Anal. Chem. 1985, 57,1153-1155
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CORRESPONDENCE An Exceedingly Simple Mass Spectrometer Interface with Application to Reaction Monitoring and Environmental Analysis Sir: Mass spectrometry has proven valuable in the direct analysis of many complex samples, but it is not an established procedure for molecular analysis of aqueous solutions. Two ongoing developments address this problem, the well-known and various forms of liquid chromatography/mass spectrometry (1-7) and semipermeable membrane interfaces (8-15). Several membrane interfaces previously developed to allow introduction of aqueous samples into a mass spectrometer give encouraging results with respect to sensitivity. Shortcomings include reliance on a relatively large sample volume and no provision for the removal of excess or waste solution. In this report, we use the novel concept of flowing the analyte through semipermeable capillary tubing to produce a very simple membrane interface. The work draws upon that of earlier investigators but has the following noteworthy new features: (i) solutions can be recycled through the interface permitting significant opportunity for analysis/control of reacting systems, (ii) utilization with tandem mass spectrometry is demonstrated, and this provides improved detection limits for trace components as well as the ability to monitor, simultaneously, a number of components in a complex mixture, (iii) sample volumes of greater than 1 pL can be analyzed in a batch injection mode, and (iv) the cost of the interface is negligible. EXPERIMENTAL SECTION Corning semipermeable silicon capillary tubing (0.012 in. i.d. X 0.025 in. 0.d.) was employed in all experiments. A 10-pL Hamilton syringe was utilized for direct injection of batch samples into the membrane tubing. Continuous flow through the capillary interface was achieved with a Milton Roy minipump. Experiments employed a Finnigan triple quadrupole mass spectrometer equipped with an Incos data system. Either electron impact (70 eV) or isobutane chemical ionization was used. Argon at a pressure of 2 mtorr (multiple collision conditions) was employed as the collision gas during the tandem mass spectrometry experiments which were carried out at an ion energy of 20 eV. Methylation of cyclohexanone used the reaction conditions described by Johnstone and Rose (16). The experiment employed distilled cyclohexanone and reagent grade potassium hydroxide, methyl iodide, and dimethyl sulfoxide. Twenty milliliters of dimethyl sulfoxide and 9.0 g of potassium hydroxide were stirred for 10 min before the addition of 1.0 mL of cyclohexanone and 5.0 mL of methyl iodide. The reactant vessel was maintained at 40 "C with continuous stirring. The accepted mechanism consists of a-proton abstractionby the strong base followed by methylation at the same position by methyl iodide.
RESULTS AND DISCUSSION Figure 1 illustrates the silicon rubber tube interface to a triple quadrupole for mass spectrometry/mass spectrometry (MS/MS) experiments. A 5-in. length of capillary tubing, fashioned in a loop, is sealed with vacuum epoxy cement into a metal tube such that the U of the loop is isolated from the open ends. When the metal tube is coupled to the liquid inlet system of the mass spectrometer, the lower half of the U enters the vacuum system while access is maintained to the upper half including inlet and outlet arms of the capillary tube. Installation of the interface has no deleterious effect on mass spectrometer performance in terms of base pressure or background.
Table I. Membrane Performance component ether ani1ine 1,3-diphenyl-2-propanone
cyclohexanone dimethyl sulfoxide methyl iodide trichloramine allergy medicine herb phosphorus esters naphthalene toluene acetonitrile naphthol ethyl acetate methyl oleate benzene dimethylnaphthalene dimethylnaphthalene xylenes (mixture of isomers) p-phenylenediamine 1-methylnaphthalene tetralin
solvent water water water water neat MezSO water acetone water acetonitrile acetonitrile neat acetonitrile neat water acetonitrile water EtOH EtOH hair dye ethanol ethanol
A variety of systems have been examined using the interface and some of the results are summarized in Table I. In just a few cases, notably that of chloramine, 1,3-diphenyl-2propanone, and naphthol, the membrane was impermeable to small molecules of moderate polarity. In other cases very low detection limits were obtained M is achieved very readily, in favorable cases detection limits are below lo4 M). The significance of such a simple interface for aqueous and organic solutions lies in its utility not only for a wide range of biological and environmental problems (9) but also for the study of kinetics of organic reactions. The membrane proved to be an excellent interface for the direct monitoring of products from simple organic reactions, as exemplified by the base-catalyzed methylation of cyclohexanone. This was successfully done by first injecting successive small aliquots of the reaction mixture into the membrane and monitoring the molecular ions of the reagent and each of the four methylated products via a MS/MS experiment. Repeated injections into the membrane inlet allowed the mass spectrometer data system to reproduce the kinetic behavior of the reaction. Comparable data were obtained by using either electron impact or chemical ionization. To refine the reaction monitoring system, a single piston pump was connected to the membrane to permit the reacting solution to be continuously scanned and recycled. Allowing a flow rate of 0.25 mL/min, the pump was an effective substitute for manual injections. With this arrangement, as conditions in the reaction vessel were altered, the response could be observed from the MS/MS spectra which were recorded continuously. Additional aliquots of base, methyl iodide, cyclohexanone, and acid were introduced sequentially into the reaction vessel to cause changes in the reaction system. As expected, the changes produced notable effects on the product distribution which could be followed from MS/MS spectra. The addition of extra base
0003-2700/85/0357-1153$01.50/00 1985 American Chemical Society
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ANALYTICAL CHEMISTRY, VOL. 57, NO. 6, MAY 1985
membrane
L+M
Figure 1. Capillary tube membrane used to interface a triple quadrupole mass spectrometer to a reacting organic mixture for continuous in situ monitoring of products, close-up view of the membrane interface.
