Electrochemistry : Thin-Layer Multiple

Daryl A. Roston Chemistry Department Northern Illinois University Dekalb, III.

Instrumentation

Ronald E. Shoup Research Laboratories Bioanalytical Systems, Inc. West Lafayette, Ind.

Peter T. Kissinger Chemistry Department Purdue University and Bioanalytical Systems Inc. West Lafayette, Ind.

Liquid Chromatography/Electrochemistry : Thin-Layer Multiple Electrode Detection Since 1972, over 600 reports concerning the development or utilization of liquid chromatography/electrochemistry (LCEC) have been published (1 ). This rapid increase in the use of LCEC during the past decade attests to the capabilities of the technique. It has been used effectively to address problems in areas as diverse as drug metabolism, forensic chemistry, food science, and neurochemistry. An approach to electrochemical detection that is currently the focus of growing interest is the simultaneous use of two or more working electrodes in LCEC, rather than only one. Dualelectrode detection can be used to improve selectivity, detection limits, and peak identification. It can also extend the accessible potential range of an electrochemical detector. Multipleelectrode detection in a variety of formats will help sustain the growth in LCEC applications during the next several years. The purpose of this article is to provide an introduction to dual-electrode detection for liquid chromatography. Dual-electrode instrumentation and detector cell design considerations are briefly described, with additional emphasis on the improvements that can be manifested by using two detectors instead of one. Due to space limitations, the thinlayer approach will be emphasized. There are, of course, many other possibilities, a few of which have been published (1). 0003-2700/82/A351-1417$01.00.0 © 1982 American Chemical Society

Figure 1. Circuitry for dual-electrode amperometric detection Vi and V 2 are the output voltages for the two working electrodes, W^ and W 2 , held at —E, and —E 2 vs. Ret, the reference electrode. OA = operational amplifier, R = resistor, I — current, Aux = auxiliary electrode

ANALYTICAL CHEMISTRY, VOL. 54, NO. 13, NOVEMBER 1982 · 1417 A

Ref

Single

Dual, Parallel

Dual, Series

w Aux Figure 2. Options for a thin-layer amperometric detector: single, paralleladjacent, and series configuration The stainless steel auxiliary electrode (Aux) is the entire top half of the cube. Ref = reference electrode, W = working electrode

Instrumentation Electronics for Dual-Electrode Detection. Instrumentation required for implementing amperometric or voltammetric experiments simultaneously at different electrodes has been used by electrochemists for years. Dual-electrode "potentiostats" have been developed for use with rotating ring-disk systems (2) and twinelectrode thin-layer cells (3). Two reports have described circuitry for a dual-electrode potentiostat specifically designed for liquid chromatographic dual-electrode detection (4, 5). The principles of dual-electrode potentiostat operation can be understood by considering the circuit shown in Figure 1. The difference in potential between the solution and the working electrode dictates the chemistry that occurs at the working-electrode surface. For single-electrode operation, solution potential control is achieved with a feedback system consisting of an operational amplifier voltage follower (OA-1), the reference electrode, and the auxiliary electrode. The reference electrode "monitors" the difference in potential between the input voltage of OA-1 and the solution. The difference is adjusted to zero by OA-1 by changing the solution potential with the auxiliary electrode. Since Wi is held at virtual ground, the potential of Wi with respect to the reference electrode is —E\.

For dual-electrode detection, the problem is that of controlling the potential at the solution-surface interface of a second working electrode (W2). Nothing can be done to incorporate an independent second working electrode if this action would change the potential of the bulk solution. Otherwise the interfacial potential of the first working electrode would be changed. The recourse is to vary the interfacial potential difference of the second electrode by changing its potential external to the electrochemical cell. If the external potential of W2 is at the potential of the circuit common, then it would necessarily have the same interfacial potential as Wi, since the bulk solution potential would also be the same for both electrodes. The solution is to float the circuit common for the second current-to-voltage converter (OA-3) to a potential which is the difference between the desired electrode potentials for Wi and W2. W2 is now held at E\ — E2, so its potential with respect to the reference electrode is —E2. Obviously, a great deal more is involved in producing a practical device than is depicted in Figure 1. Factors such as time constants, background currents, and offset circuits have to be

