Effect of Mobile Phase on Electrospray Ionization Efficiency

Abstract

Electrospray (ESI) ionization efficiencies (IE) of a set of 10 compounds differing by chemical nature, extent of ionization in solution (basicity), and by hydrophobicity (tetrapropylammonium and tetraethylammonium ion, triethylamine, 1-naphthylamine, N,N-dimethylaniline, diphenylphthalate, dimethylphtahalate, piperidine, pyrrolidine, pyridine) have been measured in seven mobile phases (three acetonitrile percentages 20%, 50%, and 80%, and three different pH-adjusting additives, 0.1% formic acid, 1 mM ammonia, pH 5.0 buffer combination) using the relative measurement method. MS parameters were optimized separately for each ion. The resulting relative IE data were converted into comparable logIE values by anchoring them to the logIE of tetrapropylammonium ion taking into account the differences of ionization in different solvents and thereby making the logIE values of the compounds comparable across solvents. The following conclusions were made from analysis of the data. The compounds with pK(a) values in the range of the solution pH values displayed higher IE at lower pH. The sensitivity of IE towards pH depends on hydrophobicity being very strong with pyridine, weaker with N,N-dimethylaniline, and weakest with 1-naphthylamine. IEs of tetraalkylammonium ions and triethylamine were expectedly insensitive towards solution pH. Surprisingly high IEs of phthalate esters were observed. The differences in solutions with different acetonitrile content and similar pH were smaller compared with the pH effects. These results highlight the importance of hydrophobicity in electrospray and demonstrate that high hydrophobicity can sometimes successfully compensate for low basicity.

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.…”

“…The mass analyzers used most for electrospray ionization mechanism studies are ion-trap [3,4,[7][8][9][10] and triple quadrupole [2,6,19,20]. Only in few cases, direct comparison of the obtained results is possible because in most cases the studied compounds and solvent systems differ.…”

“…In previous studies, the ion optics parameters (via optimizing the target mass) of the XCT instrument were optimized and scales with optimized and default ion optics parameters were compared [7,10]. The optimized ion optics parameters improve the consistency in the scale and between the scales.…”

“…In the case of Agilent 6495 Triple Quadrupole, cysteine was used instead of pyridine. The ion trap MS is chosen as reference point for this study because an extensive ionization efficiency scale study for both positive [7] and negative [8] ionization mode have been compiled with this instrument and the reliability of these scales has been demonstrated [10]. These three analytes were chosen to obtain an interpolative prediction model; tetrapropylammonium is the highest responder, pyridine is the low responder, and N,Ndimethylaniline is situated in the middle of the scale measured on the ion trap instrument.…”

MECHANISTIC STUDY OF COLCHICINE’s ELECTROCHEMICAL OXIDATION

“…Since different molecules (i.e. Col's oxidation products) have vastly differing ionization efficiencies in the ESI source, and the influence of pH over their ionization efficiencies strongly depends on their corresponding hydrophobicities [48], it is difficult to follow the pH dependence of Col's electrochemical oxidation by mass spectrometry, simply by comparing the Fig. 3.…”