I
59
MULTIPLE REACTION MONITORING',
I
SELECTION OF 81+ FRAGMENT
R = cyclohexanone + H+
PARENT m/z 99 R
TRIMETHYLCYCLOHEXANONE DAUGHTERS OF 141+
x 13
x6
113 I
W
55
u z a n z 3
81
2 W
->
43
5-I
71
W
123
67
a
141
109
-
-
-
-
Base-catalyzed methylation of cyclohexanone is followed by monitoring reactions (99' 81+, 113' 81', 127' 81+, 141' 81', and 155' 81') Characteristic of the starting material, the mono-, di-, tri-, and tetramethylated products, respectively. Attenuation factors are given for each scan. Figure 2.
I ,
or methyl iodide caused a dramatic increase in the production of methylated cyclohexanones, while the introduction of less than 1equiv of acid aided in the dissolution of the solid base (KOH) and caused a sudden onset of the reaction. This example demonstrates the potential of the interface for exploring reaction parameters in other organic systems. By monitoring the products continuously using multiple reaction monitoring, plots of relative parent ion abundances for the cyclohexanone and each of the methylated products demonstrate the full potential of the interface as an aid for following the time profile of a reacting system (Figure 2). Cyclohexanone protonated by isobutane chemical ionization has a mass to charge ratio of 99. Methylation of cyclohexanone gives a sequence of products having mass to charge ratios that increase by 14 mass units as is expected for the substitution of methyls for hydrogens. These various cyclohexanones each yield characteristic, yet interrelated, fragmentation patterns after undergoing collision activated dissociation (CAD). As an example, each protonated product fragments by losing a molecule of water. This is confirmed by the presence of a daughter ion 18 mass units lower than the parent in the daughter spectrum. Two particular fragment species that are common to all of the cyclohexanones are ions at m / z 55 and 81. The ion a t 81 represents a deprotonated cyclohexene
I
1
I
I
I
111
I
,I
I
Figure 3. Daughter spectrum of m / z 141 in methylation reaction mixture recorded using chemical ionization and the membrane interface.
structure and was chosen as a characteristic fragment for multiple reaction monitoring. Multiple reaction monitoring is a multiscanning experiment in which selected daughter ions formed from preselected parents are sequentially scanned (typically in less than a second). Thus, by comparing the relative intensity of the appropriate ions in the reaction monitoring experiments, an overall time profile of cyclohexanone depletion and formation of methylated compounds is obtained. The rise in the intensity of cyclohexanone probably corresponds to the increase in membrane permeability as heated solution is continuously introduced; the trailing edge of the time profile corresponds to the formation of the various methylated products. The higher methylation products appear later in time, as expected. Any specific methylated product can be examined in depth by closer inspection of the spectrum of daughter ions formed from the parent methylated product. The daughter spectrum of trimethylcyclohexanone (Figure 3) has predominant ions a t mlz 123,81, 59, and 55 among other less abundant ions. Any of these fragment ions can be selected as characteristic fragments that provide a good indication of the progress of formation of trimethylcyclohexanone from cyclohexanone. Ion abundance ratios as well as relative ion intensity confirm the presence of suspected cyclohexanone products during the course of the reaction. Figure 4 illustrates these data. The
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Anal. Chem. 1905. 57. 1155-1157
also open many possibilities including the use of traditional liquid chromatography detectors, including electrochemical detectors, in series with a tandem mass spectrometer to yield simultaneous qualitative and quantitative results. This note has emphasized a sophisticated application of the membrane interface used with a complex mass spectrometer, but it may find most utility when coupled to a simple mass spectrometer for routine environmental analysis.
MULTIPLE REACTION MONITORING' DAUGHTERS OF 141'
-
m .... h
55 81
123
136 blank
I ". I
I ,
.It
,.