considered. Some details are available in previously published reports (2-5). Cell Design Considerations for Dual-Electrode Detection. Many of the considerations involved in designing a dual-electrode detector are the same as those involved in designing a single-electrode detector. Fundamental aspects of electrochemical cell design have been discussed in several recent reviews (6-9). Minimizing cell impedance is important for singleelectrode detection; however, problems arising from high impedance can be particularly acute for dual-electrode operation. In dual-electrode detection, a current response at one electrode causes an iR drop, which results in a change of the solution potential and affects the potentials of both electrode-solution interfaces. This resulting "cross-talk" can render dualelectrode detection impossible to use if the uncompensated resistance (R) is too large. Cross-talk problems can be minimized by positioning the auxiliary electrode as close as possible to the working electrodes, minimizing cell impedance. For multiple electrodes in a thin-layer cell, this may be achieved by placing the auxiliary electrode directly across the thin layer from the working electrodes.

Figure 3. Cyclic voltammogram for caffeic acid Conditions: media, w a t e r - m e t h a n o l - p r o p a n o l - a c e t i c acid (40:4:1:1), 0.018 M ammonium acetate; scan-rate, 100 m V / s ; glassy carbon electrode (GCE). Reprinted from Reference 13

1418 A · ANALYTICAL CHEMISTRY, VOL. 54, NO. 13, NOVEMBER 1982

The basis of the popularity of thinlayer amperometry lies in the adapt ability of the thin-layer detector cell for many different types of analytical tasks. One dual-electrode thin-layer amperometric detector is shown in Figure 2. The parameters responsible for the excellent performance charac teristics of a single-electrode thinlayer amperometric cell are not al tered by introducing the second detec tor electrode in the thin layer. By sim ply changing or rotating the bottom half of the thin-layer cell, it is possible to use a single electrode or dual elec trodes in the parallel-adjacent or se ries orientations (Figure 2). A wide va riety of electrode materials have been utilized in this design, including glassy carbon, carbon paste, platinum, gold, nickel, and mercury-gold amalgam. By changing the working electrode size and shape an enormous number of possibilities exist. Detection Improvements with DualElectrode Detection Series Dual-Electrode Detection. The majority of dual-electrode detec tion publications have dealt with se ries detection (note Figure 2) (10-20). With series detection the eluant is modified by the upstream detector so that a more useful chromatogram can be recorded at the downstream detec tor. Several approaches to series de tection have been reported. Schieffer utilized a series coulometric-amperometric detector to improve selectivity. Interfering compounds that were more easily oxidized than the compounds of interest were removed with the up stream coulometric cell (10,11). An early use of series dual-electrode de tection was reported by King and Kissinger (12). By adding B r - to the aqueous mobile phase, the upstream detector could be used for the con stant current generation of bromine. Use of a reaction coil between the up stream and downstream detector al lowed the generated bromine to react with eluting analytes, such as unsatu rated fatty acids and prostaglandins. The corresponding decrease in the bromine level resulted in a decrease in current at the downstream electrode where the back-reduction of unreacted bromine to bromide was amperometrically monitored. Most series dual-electrode detection work has involved the use of two am perometric detectors positioned in se ries in a conventional thin-layer cell (13-17,19, 20). Series thin-layer am perometric detection can be more clearly understood by considering the cyclic voltammogram of caffeic acid shown in Figure 3. Well-defined oxi dation and reduction currents are evi dent because the oxidized and reduced forms of caffeic acid are stable. Figure

(min)

(min)

Figure 4. Series dual-electrode chromatograms for caffeic acid Conditions: glassy carbon detector potentials, (a) W, = +1.0 V, W2 = +1.0 V, (b) W1 = + 1 . 0 V , W 2 = 0.0 V; 25-cm Biophase C-ιβ column; flow rate = 1 mL/min; mobile phase, water-methanol-propanolacetic acid (40:4:1:1), 0.018 M ammonium acetate. Detector dimensions: dual circular GCE detectors, 3-mm diameter; electrode spacing 0.1 mm; thin-layer channel cross-section dimensions, 0.013 cm X 0.5 mm. Reprinted from Reference 13

