Accuracy mass spectrometry

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. 

K. Blaum. High-Accuracy Mass Spectrometry with Stored Ions. Physics Reports, 425(2006) 1-78. 

The mass difference a single electron makes is observable using high-accuracy mass spectrometry. Table 13.12 lists the atomic weight of a proton, neutron, and electron. Table 13.13 lists selected isotopes along with their atomic number, atomic weight, monoisotopic mass, and relative abundance. 

The starting point for mass spectrometric characterizations is often the determination of the molecular weight. If the impurity arose after exposure to oxygen and a mass shift of 16 is observed between the drug substance and the impurity, it can be concluded that the impurity is oxidized drug substance. High mass accuracy mass spectrometry may also be used for molecular formula determination. 

High Mass Accuracy Mass Spectrometry Approach... 

Thomas, A., Schanzer, W., Delahaut, R, and Thevis, M. (2009) Sensitive and fast identification of urinary human, synthetic and animal insulin by means of nano-UPLC coupled with high resolution/high accuracy mass spectrometry. Drug Testing and Analysis, 1,219-227. 

The spectroscopic methods, NMR and mass spectrometry for predicting cetane numbers have been established from correlations of a large number of samples. The NMR of carbon 13 or proton (see Chapter 3) can be employed. In terms of ease of operation, analysis time (15 minutes), accuracy of prediction (1.4 points average deviation from the measured number), it is... 

With regard to mass spectrometry, accuracy is not as high with an average error of 2.8 points, but on the other hand, the sample required is very small, being around 2 jl1. 

Samples to be examined by inductively coupled plasma and mass spectrometry (ICP/MS) are commonly in the form of a solution that is transported into the plasma flame. The thermal mass of the flame is small, and ingress of excessive quantities of extraneous matter, such as solvent, would cool the flame and might even extinguish it. Even cooling the flame reduces its ionization efficiency, with concomitant effects on the accuracy and detection limits of the ICP/MS method. Consequently, it is necessary to remove as much solvent as possible which can be done by evaporation off-line or done on-line by spraying the solution as an aerosol into the plasma flame. 

However, interpretation of, or even obtaining, the mass spectrum of a peptide can be difficult, and many techniques have been introduced to overcome such difficulties. These techniques include modifying the side chains in the peptide and protecting the N- and C-terminals by special groups. Despite many advances made by these approaches, it is not always easy to read the sequence from the mass spectrum because some amide bond cleavages are less easy than others and give little information. To overcome this problem, tandem mass spectrometry has been applied to this dry approach to peptide sequencing with considerable success. Further, electrospray ionization has been used to determine the molecular masses of proteins and peptides with unprecedented accuracy. 

Oils are mixtures of mixed esters with different fatty acids distributed among the ester molecules. Generally, identification of specific esters is not attempted instead the oils are characterized by analysis of the fatty acid composition (8,9). The principal methods have been gas—Hquid and high performance Hquid chromatographic separation of the methyl esters of the fatty acids obtained by transesterification of the oils. Mass spectrometry and nmr are used to identify the individual esters. It has been reported that the free fatty acids obtained by hydrolysis can be separated with equal accuracy by high performance Hquid chromatography (10). A review of the identification and deterrnination of the various mixed triglycerides is available (11). 

The complex of the following destmctive and nondestmctive analytical methods was used for studying the composition of sponges inductively coupled plasma mass-spectrometry (ICP-MS), X-ray fluorescence (XRF), electron probe microanalysis (EPMA), and atomic absorption spectrometry (AAS). Techniques of sample preparation were developed for each method and their metrological characteristics were defined. Relative standard deviations for all the elements did not exceed 0.25 within detection limit. The accuracy of techniques elaborated was checked with the method of additions and control methods of analysis. 

The analytical techniques covered in this chapter are typically used to measure trace-level elemental or molecular contaminants or dopants on surfaces, in thin films or bulk materials, or at interfaces. Several are also capable of providing quantitative measurements of major and minor components, though other analytical techniques, such as XRF, RBS, and EPMA, are more commonly used because of their better accuracy and reproducibility. Eight of the analytical techniques covered in this chapter use mass spectrometry to detect the trace-level components, while the ninth uses optical emission. All the techniques are destructive, involving the removal of some material from the sample, but many different methods are employed to remove material and introduce it into the analyzer. 

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. 

Because GDMS can provide ultratrace analysis with total elemental coverage, the technique fills a unique analytical niche, supplanting Spark-Source Mass Spectrometry (SSMS) by supplying the same analysis with an order-of-magnitude better accuracy and orders-of-magnitude improvement in detection limits. GDMS analy-... 

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. 

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