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The current criteria are not based on objective or empirical forms of measurement, but are based on arbitrary criteria using subjective assessments about the degree of selectivity provided by different MS techniques. The assessments are generally correct, but there are many exceptions, depending on the analyte-matrix pair, the concentration, the MS ions detected, the analytical technique, and the importance of the results.
The current rates of false negatives are thought to be too high in both types of application (enforcement and non-enforcement) because the identification criteria are too stringent. Furthermore, spurious errors are not typically addressed to reduce false positives, which are best addressed through confirmatory analysis.
As the word implies, ¡®¡®confirmation¡¯¡¯ requires the results from at least two analyses (which should ideally be orthogonally selective and at least one of them should involve MS detection after an analytical separation), which, in enforcement applications, must agree with each other in terms of analyte identity and concentration.
For non-enforcement purposes, a single analysis using MS detection should be satisfactory, or two analyses using non-MS methods, provided that there has been an empirical demonstration that acceptably low rates of false positives and false negatives occur for the analytes at an adequately low concentration in the targeted matrices. An MS qualitative screening approach may be the best option, followed by a different method to make the confirmation and to improve the quantitative determination.
We summarize the arguments and the points made in this article in the following proposed sequence for quantitative and qualitative method validation.
(1) Define the need for the analysis (scope of analytes and matrices, concentration ranges, acceptable degree of accuracy, and tolerable rate of false negatives);
(2) Define the primary analytical method(s) to meet the needs of the analysis most effectively and efficiently (e.g., GC-MS, LC-MS2, GC with selective detection, LC-fluorescence, and others);
(3) Conduct method validation of the primary method(s) for the targeted analyte(s) and matrix(es) (or representative analytes and matrices) to determine quantitative characteristics of the method(s) according to accepted practices;
(4) At the same time as quantitative method validation, empirically determine MS criteria using samples of known concentrations on different days in fortified matrices to achieve the desired identification limit (with set criteria to minimize false negatives);
(5) Measure rates of false positives while also training analysts through analysis of blind fortification samples(P10¨C20 blanks from different sources and a similar number of fortified samples at a variety of concentrations); [Note: this can be done over time during routine analyses, and such tests should be part of the QC requirements];
(6) Devise a second approach to be used for independent confirmation of suspected violative samples from the initial analysis, and conduct blind analyses of extracts to estimate rates of false positives and false negatives vs concentration, as in Step (5).
The proposed validation sequence covers only general factors, but, in future, we hope that more specific, practical procedures can be described, just as in the case of quantitative method validation for chemical residue analysis. Further scientific study of the degree of selectivity of MS techniques coupled with analytical separations is needed. Ideally, a systematic approach based on sound theory can be devised to assess accurately the degree of accuracy in qualitative MS analysis, but, until that time, we believe that the proposed general approach is more scientific and better fits the purposes of chemical-residue analysis than the arbitrary criteria currently in place.

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The current criteria are not based on objective or empirical forms of measurement, but are based on arbitrary criteria using subjective assessments about the degree of selectivity provided by different MS techniques. The assessments are generally correct, but there are many exceptions, depending on the analyte-matrix pair, the concentration, the MS ions detected, the analytical technique, and the importance of the results.
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The current rates of false negatives are thought to be too high in both types of application (enforcement and non-enforcement) because the identification criteria are too stringent. Furthermore, spurious errors are not typically addressed to reduce false positives, which are best addressed through confirmatory analysis.
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As the word implies, ¡®¡®confirmation¡¯¡¯ requires the results from at least two analyses (which should ideally be orthogonally selective and at least one of them should involve MS detection after an analytical separation), which, in enforcement applications, must agree with each other in terms of analyte identity and concentration.
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4Â¥2009-02-02 23:19:40
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5Â¥2009-02-02 23:21:44
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Originally posted by zxp131415 at 2009-2-2 08:37:
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For non-enforcement purposes, a single analysis using MS detection should be satisfactory, or two analyses using non-MS methods, provided that there has been an empirical demonstration that acceptably low rates of false positives and false negatives occur for the analytes at an adequately low concentration in the targeted matrices. An MS qualitative screening approach may be the best option, followed by a different method to make the confirmation and to improve the quantitative determination.
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We summarize the arguments and the points made in this article in the following proposed sequence for quantitative and qualitative method validation.
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7Â¥2009-02-02 23:45:05
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8Â¥2009-02-02 23:46:00
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Originally posted by qingfeng877680 at 2009-2-2 23:19:
The current criteria are not based on objective or empirical forms of measurement, but are based on arbitrary criteria using subjective assessments about the degree of selectivity provided by diffe ...

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9Â¥2009-02-03 10:23:12
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Originally posted by qingfeng877680 at 2009-2-2 23:45:
For non-enforcement purposes, a single analysis using MS detection should be satisfactory, or two analyses using non-MS methods, provided that there has been an empirical demonstration that accepta ...

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