4a depicts the series chromatogram for caffeic acid when both electrodes are poised at +1.0 V. Oxidative responses are observed at the upstream (Wx) and downstream (W2) electrodes. The response of the downstream electrode is smaller because of the depletion of caffeic acid at the upstream electrode. Figure 4b shows the series chromato grams resulting when the downstream electrode potential was changed to 0.00 V. An oxidative response was ob served at Wi and a reductive current was observed at W 2 . The reductive current at W 2 corresponds to the re duction of the oxidized form of caffeic acid produced at Wi. Improvements resulting from series amperometric detection are a function of the downstream/upstream peak current ratio, the collection efficiency (13,14): Collection efficiency =

^downstream ^upstream

Because the collection efficiency is a complex function of several parame ters, a range of collection efficiencies is often observed for compounds in a given sample. Maximum collection achievable with a given detector is de termined by critical cell dimensions, namely, the distance between the elec trodes and the ratio of the lengths of the electrodes along the flow-axis (21-23). Less than maximum collec tion is usually the result of chemical


reactions (such as hydrolysis or oxida tive coupling) of the upstream detec tor product that render the product electroinactive at the downstream de tector potential; however, numerous additional factors can decrease collec tion (13). Maximum values for series detectors comprised of equal-surfacearea planar electrodes in a thin-layer cell range from 37% to 42% (13-16, 22). Also, Roston and Kissinger re ported collection values ranging from 3% to 37% for a series of monocyclic phenolic acids separated by reversedphase chromatography (13). If the electrode surface areas are different, then the collection values will reflect this. In the limit, for large surface areas, the collection value will ap proach 100% for chemically reversible redox couples. Several aspects of electrochemical detection can be improved with series amperometric detection. Selectivity can be improved for compounds which have collection values that are signifi cantly higher than coeluting com pounds. Because of differences in col lection, the relative responses of elut ing compounds change, with the re sponses of "high" collection com pounds becoming more dominant. Im provements in selectivity achieved with series amperometric detection are illustrated by Figure 5, which shows simultaneous series detector chromatograms of ethylacetate ex tracts of a commercial beer sample. In

Figure 5. Series dual-electrode chromatograms of an ethylacetate extract of a commercial beer sample Conditions: GCE detector potentials, W, = +0.95 V, W2 = +0.25 V; 25-cm Biophase C18 column; flow rate = 1 mL/min; mobile phase, water-methanol-propanol-acetic acid (40:4:1:1), 0.036 M ammonium acetate. Detector dimensions are detailed in the legend for Figure 4

(a)

(b)

contrast to the upstream-oxidative chromatogram, the dominant downstream-reductive signals are those of vanillic and ferulic acid, compounds that contribute to the flavor and aroma of beer (24, 25). Collection values for vanillic and ferulic acid compounds are higher than those of coeluting species. The utility of the early eluting portion of chromatograms is also enhanced with downstream detection. Series amperometric detection can also be employed to obtain fairly explicit current-potential information for trace quantities of eluting compounds (13). With single electrode detection, only oxidative or reductive current-potential information is obtainable, depending on the state of the eluting species. Using series detection, the oxidized form of a reduced eluate can be produced at the upstream electrode and detected in a reductive mode at the downstream detector. By using incremental detector potential changes, anodic and cathodic currentpotential curves can be generated. Also, after the oxidized form of the reduced eluate is produced and both forms of the compound are present, the polarity of the downstream current is potential dependent. Figure 6 shows three sets of series detection chromatograms observed for four phenolic compounds. The upstream detector potential was + 1.10 V, while the downstream detector potential was changed from

(c)

Figure 6. Series dual-electrode chromatograms for four phenolic compounds 1) 0.04 nmol 4-hydroxybenzoic acid, 2) 0.02 nmol vanillic acid, 3) 0.007 nmol caffeic acid, 4) 0.05 nmol 4-methylcatechol. Conditions: GCE detector potentials (a) W, = +1.1 V, W2 = +0.95 V, (b) W, = +1.1 V, W2 = 0.35 V, (c) W, = +1.1 V, W2 = 0.0 V; 25-cm Biophase C18 column; flow rate = 1 mL/min; mobile phase, water-methanol-propanol-acetic acid (40:4:1:1), 0.036 M ammonium acetate. Detector dimensions are detailed in the legend for Figure 4. Reprinted from Reference 13 1424 A · ANALYTICAL CHEMISTRY, VOL. 54, NO. 13, NOVEMBER 1982

(a)

(b) NE EPI DOPAC DA 5 HIAA HVA 5 HT

0.46 0.45 0.80 0.74 0.98 0.04 0.97

(c)

