Isotope internal calibration

The mass accuracy is highly dependent on the mode the instrument is operating in. In the reflector mode, with time-lag focusing, the best MALDI-TOF and oa-TOF instruments are capable of achieving <5 ppm with internal standards, provided that the isotopes are resolved. In many cases it is not possible to add internal calibrants, and then the error in mass accuracy is often increased to 50-100 ppm. Operation of an instalment in a linear mode will typically decrease the mass accuracy. 

Table 2 Comparison of Cholesterol Reference Method Laborato- tute, NIST National Institute of Standards and Technology (US ry Network (CRMLN) traceability model to the International Or- NMI), IDMS isotope dilution mass spectrometry, ACL accredited ganization for Standardization (ISO) model. BIPM International calibration laboratory, AK Abell-Kendall Bureau of Weights and Measures, NMI National Metrology Insti-...

Quantitation of extraction under nonequilibrium conditions is based on the proportional relationship between the sorbed analyte and initial concentration [68]. Calibration of the SPME technique can be based on internal calibration using isotopically labeled standards or standard addition if recovery is matrix dependent. External calibration can be used if the standard matrix and the sample matrix are closely similar or identical [128,132,134],... 

Nilsson LB, Eklund G (2007) Direct quantification in bioanalytical LC-MS/MS using internal calibration via analyte/stable isotope ratio. J Pharm Biomed Anal 43 1094-1099... 

Quantitative Whole-Body Autoradiography (QWBA) is based on the RLG technique and the use of standards obtained from dilution series containing known concentrations of radioactivity. Isotopes used in QWBA are mainly 14C and 3H. These standards were cut together with the whole-body sections to ensure an identical thickness and used for the internal calibration. The information of the calibration curve allows the determination of the concentrations in the organs and tissues of interest which can be derived from the measured area and the section thickness. 

Assays requiring an internal calibration depend on the near identical behaviour of the calibration compound and the analyte. This is easily achieved by using an analogue of the analyte which has some protons in its stmcture replaced by deuterons. Provided that the deuterons are in such positions that they are stable to the analytical procedure and not back exchanged for proton, and do not affect the physical properties of the molecule (for instance changing the proton affinity) then the substitution of three or more protons will shift the deuterium labelled response clear from the isotopic peaks of the analyte due to natural and contributions. Such compounds act as excellent internal standards. Suitable labelling also enables the deuterium labelled compound to act as a carrier to improve recovery of the analyte at low levels (the so called stable isotope carrier effect [32]). 

Ion fractionation can be very effectively corrected by an internal calibration after spiking a uranium sample with a mixture of isotopes of certified ratio, like IRMM-3636 (Richter et al. 2008) or CETAMA-MIRF-02, or spiking a plutonium sample with a certified mixture of Pu and Pu isotopes. Several batches of mixtures of Pu, and Pu isotopes... 

Isotope dilution This relatively new calibration method is occasionally used in specialized forensic applications. The method affords exceptional accuracy and precision, but is limited by the availability of suitable standards. Although the use of deuterated internal standards is sometimes equated with isotope dilution, the techniques are not the same. Isotope-dilution calibration is based on the addition of standards that contained enriched levels of stable isotopes of common elements such as C. The enriched standard, referred to as the spike, is added to the sample and allowed to reach equilibrium. The sample is then analyzed via mass spectrometry. Because the spike is chemically identical to the target analyte, the matrix correction is as good as that achieved with standard-addition calibration. However, until enriched stable isotope analogs of forensic analytes are available and affordable, isotope dilution will not be widely applied in forensic chemistry. 

Stable isotope dilution mass-spectrometry (MSID) is the most accurate technique for determining lanthanide abundances in geochemical materials.. The superior quality of the method may be attributed principally to the inherent sensitivity of mass-spectrometers, and to the use of the ideal internal standard, namely, an artificially enriched isotope of each element to be determined. The utilization of isotopic internal standards virtually eliminates such potential analytical problems as quantitative recovery and instrument calibration. The sensitivity of the mass spectrometer is such that the lower limit of measurable abundance is usually controlled by the purity of the reagents used in preparing the sample for analysis. 

Quantitative mass spectrometry, also used for pharmaceutical appHcations, involves the use of isotopicaHy labeled internal standards for method calibration and the calculation of percent recoveries (9). Maximum sensitivity is obtained when the mass spectrometer is set to monitor only a few ions, which are characteristic of the target compounds to be quantified, a procedure known as the selected ion monitoring mode (sim). When chlorinated species are to be detected, then two ions from the isotopic envelope can be monitored, and confirmation of the target compound can be based not only on the gc retention time and the mass, but on the ratio of the two ion abundances being close to the theoretically expected value. The spectrometer cycles through the ions in the shortest possible time. This avoids compromising the chromatographic resolution of the gc, because even after extraction the sample contains many compounds in addition to the analyte. To increase sensitivity, some methods use sample concentration techniques. 

Abundances of lUPAC (the International Union of Pure and Applied Chemistry). Their most recent recommendations are tabulated on the inside front fly sheet. From this it is clear that there is still a wide variation in the reliability of the data. The most accurately quoted value is that for fluorine which is known to better than I part in 38 million the least accurate is for boron (1 part in 1500, i.e. 7 parts in [O ). Apart from boron all values are reliable to better than 5 parts in [O and the majority arc reliable to better than I part in 10. For some elements (such as boron) the rather large uncertainty arises not because of experimental error, since the use of mass-spcctrometric measurements has yielded results of very high precision, but because the natural variation in the relative abundance of the 2 isotopes °B and "B results in a range of values of at least 0.003 about the quoted value of 10.811. By contrast, there is no known variation in isotopic abundances for elements such as selenium and osmium, but calibrated mass-spcctrometric data are not available, and the existence of 6 and 7 stable isotopes respectively for these elements makes high precision difficult to obtain they are thus prime candidates for improvement. 

Residues of isoxaflutole, RPA 202248 and RPA 203328 are extracted from surface water or groundwater on to an RP-102 resin solid-phase extraction (SPE) cartridge, then eluted with an acetonitrile-methanol solvent mixture. Residues are determined by liquid chromatography/tandem mass spectrometry (LC/MS/MS) on a Cg column. Quantitation of results is based on a comparison of the ratio of analyte response to isotopically labeled internal standard response versus analyte response to internal standard response for calibration standards. 

Libby, L. M., Pandolfi, L. J., Calibration of Two Isotope Thermometers in a European Oak Using Official Weather Records, Proceedings of International CLIMAP Conference, Norwich, England, 1973, 21-39. 

Quantification is usually achieved by a standard addition method, use of labeled internal standards, and/or external calibration curves. In order to allow for matrix interferences the most reliable method for a correct quantitation of the analytes is the isotope dilution method, which takes into account intrinsic matrix responses, using a deuterated internal standard or carbon-13-labeled internal standard with the same chemistry as the pesticide being analyzed (i.e., d-5 atrazine for atrazine analysis). Quality analytical parameters are usually achieved by participation in interlaboratory exercises and/or the analysis of certified reference materials [21]. 

Natural abundance data are nearly always reported as delta values, 5 in units of per mil ( mil = 1000), written %o. This is a relative measurement made against a laboratory s own reference material, a working standard , calibrated against an international standard. Delta values are calculated from measured isotope ratio as ... 

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