Standard substance free quantification for LC/ESI/MS analysis based on the predicted ionization efficiencies
Date
2019-07-05
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Abstract
Kõrgefektiivne vedelik kromatograafia elektropihustus massispektromeetria (LC/ESI/MS) on laialt kasutatud väga võimekas analüüsimeetod. Antud meetod on levinud orgaaniliste ühendite, eriti jälgedes, määramise meetod. Kahjuks on sellel meetodil üks puudus. Kõrgefektiivse vedelikkromatograafi ja massispektromeetri ühendamiseks kasutatava elektropihustuse ionisatsiooniefektiivsus on ühendist sõltuv ja võib erineda üle 10 miljoni korra. Ionisatsiooniefektiivsus on defineeritud lahuses olevate analüüdi molekulidest või ioonidest genereeritud gaasifaasiliste ioonide määrana. Seepärast tuleb LC/ES/MS kvantitatiivseks kasutamiseks kasutada standardaineid. Kahjuks ei pruugi standardained kättesaadavad olla, kui tegemist on uudse avastusega, antud ühendeid on raske eraldada või nad on ebastabiilsed.
Minu doktoritöö eesmärgiks on arendada arvutuslik meetod elektropihustuse ionisatsiooniefektiivsuste ennustamiseks, et võimaldada standardainete vaba kvantitatiivset suunamata LC/ESI/MS analüüsi.
Standardainete vaba kvantiseerimise võimaldamiseks uurisin aine struktuuri mõju ionisatsiooniefektiivsusele. Lisaks uurisin analüüsiks kasutatud eluendi mõju ionisatsiooni efektiivsusele. Oma doktoritöö raames näitasin, et mõõdetud ionisatsiooniefektiivsused ning nende trendid erinevate ainete klassides ja erinevates analüüsiks kasutatud eluentides on erinevate instrumentide ülesed. Lõpuks töötasin välja ionisatsiooniefektiivsuse ennustamise mudeli ning meetodi, mis võimldab standardainete vaba kvantiseerimist LC/ESI/MS analüüsil
Liquid chromatography electrospray ionization mass spectrometry (LC/ESI/MS) is a widely applied analytical technique. Furthermore, it is more and more applied in non-target analysis enabling to obtain a more complete picture of biological and chemical processes occurring in living organisms and environment. Standard substances are needed to obtain quantitative information from LC/ESI/MS analysis. The ultimate aim of my doctoral thesis is to provide a solution to overcome the need of standard substances and to quantify compounds detected and identified with LC/ESI/MS. I propose an approach of estimating the concentration of detected and identified compounds in LC/ESI/MS analysis using predicted electrospray ionization efficiencies and using the ionization efficiency to convert LC/ESI/MS signals to the concentrations of compounds. To achieve this, I studied the influence of compound structure to ionization efficiency on a large set of compounds. Furthermore, I studied the effect of chromatographic eluent to ionization efficiency covering most widely used organic modifiers, additives and pH. Thirdly, the effect of instrumentation on ionization efficiency was studied and finally the model was developed. Moreover, I developed an approach named shortly Quantem to provide standard substance free quantification in LC/ESI/MS analysis that accounts for specific sample (analytes and matrix) and specific method (eluents used, gradient program and instrumentation). The developed Quantem approach is made available as a software to LC/ESI/MS community.
Liquid chromatography electrospray ionization mass spectrometry (LC/ESI/MS) is a widely applied analytical technique. Furthermore, it is more and more applied in non-target analysis enabling to obtain a more complete picture of biological and chemical processes occurring in living organisms and environment. Standard substances are needed to obtain quantitative information from LC/ESI/MS analysis. The ultimate aim of my doctoral thesis is to provide a solution to overcome the need of standard substances and to quantify compounds detected and identified with LC/ESI/MS. I propose an approach of estimating the concentration of detected and identified compounds in LC/ESI/MS analysis using predicted electrospray ionization efficiencies and using the ionization efficiency to convert LC/ESI/MS signals to the concentrations of compounds. To achieve this, I studied the influence of compound structure to ionization efficiency on a large set of compounds. Furthermore, I studied the effect of chromatographic eluent to ionization efficiency covering most widely used organic modifiers, additives and pH. Thirdly, the effect of instrumentation on ionization efficiency was studied and finally the model was developed. Moreover, I developed an approach named shortly Quantem to provide standard substance free quantification in LC/ESI/MS analysis that accounts for specific sample (analytes and matrix) and specific method (eluents used, gradient program and instrumentation). The developed Quantem approach is made available as a software to LC/ESI/MS community.
Description
Väitekirja elektrooniline versioon ei sisalda publikatsioone
Keywords
massispektromeetria, elektropihustus-ionisatsioon, ionisatsiooniefektiivsus