(d)

(min)

(min)

Figure 7. Simultaneous parallel-adjacent, dual-electrode chromatograms ( 19) of a standard mixture (c) and brain tissue homogenate (d) The peak height ratios (/65o/'eoo) are listed between the dual chromatograms of standards (a) and (b). Conditions: dual glassy carbon electrodes at +650 mV and +800 mV vs. Ag/AgCI; Biophase ODS 5-μηη column (250 Χ 4.6 mm); mobile phase, 1.9 parts THF, 3.5 parts CH3CN, and 96.5 parts 0.15 M monochloroacetate buffer, pH 3.0, containing 200 mg/L sodium octyl sulfate and 0.25 g/L Na2EDTA; flow rate, 1.5 mL/min. Abbreviations: NE, norepinephrine; EPI, epi nephrine; DOPAC, 3,4-dihydroxyphenylacetic acid; DA, dopamine; 5-HIAA, 5-hydroxyindole-3-acetic acid; HVA, homovanillic acid; and 5-HT, serotonin. Reprint ed from Reference 19 by permission of Elsevier Scientific Publishing Company

+0.95 V to +0.35 V to 0.00 V. In this potential range, the downstream re sponse for the compounds changed from oxidative to reductive. At the in termediate downstream potential of +0.35 V, oxidative and reductive re sponses were recorded at the down stream detector. The potential-depen dence of the polarity of the down stream current can be exploited to perform virtual identification of sam ple components. In this sense, the two-stage process is analogous to fluo rescence detection; here the down stream potential, rather than the emission filter, is adjusted to provide selectivity and qualitative peak infor mation. The polarities and relative magnitudes of current responses of standards and unknowns can be com pared at both electrodes to further confirm or negate a preliminary iden tity assignment. This approach has been exploited by Roston and Kissin ger for confirmation of the identity of acetaminophen in a urine sample (13). Recent work by Mayer and Shoup has also pointed out the need to compare collection efficiencies between stan dards and complex samples. In a dualelectrode LCEC method for biogenic amines and metabolites in crude brain

(a)

(b)

(min) Figure 8. Chromatograms of a urine sample obtained 4 h after normal acetamino phen dosage (two Tylenol tablets) Conditions: urine diluted 1:500; parallel-adjacent detector; GCE detector potentials, (a) = +1000 mV (vs. Ag/AgCI réf.), (b) = +650 mV; 25-cm Biophase C18 column; flow rate = 1.0 mL/min; mobile phase, 0.1 M acetate buffer (pH 4): methanol, 33:1


DA NE EPI

DOPAC

5HIAA

5 HT HVA

+ E(V)

Figure 9. Hydrodynamic voltammograms ( 19) 19) for foraaseries seriesofof biogenic biogenicamines aminesand and metabolites obtained under the conditions of Figure 7 Abbreviations are defined in Figure 7

homogenate (19), qualitative peak identification based on three dimensions—retention time, electrochemical reactivity, and dual-electrode collection efficiency—demonstrated that an apparently pure upstream peak was actually composed of two electroactive brain metabolites. Downstream, only the metabolite of interest was detectable. Several studies have demonstrated that series amperometric detection can extend the accessible potential range of electrochemical detection (13, 14, 20). An inherent problem associated with detection at high potentials (>+1.0 V or < - 1 . 0 V) is the high background current due to the oxidation or reduction of water, oxygen, hydronium ion, and other mobile-phase constituents. When the presence of trace quantities of analyte requires the use of high gains and the magnitude of baseline drift is comparable to the signal, obtaining usable chromatograms becomes a difficult task. In addition, use of graphite electrodes at extreme potentials often results in rapid decay of performance. If the compound of interest has significant collection, downstream detection at lower potentials minimizes problems associated with baseline drift.

