Estimating limit of detection for mass spectrometric analysis methods
Date
2016-07-01
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Abstract
Avastamispiir (AP) on üks olulisemaid parameetreid analüüsimeetodite valideerimisel. See näitab madalaimat analüüdi kontsentratsiooni, kus võime hea tõenäosusega öelda, et analüüt on tõesti proovis sees. See parameeter on seega oluline tulemuste õigeks tõlgendamiseks ja analüüsimeetodi karakteriseerimiseks. Näiteks võib tuua dopingu ained sportlase veres, narkootilised ained kurjategija uriinis, mürkained toidus, ohtlikud kemikaalid keskkonnas jne. Erinevad standardid, mis avastamispiiri määramist reguleerivad, pole aga omavahel kooskõlas ning seega on tekkinud väga palju erinevaid AP hindamise metoodikaid. Lisaks teevad tihti need metoodikad eeldusi või lihtsustusi, mida pole selgitatud piisavalt viies seega valel kasutamisel ebaadekvaatsete tulemusteni. Esineb ka muid probleeme. Näiteks pole ka piisavalt kirjeldatud avastamispiiri igapäevase kontrollimise korrektseid metoodikaid. Massispektromeetria (MS) on laialt levinud ja hea tundlikkusega analüüsitehnika, mille tõttu on avastamispiir nende puhul eriti oluline. Käesoleva töö käigus võrreldi erinevaid AP hindamise metoodikaid ja uuriti olulisi eksperimendi disaini aspekte kasutades andmeid MS analüüsimeetoditelt. Need tulemused koondati kokku spetsiifiliste soovitustega skeemiks, kus on olulised AP hindamise aspektid välja toodud.
Võtmesõnad: Avastamispiir, valideermine, massispektromeetria, vedelikkromatograafia, paberpihustus ionisatsioon
Limit of detection (LoD) is an important validation parameter for analysis methods. LoD indicates the lowest analyte concentration where it is possible (with good probability) that the analyte signal can be detected. Therefore, it is an important parameter for interpreting analysis results and for characterization of the analytical method (e.g. for detecting illegal doping or drugs from urine, toxic chemicals in food, dangerous chemicals in the environment, etc.). Different standards and guidelines that regulate the estimation of LoD do not correlate with each other and as a result many very different LoD estimation approaches exist. Moreover, often the approaches make assumptions that are not explained leading to inadequate results. Other issues also persist. For example the regular checking of LoD is often not discussed in detail. These problems are especially important in analytical methods that use mass spectrometry (MS) as these are widely used and, due to its high sensitivity, often used for trace analysis. In this work different approaches to estimate LoD were compared and important aspects of experimental design were studied using data collected from MS methods. From these data a comprehensive flowchart was made where all the important aspects of LoD estimation were collected with specific suggestions on estimating LoD. Keywords: Limit of detection, validation, mass spectrometry, liquid chromatography, paper spray ionization
Limit of detection (LoD) is an important validation parameter for analysis methods. LoD indicates the lowest analyte concentration where it is possible (with good probability) that the analyte signal can be detected. Therefore, it is an important parameter for interpreting analysis results and for characterization of the analytical method (e.g. for detecting illegal doping or drugs from urine, toxic chemicals in food, dangerous chemicals in the environment, etc.). Different standards and guidelines that regulate the estimation of LoD do not correlate with each other and as a result many very different LoD estimation approaches exist. Moreover, often the approaches make assumptions that are not explained leading to inadequate results. Other issues also persist. For example the regular checking of LoD is often not discussed in detail. These problems are especially important in analytical methods that use mass spectrometry (MS) as these are widely used and, due to its high sensitivity, often used for trace analysis. In this work different approaches to estimate LoD were compared and important aspects of experimental design were studied using data collected from MS methods. From these data a comprehensive flowchart was made where all the important aspects of LoD estimation were collected with specific suggestions on estimating LoD. Keywords: Limit of detection, validation, mass spectrometry, liquid chromatography, paper spray ionization
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Keywords
massispektromeetria, mõõtmismeetodid, mõõtetäpsus, mass spectrometry, measurement methods, accuracy of measurement