Correspondence Anal. Chem. 1996, 68, 3493-3497
Mechanism of Signal Suppression by Anionic Surfactants in Capillary Electrophoresis-Electrospray Ionization Mass Spectrometry Kimber L. Rundlett† and Daniel W. Armstrong*
Department of Chemistry, University of MissourisRolla, Rolla, Missouri 65401
Micellar-mediated capillary electrophoresis (CE) is used for a wide variety of applications, including the separation of pharmaceuticals, environmental contaminants, illicit drugs, DNA fragments, and many other biological samples. The electrospray ionization interface is one of the most common CE-MS interfaces. Coupling micellar-mediated CE separations with MS detection combines two very powerful, widely applicable analytical techniques. Some types of surfactants strongly interfere with electrospray ionization mass spectrometric (ESI-MS) detection of analytes, and in many cases the ESI-MS analyte signals are completely quenched. Only a few reports have appeared that describe the ESI-MS detection of analytes in the presence of surfactants; however, the exact mechanism of ionization suppression has not yet been addressed. In this work, a modified aerosol ionic redistribution (AIR) model is presented that qualitatively explains the results of previous studies, including those using “polymeric surfactants”. Analyte ionization suppression by surfactants appears to be caused by Coulombic interaction between oppositely charged solute and surfactant ions in the ESI-produced offspring droplets. It appears that the ability of surfactants to quench electrospray ionization is directly related to the surface activity and the charge of the surfactant. Also, highly surface active components tend to be enriched in ESI-produced offspring droplets. Analyte ion signals can be detected under conditions that lower the surface concentration of oppositely charged surfactant ions in aerosol droplets. The mechanistic information outlined here may be used to design micellarmediated CE separations that allow detection of analyte ions by ESI-MS. Capillary electrophoresis (CE) produces separations of exceptionally high efficiency in a relatively short time and requires very little sample or run buffer. However, like other microscale separation techniques, CE suffers from poor sensitivity. A good deal of effort has been expended on interfacing CE with high†
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sensitivity mass spectrometer (MS) detectors.1-6 One of the most common and powerful CE-MS interfaces is based on electrospray ionization (ESI). Much of the previous work with CE-ESI-MS has concentrated on demonstrating the wide applicability of this technique, especially in areas of protein and peptide separations and analysis1-9 and study of some small molecules.10-12 Other studies have been designed to probe the many aspects of the ESI mechanism that eventually produces gas-phase analyte ions.13-18 ESI-MS has been reviewed in detail by Kebarle and Tang.19 The electrospray ionization process can be described by several steps.19 These are shown in Figure 1. First, charged droplets are produced by the application of high electric fields to a capillary filled with an electrolyte solution. After the droplets are formed at the capillary tip, they are accelerated toward the counter electrode. The solvent evaporates from the droplets until the Rayleigh limit is reached. The Rayleigh limit occurs when the (1) Smith, R. D.; Goodlett, D. R.; Wahl, J. H. In Handbook of Capillary Electrophoresis; Landers, J. P., Ed.; CRC: Boca Raton, FL, 1994; Chapter 8. (2) Tomer, K. B.; Deterding, L. J.; Parker, C. E. Advances in Chromatography, Vol. 35; Marcell Dekker: New York, 1995; Chapter 2. (3) Cai, J.; Heinon, J. J. Chromatogr. A 1995, 703, 667. (4) Niessen, W. M. A.; Tjaden, U. R.; van der Greef, J. J. Chromatogr. 1993, 636, 3. (5) Smith, R. D.; Wahl, J. H.; Goodlett, D. R.; Hofstadler, S. A. Anal. Chem. 1993, 65, 574A. (6) Smith, R. D.; Udseth, H. R. In Capillary Electrophoresis Technology; Guzman, N. A., Ed.; Dekker: New York, 1993. (7) Smith, R. D.; Udseth, H. R.; Barinaga, C. J.; Edmonds, C. G. J. Chromatogr. A 1991, 559, 197. (8) Moseley, M. A.; Jorgenson, J. W.; Shabanowitz, J.; Hunt, D. F.; Tomer, K. B. J. Am. Soc. Mass Spectrom. 1992, 3, 289. (9) Thibault, P.; Paris, C.; Pleasance, S. Rapid Commun. Mass Spectrom. 1989, 18, 844. (10) Olivares, J. A.; Nguyen, N. T.; Yonker, C. R.; Smith, R. D. Anal. Chem. 1987, 59, 1230. (11) Johansson, J. M.; Pavelka, R.; Henion, J. D. J. Chromatogr. A 1991, 559, 515. (12) Perkins, J. R.; Parker, C. E.; Tomer, K. B. J. Am. Soc. Mass Spectrom. 1992, 3, 139. (13) Tang, L.; Kebarle, P. Anal. Chem. 1991, 63, 2709. (14) Gomez, A.; Tang, K. Phys. Fluids 1994, 6, 404. (15) Tang, K.; Gomez, A. Phys. Fluids 1994, 6, 2317. (16) Dole, M.; Mack, L. L.; Hines, R. L.; Mobley, R. C.; Ferguson, L. D.; Alice, M. B. J. Chem. Phys. 1968, 49, 2240. (17) Iribarne, J.; Thompson, B. J. Chem. Phys. 1976, 71, 2287. (18) Taflin, D. C.; Wood, T. L.; Davis, E. J. Langmuir 1989, 5, 376. (19) Kebarle, P.; Tang, L. Anal. Chem. 1993, 65, 972A.
