Towards the electrospray ionization mass spectrometry ionization efficiency scale of organic compounds

Abstract

An approach that allows setting up under predefined ionization conditions a rugged self-consistent quantitative experimental scale of electrospray ionization (ESI) efficiencies of organic compounds is presented. By ESI ionization efficiency (IE) we mean the efficiency of generating gas-phase ions from analyte molecules or ions in the ESI source. The approach is based on measurement of relative ionization efficiency (RIE) of two compounds (B 1 and B 2 ) by infusing a solution containing both compounds at known concentrations (C 1 and C 2 ) and measuring the mass-spectrometric responses of the protonated forms of the compounds (R 1 and R 2 ). The RIE of B 1 and B 2 is expressed asThe relative way of measurement leads to cancellation of many of the factors affecting IE (ESI source design, voltages in the source and ion transport system, solvent composition, flow rates and temperatures of the nebulizing and drying gases). Using this approach an ESI IE scale containing ten compounds (esters and aromatic amines) and spanning over 4 logRIE units has been compiled. The consistency of the scale (the consistency standard deviation of the scale is s ¼ 0.16 logRIE units) was assured by making measurements using different concentration ratios (at least 6-fold concentration ratio range) of the compounds and by making circular validation measurements (the logRIE of any two compounds was checked by measuring both against a third compound). Copyright # 2008 John Wiley & Sons, Ltd.The electrospray ionization (ESI) method 1,2 is one of the most widely used ionization methods in contemporary mass spectrometry (MS). Its compatibility with liquid chromatography (LC), soft nature and virtual absence of restrictions on the molecular mass of the compounds have enabled its successful application to a vast number of different analytes. 3,4 The ESI method has played a key role in the spectacular success of LCMS during the recent years. Besides practical applications research has been carried out on elucidating the ESI mechanism 5-12 and on the principles that govern the ESI ionization efficiency of different analytes. 6,9 By ESI ionization efficiency we mean the efficiency of generating gas-phase ions from analyte molecules or ions in the ESI source. ESI is not an efficient method for generation of gas-phase ions. Only a small fraction of analyte molecules are ionized in the ion source and only a part of the resulting gas-phase ions are successfully transmitted to the mass analyzer and eventually detected. 7 The actual process of generating gas-phase ions in the ESI source is complex. A multitude of processes in the liquid phase as well as in the gas phase and on the gas-liquid boundary must be considered. Furthermore, solvents, additives and impurities may cause ionization suppression or an enhancement effect 8,11 that is frequently observed when introducing a solution containing different compounds into an ESI source (also known as the matrix effect). Several models for relating the response of an analyte ion in the mass spectrum to the a...

Ionization Efficiency of Doubly Charged Ions Formed from Polyprotic Acids in Electrospray Negative Mode

“…They concluded that analytes need to have a large enough nonpolar area to move to the surface of the droplet and also a structural element that allows charging (protonation, deprotonation, adduct formation, etc.). This tendency was also confirmed by Leito et al [17] based on a study of esters and aromatic amines. Ehrmann et al [21] tried to predict analyte signal in ESI/MS and observed the best predicting power while using the solution phase basicity of analyte (pK b ).…”

“…As the evaluation of absolute IEs is difficult if not impossible, the term relative ionization efficiency (RIE) has been introduced [17] (see Formula 1 in Experimental).…”

Transferability of the Electrospray Ionization Efficiency Scale between Different Instruments

“…The mechanisms of ESI are complex and numerous studies [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15] have been carried out for its elucidation. It has been shown that the electrospray ionization efficiency (IE) [16] of an analyte is influenced by its molecular structure as well as the solvent (including its pH and additives) and the MS system. Despite intense research, the mechanisms of ESI are not fully understood.…”

“…In order to withdraw the influence of the instrument (as well as numerous other influencing factors) a relative measurement approach has been proposed [16], whereby every measurement essentially compares the IE of two compounds simultaneously in the same solution. An extensive IE scale in the positive ion mode has been compiled with this approach [7].…”

“…An extensive IE scale in the positive ion mode has been compiled with this approach [7]. Having two compounds simultaneously in the same solution can lead to asymmetrical mutual suppression of ionization and thereby biased results [16]. In order to avoid this, a different approach-involving separate IE measurements of individual compounds against an external standard compound-has been used for compiling an extensive IE scale in the negative ion mode [8].…”