XI000
141
a
___-
ACKNOWLEDGMENT We thank L. B. Westover (Dow Chemical) for helpful discussions. Registry No. Cyclohexanone, 108-94-1;methylcyclohexanone, 1331-22-2; dimethylcyclohexanone, 1333-44-4; trimethylcyclohexanone, 50874-76-5; tetramethylcyclohexanone, 95421-59-3. LITERATURE CITED
Flgure 4. Comparison of several dlfferent reactions used to monitor formation of trimethylcyclohexanone in a reacting mixture. R I C is the total ion current (MS scan), 141 is a scan for the selection ion, while 130, 123, 81, and 55 denote reactions of 141 to give these fragment ions.
reaction leading from 141' to 136+ is included as a blank to indicate background signal to noise levels since the parent 141' does not fragment to 136+ after CAD. Furthermore, the ion profiles for each of the selected fragments are smoother than those for the unfragmented parent, as would be expected since reduced noise levels are often observed in MS/MS relative to MS. The RIC (reconstructed ion current) represents the total ion current in the mass spectrum, viz., the sum of all ion signals detected at any particular time. The features of this interface that underline its value and versatility include the simplicity of design, its use with small sample sizes, and its adaptability to virtually any mass spectrometer. Although its response (1-5 min) to changes in sample concentrations was rapid, problems were encountered with memory effects. This may be the result of slow diffusion of some compounds but is alleviated by the disposable nature of the very simple and inexpensive interface. Naturally many compounds do not diffuse through the membrane at all, but this selectivity is key to its operation. The membrane interface seems particularly promising when used in conjunction with a robot-controlled organic reactor or as an industrial process monitor. Rapid product monitoring with the ability for feedback control of reaction conditions to optimize for desired product should be possible. Successful coupling of the membrane to a liquid chromatograph should
Alcock, N. J.; Kuhny, W.; Games, D. E. I n t . J . Mass Spectrom. Ion Phys. 1983, 4 8 , 153-156. McFadden, W. H.; Schwartz, H. J.; Evans, S. J . Chromatogr. 1976, 122,389-396. Takeuchl, T.; Hlrata, Y.; Akumura, Y. Anal. Chem. 1978, 50, 659-660. - -.- - -.
Dark, W. A.; McFadden, W. H.; Bradford, D . J. J . Chromatogr. Sci. 1977. 15. 454-59. McFadden, W. H . J . Chromatogr. Scl. 1980, 18, 97. Liberato, D. J.; Fenselau, C. C.; Vestal, M. L.; Yergey, A. J. Anal. Chem. 1883, 55, 1741-1744. Hayes, M. J.; Tankmayer, E. P.; Vouros, P.; Karger, B. L.; McGuire, J. M. Anal. Chem., 1983, 55, 1745-1752. Weaver, J. C.; Abrams, J. H. Rev. Scl. Instrum. 1979, 50 (4). Westover, L. B.; Tou, J. C.; Mark, J. H. Anal. Chem. 1974, 46 (4), 568. Jones, P. R.; Yang, S. K. Anal. Chem., 1975, 4 7 , 1000. Kallos, G. J.; Mahle, N. H. Anal. Chem. 1983, 55,813-814. Calvo, K. C.; Weisenberger, C. R.; Anderson, L. B.; Klapper, M. H. J . Am. Chem. SOC. 1883, 105,8935-6941. Calvo, K. C.; Weisenberg, C. R.; Anderson, L. B.; Klapper, M. H . Anal. Chem. 1081, 53, 981-985. Weaver, J. C.; Mason, M. K.; Jarrell, J. A,; Peterson, J. W. Blochim. Biophys. Acta 1976, 438, 296-303. Tetler, L. W.; Watson, J. M.; Kirkbright, G. F.; Elliot, M.; Walder, R.; Scrlvens, J. H. Paper presented at the British Mass Spectrometry Society, Fourteenth Meeting, Edinburgh, Sept 16-21, 1984. Johnstone, R. A.; Rose, M. E. Tetrahedron 1979, 35,2169-2173.
Jennifer S . Brodbelt R. Graham Cooks* Department of Chemistry Purdue University West Lafayette, Indiana 47907
RECEIVED for review November 19,1984. Accepted January 22,1985. This work was supported by the National Science Foundation (CHE-8408258).
Simplified Procedure for Forming Polymer-Based Ion-Selective Electrodes Sir: There are a variety of known approaches (1)to prepare polymer-based ion-selective membranes (ISM) and incorporate these membranes into ion-selective electrodes (ISE). All of these procedures for making membranes require a mixture of the polymer, ion-selective reagent, and plasticizer(s), as needed, dissolved in a suitable volatile solvent. The ISM's are then formed by such techniques as casting into a mold and letting the solvent slowly evaporate. An ion-selective electrode can then be made by attaching a piece of the polymer-based membrane to a suitable body or by dip coating
the membrane solution onto a porous substrate (2) or onto a wire (3). We will describe a new simplified procedure for fabricating polymer type ISM's and ISE's. Our process is based on the impregnation of a preformed polymeric electrode body or part with the ion-selective reagent(s). This usually eliminates the need for preparing a separate membrane or a polymeric based membrane solution and then attaching it to an electrode body. In our process the desired ion-selective reagent is dissolved in a liquid which is a swelling agent for the polymer. A
0003-2700/85/0357-1155$01.50/00 1985 American Chemical Society