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Figure 1. Schematic representation of the Taylor cone and charged droplet formation during the electrospray process (positive ion mode). High concentrations of highly surface active anionic surfactants may reduce the efficiency of the electrospray process due to the large number of surfactant anions adsorbed at the surface, which could, in turn, affect the Taylor cone. This figure is adapted from ref 19.
Coulombic repulsion of the ions in the droplet is strong enough to overcome the liquid surface tension, causing droplet fission.20 The resulting droplets are significantly smaller and enriched in charge compared to the parent droplets. Although there is some variation with solution conditions, offspring droplets were observed to carry about 2% of the parent mass and 15% of the parent charge.18 Evaporation of solvent from these offspring droplets causes them to shrink until they become unstable and produce even smaller droplets, which are further enriched in charge. Finally, the analyte ions are transferred from the droplets to the gas phase, where secondary gas-phase processes may occur to modify the ions before they are introduced into the MS detector. Two research teams have photographed charged droplets undergoing fission processes.14,15,21 Gomez and Tang took shadowgraphs of parent droplets in the process of Coulombic explosions.14,15 In another study, photographs were taken of droplets undergoing fission in a droplet electrospray mass spectrometry interface.21 From these studies, it appears that charged droplets undergo fission by the same mechanism: the parent droplet becomes elongated, forming a tail-like appendage.14,15,21 Smaller droplets with higher charge-to-mass ratios are then emitted from the tail of the parent droplet. In addition, it appears that species found in the offspring droplets are those that reside on the surface of the parent droplet.14,15,19,22 One of the advantages of CE is the variety of run buffer additives that can be used to control the separations. These include ionic surfactants,23,24 polymers,25-27 and chiral selectors.28,29 However, many of these species are not compatible with either the ESI interface or the mass spectrometer.1-6 High concentrations of nonvolatile ionic compounds reduce the MS signal of (20) Rayleigh, J. W. S. Philos. Mag. 1882, 14, 184. (21) Hager, D. B.; Dovichi, N. J.; Klassen, J.; Kebarle, P. Anal. Chem. 1994, 66, 3944. (22) Abbas, M. A.; Latham, J. J. Fluid Mech. 1967, 30, 663. (23) Terabe, S.; Otsuka, K.; Ando, T. Anal. Chem. 1985, 57, 834. (24) Strasters, J. K.; Khaldi, M. G. Anal. Chem. 1991, 63, 2503. (25) Cohen, A. S.; Terabe, S.; Smith, J. A.; Karger, B. L. Anal. Chem. 1987, 59, 1021. (26) Strege, M.; Lagu, A. Anal. Chem. 1991, 63, 1233. (27) Guttman, A.; Cooke, N. Anal. Chem. 1991, 63, 2038. (28) Ward, T. J. Anal. Chem. 1994, 66, 633A. (29) Vespalec, R.; Boeck, P. Electrophoresis 1994, 15, 755.
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analyte ions, destroying the sensitivity.1-6,13 The best results are obtained with low ionic strength solutions (