While most series electrode detectors are used to reduce the chromatogram's complexity downstream, it is also possible to use the upstream electrode as a "generator" electrode to increase the downstream peak content. In essence, it acts as a very low deadvolume postcolumn reactor. In a sample containing both forms of a redox couple, for example, the upstream electrode may be used to convert O, the oxidized form, to R and then detect R (either as present in the original sample or electrogenerated) downstream for quantitation. Using this concept, Allison and Shoup (20) reported a novel simultaneous thin-layer assay for thiols and disulfides. Twin mercury amalgam electrodes in series first converted disulfides to the thiol form at —1.1 V and then detected all thiols at +0.15 V downstream. Without series detection, the direct determination of the disulfide would be intractable, due to excessive background current. While conceptually similar to the design of Eggli and Asper (18), the thin-layer version affords the ability to monitor high-efficiency, high-speed separations without significantly contributing to the peak variance. Parallel-Adjacent Dual-Electrode Detection. The parallel-adja-


cent arrangement (Figure 2) can provide qualitative estimates of peak purity through the generation of current ratios (25-28). It is also capable of simultaneously profiling oxidizable and reducible solutes in one injection. This mode is analogous to dual wavelength UV absorbance detection, where simultaneous chromatograms at the two wavelengths as well as the real-time absorbance ratios are provided. Whereas a UV-VIS spectrum is usually taken prior to optical detection, in LCEC the compounds to be determined are first characterized by cyclic voltammetry or hydrodynamic voltammetry (HDV). The current-potential curve is used to discern the appropriate detector potential for LCEC determinations, and comparison of the current-potential curves of sample constituents and standards is frequently used to confirm identity assignments. HDVs are obtained by performing a series of LCEC experiments during which the detector potential is incrementally changed, a procedure that is laborious, time-consuming, and rarely done for more than a few samples. With simultaneous dual potential monitoring, every injection provides an instantaneous two-point hydrodynamic voltammogram, which is sufficient for most studies. Shoup and Mayer utilized this approach to prove peak identities for phenols in industrial wastewater (27), various neurochemicals (Figure 7) in brain (19), and plasma (28). It is interesting to note the sensitivity of these ratios to substituents. For example, even though norepinephrine (NE), epinephrine (EPI), dopamine (DA) and 3,4-dihydroxyphenylacetic acid (DOPAC) are all catechols, their ratios cluster into two groups, depending on whether a /3-hydroxy group on the sidechain is present (ratio = 0.45, NE and EPI) or not (ratio » 0.75, DOPAC and DA). Roston and Kissinger utilized current ratios obtained with parallel-adjacent detection to confirm the identity of benzene metabolites in vitro (26). Parallel-adjacent amperometric detection can also render simultaneous determinations of several components more feasible. Frequently, it is desirable to determine two or more compounds in the same chromatogram. The detector potential has to be sufficiently positive (for oxidative detection) to oxidize all of the compounds of interest. Therefore, it is often necessary to use higher potentials (>1.0 V vs. Ag/AgCl) whenever simultaneous determinations are desired. Often, the complexity of the chromatogram resulting at the higher detector potential obscures the amperometric response for one or more of the compound^) of interest. If the chromato-

800 mV

700 mV

800 mV-700 mV

(min) Figure 10. Three chromatograms of brain homogenate biogenic amines obtained simultaneously using parallel-adjacent electrodes at + 8 0 0 mV and + 7 0 0 mV The third tracing is the difference output. Conditions: See Figure 7

CH3CN Gradient Profile

+ 0.98 V

Time (min) Figure 11. Simultaneous oxidation and reduction chromatograms of priority pollu tant phenols using parallel-adjacent glassy carbon electrodes at —0.75 V and + 0 . 9 8 V vs. Ag/AgCI Peak identification: 1, phenol; 2, 2,4-dinitrophenol; 3, p-nitrorhenol, 4, o c h l o r o p h e n o l ; 5, 4,6-dinitro-ocresol; 6, 2,4-dimethylphenol; 7, 4-chloro-3-methylphenol; L, o-nitrophenol; 9, 2,4-dichlorophenol; 10, 2,4,6-trichlorophenol; 1 1 , pentachlorophenol. Conditions: linear gradient from 3 0 % C H 3 C N / 7 0 % 0.05 M NaCIC-4, 0.005 M citrate pH 3.8 to 5 0 % / 5 0 % over 15 min, then to 8 0 % C H 3 C N / 2 0 % buffer at 20 min. Flow rate: 2 m L / m i n . Column: Biophase ODS 5 μ η ι (250 Χ 4.6 mm)


