass spectrometry. The latter method is an important reference method within a general concept for quality control and the generation of reference materials which are an absolute must in this context. 

Some analytes are difficult to standardize owing to the complexity of developing a primary standard, or analyte inhomogeneity, an International Standard is used to provide comparability. Such standards are based on the principle of transferability. A definitive method, e.g., isotope-dilution mass spectrometry (MS), is used to obtain the best possible estimate of the accurate concentration of the analyte. This value would be transferred to a reference method, which is usually a very carefully documented analytical procedure of known and impeccable performance, e.g., Abel-Kendal assay for cholesterol, and standards are compared in the procedure before being used in the filed. 

Spectrophotometric methods generally have lost their significance. Nevertheless in particular analyzers spectrophotometry is applied due to the simple practicability of the technique, less in the determination of sodium and potassium [24] but more frequently in the determination of calcium (e.g., Cresolphthalein). In calcium determination atomic absorption spectrometry (AAS) yields accurate results, so this method is used as reference method. Further alternative methods are ion chromatography [25] and isotope dilution-mass spectrometry. A rapid assay for determination of potassium is based on the principle of turbidimetry [26]. 

Chapter 8 provides the reader with the basic principles of isotope dilution mass spectrometry used for elemental analysis and also discusses more advanced features of this calibration approach, such as its use in direct solid sample analysis and in elemental speciation work, wherein not the total amount but that of various chemical species of a target element need to be determined. 

For the determination of isotope ratios, the precision of TOF-ICP-MS has been studied in a preliminary comparison with other mass spectrometer systems [643]. Typical isotope ratio precisions of 0.05% were obtained, thus overtaking sector field mass spectrometry with sequential detection, for which values of 0.1-0.3% for Cu/ Cu in Antarctic snow samples have been reported [644]. Similar results were obtained by Becker et al. [645] for Mg and Ca in biological samples (0.4-0.5%). In principle, the features of TOF-ICP-MS may be superior to those of sequential sector field or quadrupole mass spectrometry however, true parallel detection of the signals, as is possible with multi-collector systems or array detector mass spectrometry, may be the definitive solution, as shown by Hirata et al. [646]. Here, the use of detectors which allow true parallel measurement of the signals within the relevant mass range, just as the CCDs do for optical atomic spectrometry, may be the ultimate solution and bring about the final breakthrough for ICP-MS isotope ratio measurements as is required in isotope dilution mass spectrometry. 

This demonstration is intended to show how quantification is achieved using isotope dilution principles in mass spectrometry (Fig. 14.5). It also shows the issue of error in clinical measurements, such as precision accuracy and the use of relative relationships of one compound to another. 

In the past decade, eight inherited disorders have been linked to specific enzyme defects in the isoprenoid/cholesterol biosynthetic pathway after the finding of abnormally increased levels of intermediate metabolites in tissues and/or body fluids of patients (Table 5.1.1) [7, 9, 10]. Two of these disorders are due to a defect of the enzyme mevalonate kinase, and in principle affect the synthesis of all isoprenoids (Fig. 5.1.1) [5]. The hallmark of these two disorders is the accumulation of mevalonic acid in body fluids and tissues, which can be detected by organic acid analysis, or preferably, by stable-isotope dilution gas chromatography (GC)-mass spectrometry (GC-MS) [2]. Confirmative diagnostic possibilities include direct measurement of mevalonate kinase activities in white blood cells or primary skin fibroblasts [3] from patients, and/or molecular analysis of the MVK gene [8]. 

An excellent possibility for quantifying analytical data in inorganic mass spectrometry is isotope dilution analysis (IDA) based on more precise isotope ratio measurements. IDA uses highly enriched isotope spikes of analytes of known concentration for calibration and is the method of choice if a high accuracy for element concentrations is required. The principles and applications of this method will be discussed below. 

The principle of the isotope dilution analysis (IDA) is described in Section 6.4. Due to its advantages as a definitive and accurate analytical method for the determination of element concentration via isotope ratio measurements, IDA is being increasingly applied in mass spectrometry, especially in ICP-MS and LA-ICP-MS as one of the most frequently used techniques. For example, the isotope dilution technique is employed in species analysis in biological systems, " e.g., for the determination of mercury species in tuna material,or in aquatic systems. Further applications of the isotope dilution technique are the determination of selenomethionine in human blood serum by capillary HPLC-ICP (ORC) MS ° or sulfur speciation in gas oil, diesel or heating fuel by LA-ICP-MS. Evans and co-workers have reported on the high accuracy analysis of sulfur in diesel fuel by IDA. ICP-SFMS has been employed for Si species analysis in biological or clinical samples and... 

One of the main characteristics of mass spectrometry is the possibility of precise and accurate isotope ratio measurements. The isotopic dilution technique is based on the principle that most elements in natme possess fixed isotopic ratios. This natural ratio can be altered by spiking a sample with an analyte standard consisting of a different isotopic abundance. The change in the measured isotopic ratio can then be used to elucidate the original elemental composition of the sample. The only real requirements of this technique are that the analyte... 

See also Atomic Absorption Spectrometry Interferences and Background Correction. Atomic Emission Spectrometry Principles and Instrumentation Interferences and Background Correction Flame Photometry Inductively Coupled Plasma Microwave-Induced Plasma. Atomic Mass Spectrometry Inductively Coupled Plasma Laser Microprobe. Countercurrent Chromatography Solvent Extraction with a Helical Column. Derivatization of Analytes. Elemental Speciation Overview Practicalities and Instrumentation. Extraction Solvent Extraction Principles Solvent Extraction Multistage Countercurrent Distribution Microwave-Assisted Solvent Extraction Pressurized Fluid Extraction Solid-Phase Extraction Solid-Phase Microextraction. Gas Chromatography Ovenriew. Isotope Dilution Analysis. Liquid Chromatography Ovenriew. 

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