Mass spectrometry precision

Johnson KL, Mason CJ, Muddiman DC, Eckel JE (2004) Analysis of the low molecular weight fraction of serum by LC-dual ESI-FT-ICR mass spectrometry Precision of retention time, mass, and ion abundance. Anal Chem 76 5097-5103. 

The best mass spectrometry precision for measurement of a ratio is usually achieved with isotope amount ratio measurements close to unity. Hence silver was used by Begley and Sharps for their fundamental studies in order to exploit the advantages of a natural 1 1 system. However, it is generally acknowledged that modest deviations, by a factor of 3 or 4, from this optimum are unlikely to degrade the overall performance by a significant degree. 

Brand WA (1998) Isotope ratio mass spectrometry precision from transient signals. In Advances in Mass Spectrometry. Karajalainen EJ, Hesso AE, Jalonen JE and Karjalainen UP (eds), Vol 14, pp 655 680. Amsterdam Elsevier. 

Present day techniques for structure determination in carbohydrate chemistry are sub stantially the same as those for any other type of compound The full range of modern instrumental methods including mass spectrometry and infrared and nuclear magnetic resonance spectroscopy is brought to bear on the problem If the unknown substance is crystalline X ray diffraction can provide precise structural information that m the best cases IS equivalent to taking a three dimensional photograph of the molecule... 

The previous discussion has centered on how to obtain as much molecular mass and chemical structure information as possible from a given sample. However, there are many uses of mass spectrometry where precise isotope ratios are needed and total molecular mass information is unimportant. For accurate measurement of isotope ratio, the sample can be vaporized and then directed into a plasma torch. The sample can be a gas or a solution that is vaporized to form an aerosol, or it can be a solid that is vaporized to an aerosol by laser ablation. Whatever method is used to vaporize the sample, it is then swept into the flame of a plasma torch. Operating at temperatures of about 5000 K and containing large numbers of gas ions and electrons, the plasma completely fragments all substances into ionized atoms within a few milliseconds. The ionized atoms are then passed into a mass analyzer for measurement of their atomic mass and abundance of isotopes. Even intractable substances such as glass, ceramics, rock, and bone can be examined directly by this technique. 

Historically, the term SIMS was developed for bombardment of solid surfaces with ions, so, for greater descriptive precision, the name liquid secondary ion mass spectrometry (LSIMS) is better and can be used synonymously with FAB,... 

Tandem mass spectrometry (MS/MS) produces precise structural or sequence information by selective and specific induced fragmentation on samples up to several thousand Daltons. For samples of greater molecular mass than this, an enzyme digest will usually produce several peptides of molecular mass suitable for sequencing by mass spectrometry. The smaller sequences can be used to deduce the sequence of the whole protein. 

The abundance of a trace element is often too small to be accurately quantihed using conventional analytical methods such as ion chromatography or mass spectrometry. It is possible, however, to precisely determine very low concentrations of a constituent by measuring its radioactive decay properties. In order to understand how U-Th series radionuclides can provide such low-level tracer information, a brief review of the basic principles of radioactive decay and the application of these radionuclides as geochronological tools is useful. " The U-Th decay series together consist of 36 radionuclides that are isotopes (same atomic number, Z, different atomic mass, M) of 10 distinct elements (Figure 1). Some of these are very short-lived (tj j 1 -nd are thus not directly useful as marine tracers. It is the other radioisotopes with half-lives greater than 1 day that are most useful and are the focus of this chapter. 

C. W. Magee. Critical Parameters Affecting Precision and Accuracy in Spark Source Mass Spectrometry with Electrical Detection. PhD thesis, Univetsity of Virginia, University Microfilms, Ann Arbot, MI, 1973. 

ICPMS is uniquely able to borrow a quantitation technique from molecular mass spectrometry. Use of the isotope dilution technique involves the addition of a spike having a different isotope ratio to the sample, which has a known isotope ratio. This is usefiil for determining the concentration of an element in a sample that must undergo some preparation before analysis, or for measuring an element with high precision and accuracy. ... 

Another advantage of mass spectrometry is its sensitivity - a full-scan spectrum, and potentially an identification, can be obtained from picogram (pg) amounts of analyte. In addition, it may be used to provide quantitative information, usually to low levels, with high accuracy and precision. 