graphic peak of a more easily oxidized (reduced) compound is obscured in the high-potential chromatogram, dual-potential monitoring can en hance the feasibility of performing the assay. High- and low-detector-poten tial chromatograms can be obtained simultaneously. The high-potential chromatogram can be used to monitor the compounds that are more difficult to oxidize (or reduce). During the same experiment, the less complex low-potential chromatogram is used to monitor the more easily oxidized analyte(s), often with lower detection limits. Increased utility resulting from dual-potential monitoring with paral lel-adjacent detection is shown in Fig ure 8, which shows chromatograms of a urine sample obtained 4 h after nor mal Tylenol (acetaminophen) dosage. Most of the major peaks in the chro matogram are acetaminophen metab olites. Urinary metabolites of acetami nophen differ widely in oxidation po tential, and the more easily oxidized compounds are present at the lowest concentrations. It is a principle of aro matic drug metabolism that the more thoroughly metabolized compounds have the lowest oxidation potentials and can therefore be detected most fa vorably at the lower potential elec trode. Simultaneous operation at two potentials improves the ability to ob tain qualitative and quantitative in formation about eluting peaks. An additional application of the parallel-adjacent configuration in volves the use of the amperometric de tectors in a differential mode to en hance specificity. To implement dif ferential mode detection, the detec tors are poised at potentials encom passing the region where the current response of the compound is markedly dependent on detector potential. Specificity results when the response of the electrode poised at the base of the electroactive region (Wi) is elec tronically subtracted from the re sponse of the electrode poised on the diffusion plateau (W2). For example, an enhanced response for the dopa mine metabolite, homovanillic acid (HVA), over more easily oxidized compounds can be realized by operat ing parallel-adjacent electrodes along the rising portion of HVA's hydrodynamic voltammogram (Figure 9). In Figure 10, chromatograms at +800 mV, +700 mV, and 800-700 mV are shown. The peaks for serotonin and 5-HIAA are diminished relative to HVA. Because the differential output is recorded, only compounds display ing a significant current change be tween the detector potentials produce signals. Parallel-adjacent differential mode detection offers the possibility for significant enhancement in detec-

w2 R

O

R

O

R

O

R

O

R

O

R

O

Wi

Figure 12. Redox cycling using parallel-opposed dual electrodes

tor selectivity for any electroactive compound. It also offers the possibili ty of minimizing the contribution of baseline noise and thereby extending detection limits. Another interesting parallel-adja cent option is to maintain one elec trode at a fairly high oxidizing poten tial and one at a reducing potential (28). In Figure 11, the ability to detect all of the EPA-designated priority pol lutant phenols in one injection by si multaneously obtained red/ox tracings is demonstrated. The upper recording at —0.75 V is due to the four phenols that contain a reducible nitrophenol moiety. At +0.98 V all of the oxidizable phenols are profiled. Parallel-Opposed Dual-Elec trode Detection. Parallel-opposed dual-electrode detection can be imple mented by placing two electrodes op posite each other in the thin-layer cell. The auxiliary electrode must be offset. If the oxidized and reduced forms of a compound are stable and the elec trodes are poised at the appropriate potentials, the parallel-opposed con figuration can be used to implement redox cycling, depicted in Figure 12. Oxidized molecules from Wi will dif fuse across the eluant stream to W2, where they are reduced. The reduced species is then available for reoxidation at Wi. Thus, the parallel-opposed configuration affords the capability for amplifying the signal for com pounds amenable to redox cycling. The magnitude of the enhancement is dependent on several parameters, in cluding the length of the electrode along the flow axis, the distance be tween the electrodes, and the linear (cm/s) mobile phase velocity. It is like ly that application of detector cells of this type will be significant only for microcolumn liquid chromatography where the low volume flow rate will make redox cycling easier to achieve. An attempt at using a parallel-op posed dual-electrode detector to en hance the signal of catecholamines was unsuccessful because the flow rate was too high to allow redox cycling to