Quantitative methodology employing mass spectrometry usually involves selected-ion monitoring (see Section 3.5.2.1) or selected-decomposition monitoring (see Section 3.4.2.4) in which a small number of ions or decompositions of ions specific to the compound(s) of interest are monitored. It is the role of the analyst to choose these ions/decompositions, in association with chromatographic performance, to provide sensitivity and selectivity such that when incorporated into a method the required analyses may be carried out with adequate precision and accuracy. 

Adequate precision and accuracy are only likely to be achieved if some standardization procedure is employed and the nature of this, internal or external standards or the method of standard additions, needs to be chosen carefully. If internal standardization procedures are adopted then appropriate compound(s) must be chosen and their effect on the chromatographic and mass spectrometry methods assessed. The ideal internal standard is an isotopically labelled analogue of the analyte but, although there are a number of commercial companies who produce a range of such molecules, these are not always readily available. An analytical laboratory is then faced with the choice of carrying out the synthesis of the internal standard themselves or choosing a less appropriate alternative with implications on the accuracy and precision of the method to be developed. 

Table 5.20 Intra-assay precision and accuracy of the LC-ToF-MS determination of Idoxifene. Reprinted from J. Chromatogr, B, 757, Comparison between liquid chromatography-time-of-flight mass spectrometry and selected-reaction monitoring liquid chromatography-mass spectrometry for quantitative determination of Idoxifene in human plasma , Zhang, H. and Henion, J., 151-159, Copyright (2001), with permission from Elsevier Science...

Eichelberger JW, Kerns EH, Olynyk P, et al. 1983. Precision and accuracy in the determination of organics in water by fused silica capillary column gas chromatography/mass spectrometry and packed column gas chromatography/mass spectrometry. Anal Chem 55 1471-1479. 

Different isotopes differ in their atomic masses. The intensities of the signals from different isotopic ions allow isotopic abundances to be determined with high accuracy. Mass spectrometry reveals that the isotopic abundances in elemental samples from different sources have slightly different values. Isotopic ratios vary because isotopes with different masses have slightly different properties for example, they move at slightly different speeds. These differences have tiny effects at the level of parts per ten thousand (0.0001). The effects are too small to appear as variations In the elemental molar masses. Nevertheless, high-precision mass spectrometry can measure relative abundances of isotopes to around 1 part in 100,000. 

Several methods are available for the analysis of trichloroethylene in biological media. The method of choice depends on the nature of the sample matrix cost of analysis required precision, accuracy, and detection limit and turnaround time of the method. The main analytical method used to analyze for the presence of trichloroethylene and its metabolites, trichloroethanol and TCA, in biological samples is separation by gas chromatography (GC) combined with detection by mass spectrometry (MS) or electron capture detection (ECD). Trichloroethylene and/or its metabolites have been detected in exhaled air, blood, urine, breast milk, and tissues. Details on sample preparation, analytical method, and sensitivity and accuracy of selected methods are provided in Table 6-1. 

CANFIELD w K (1993). Study of beta-carotene metabolism in humans using 13C-beta-carotene and high precision isotope ratio mass spectrometry. Annals of the New York Academy of Sciences 691 86-95. 

For precise measurement of isotopic composition by mass spectrometry, it is also common to use either a natural, known isotopic ratio to correct for instrumental mass fractionation (e g., internal normalization) or to add a tracer for this purpose. For example for natural uranium samples, one can use the natural U/ U of 137.88 to correct for fractionation. Alternatively, one can use an added double spike of ratio -unity... 

An alternative to the bridge technique was recently reported for thorium analysis in silicate rocks for which both Th and Th are measured on a single lon-counting detector (Rubin 2001). With careful chemistry and mass spectrometry, °Th/ Th ratios of igneous rocks can be measured with this technique with a precision that is similar to the bridge method. The disadvantage of this technique is that °Th ion-count rates are extremely low (around 10 cps) with normal silicate thorium ratios and are therefore subject to perturbations from background variation and low-level isobaric interferences in normal samples. 

Multiple-collector inductively coupled plasma mass spectrometry (MC-ICPMS) combines sector-field ICPMS with a multiple collector detector system and has recently emerged as an alternative to TIMS for precise U-Th isotope measurement. The full potential of MC-ICPMS has yet to be realized. Yet despite this, its performance in high precision isotope measurement already challenges and, in some cases, surpasses that ever achieved by TIMS (e.g., Lee and Halliday 1995 Blichert-Toft and Albarede 1997). 

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