occur within the thin layer (29). It should be acknowledged that the ad vantages of redox cycling in thin-layer cells were first recognized and demon strated by Reilley and co-workers (al beit for a stationary solution) (30). References (1) Shoup, R. E., Ed. "Recent Reports on Liquid Chromatography/Electrochemis try"; BAS Press: West Lafayette, Ind., 1982 (2) Napp, D. T.; Johnson, D. C ; Bruckenstein, S. Anal. Chem. 1967, 39, 481. (3) Anderson, L. B.; Reilley, C. N. J. Electroanal. Chem. 1976, 39, 538. (4) McClintock, S. Α.; Purdy, W. C. Anal. Lett. 1981,14, 791-98. (5) Blank, L. J. Chromatogr. 1976,117, 35-46. (6) Weber, S. G.; Purdy, W. C. Anal. Chim. Acta 1978,100, 531-544. (7) Stulik, K.; Pacakova, V. J. Electroanal. Chem. 1981,129,1-24. (8) Kissinger, P. T. Anal. Chem. 1977,49, 447-56 A. (9) Kissinger, P. T.; Bruntlett, C. S.; Bratin, K ; Rice, J. R. "Trace Organic Analy sis: A New Frontier in Analytical Chem istry"; Chesler, S. N.; Hertz, H. S., Eds.; Nat. Bur. Stand. U.S. Spec. Publ. 519, 1979 705-12. (10) Schieffer.G. W. Anal. Chem. 1981, 53, 126-27. (11) Schieffer, G. W. Anal. Chem. 1980, 52,1994-98. (12) King, W. P.; Kissinger, P. T. Clin. Chem. 1980, 26, 1484-91. (13) Roston, D. Α.; Kissinger, P. T. Anal. Chem. 1982,54,429-34. (14) MacCrehan, W. Α.; Durst, R. A. Anal. Chem. 1981,53,1700-1704. (15) Goto, M.; Sakurai, E.; Ishii, D. J. Chromatogr. 1982,238, 357-66. (16) Goto, M.; Nakamura, T.; Ishii, D. J. Chromatogr. 1981, 226, 33-42. (17) Bratin, K.; Kissinger, P. T. J. Liq. Chromatogr. 1981,4,321-57. (18) Eggli, R.; Asper, R. Anal. Chim. Acta 1978,107,253-59. (19) Mayer, G. S.; Shoup, R. E. J. Chroma togr. , in press. (20) Allison, L. Α.; Shoup, R. E., accepted for publication in Anal. Chem. (21) Braun, R. J. Electroanal. Chem. 1968,19, 23-35. (22) Gerischer, H.; Ingeburg, M.; Braun, R. J. Electroanal. Chem. 1965,10, 553-67. (23) Matsuda, H. J. Electroanal. Chem. 1968,16, 153-64. (24) Charalambous, G.; Bruckner, K. J.; Hardwick, W. Α.; Linnebach, A. Tech. Q. Master Brew. Assoc. Amer. 1973,70, 74-78.


(25) Roston, D. Α.; Kissinger, P. T. Anal. Chem. 1981,53,1695-99. (26) Roston, D. Α.; Kissinger, P. T. Anal. Chem. 1982,54,1798-1802. (27) Shoup, R. E.; Mayer, G. S. Anal. Chem. 1982,54,1164-68. (28) Mayer, G. S.; Shoup, R. E., unpub lished data. (29) Fenn, R. J.; Siggia, S.; Curran, D. J. Anal. Chem. 1978,50, 1067-73. (30) Anderson, L. B.; Reilley, C. N. J. Electroanal. Chem. 1965,10, 295-305. Daryl A. Roston is assistant profes sor of chemistry at Northern Illinois University. He recently completed two years as a postdoctoral associate of P. T. Kissinger at Purdue Universi ty. Roston received his Β A in chemis try from the College of Wooster and his PhD in analytical chemistry working with William R. Heineman at the University of Cincinnati in 1980. His research interests focus on novel LCEC techniques and stripping voltammetry. Ronald Shoup is research director at Bioanalytical Systems. He earned undergraduate degrees in mathemat ics and chemistry at Purdue Univer sity and pursued graduate study at Michigan State and, later, Purdue, where he received his PhD in analyti cal chemistry. His current research interests include the use of high speed separations for improved LC analyses, optimizing multiple elec trode detectors to maximize the avail able information content of the chromatogram, and improving signal-tonoise ratios and gradient compensa tion in LCEC. Peter T. Kissinger is president of Bioanalytical Systems and professor of chemistry at Purdue University. He received a BS in chemistry from Union College, Schenectady, New York, and a PhD from the University of North Carolina at Chapel Hill. Kissinger's group pioneered the de velopment of thin-layer LCEC over the past 10 years. His current re search focuses on the chemical mech anism of toxicity for aromatic xenobiotics and further refinement of the LCEC technique.

Electrochemistry : Thin-Layer Multiple

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