Anal. Chem. 1991, 63, 457-459
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Real-Time Detection of Parts per Trillion Levels of Chemical Warfare Agents in Ambient Air Using Atmospheric Pressure Ionization Tandem Quadrupole Mass Spectrometry S. N. Ketkar,* S. M. Penn, and W. L. Fite Extrel Corporation, 575 Epsilon Drive, Pittsburgh, Pennsylvania 15238
An atmospheric pressure lonlzatlon tandem quadrupole mass spectrometer system was used to detect, In real time, low levels of chemical warfare agents GB and VX In air. The system exhlbits detection llmlts of 7.2 ppt (parts per trllllon) for GB and 6 ppt for VX with a response time of 15 s, using a single reaction monltorlng scheme. I n order to Increase the speclflcity of detection, two parent-todaughter transltlons can be monltored. However, when such a scheme Is utlllzed, the detectlon llmlt for GB Is 14.1 ppt and that for VX Is 100 ppt.
Recent events concerning the chemical plant in Libya alleged to produce chemical warfare agents has brought to the public's attention the horrors associated with the use of such agents. Geneva agreement notwithstanding, there have been allegations of the use of such weapons of mass destruction in different parts of the world. These events have also brought about an effort amongst the superpowers to destroy their stockpile of chemical warfare agents. The above-mentioned events have demonstrated the need for real-time detection, with high specificity, of low levels of chemical agents in air. A recent article in Analytical Chemistry describes the work done in this area using resonant-enhanced multiphoton ionization (REMPI) coupled with a time-of-flight mass spectrometer (I). Use of REMPI provides a highly selective ionization mechanism, thus increasing the specificity of detection. T h e detection limits are still not low enough (about 300 ppt (parts per trillion) for diisopropyl methyl phosphonate); however, with more effort in this field, the detection limits will be lowered. We have been involved, for the past 3 years, in a n effort to develop a mass spectrometer based system for the real-time, sensitive, and specific detection of chemical agents in the effluent of demilitarization furnace stacks (2). This system utilizes atmospheric pressure ionization (API) for sensitive ionization and tandem quadrupole mass spectrometry (MS/MS) for specific detection. T h e nature of the everchanging stack effluent matrix makes such a task very difficult. Although this system achieves the desired sensitivity (tens of parts per trillion), the complex nature of the stack effluent makes it abundantly clear that MS/MS lacks the desired specificity in this application. The results of the work performed on stack sampling will be published later. However, when monitoring for chemical agents in ambient air, MS/MS does indeed achieve the desired specificity so as to avoid false positives. We report here our findings on detecting two nerve agents, GB and VX, in ambient air, a t concentration levels below 20 ppt. EXPERIMENTAL SECTION An Extrel API MS/MS system was used in this work. This system has been described earlier in detail ( 3 ) ,so only a brief overview will be present here. The API source uses a corona discharge, operating at atmospheric pressures, as a means of achieving the primary ionization. Rapid ion molecule reactions
in this high-pressure region produce hydronium ion and its water-clustered ions, H30+and (H30)+.(H20),. These ions can be considered, for all practical purposes, as the primary ions. Proton-transfer reactions between these ions and the analyte, X, are used to produce the protonated molecular ion of the analyte XH+ and its water clustered ions XH+-(H20),. A low-pressure declustering region is used to break up these weakly bound water clustered ions ( 3 , 4 ) . The protonated molecular ion, XH+, is then fragmented in the tandem quadrupole mass spectrometer. Three quadrupoles with 3/,-in.-round and 6-in.-long poles are used in the mass spectrometer. The center quadrupole is used in an radio-frequency (rf) only mode as the collision cell. The collision cell has end plates made of a leaky dielectric material (5) to increase the transmission of this tandem quadrupole mass spectrometer. In normal mode of operation, the first quadrupole is set to transmit the protonated molecular Torr, is used ion of the analyte. Argon, at a pressure of 1 X in the collision cell to fragment this protonated molecular ion. The third quadrupole is used to transmit one or more of the fragmentation products. A counting channel electron multiplier is used, together with a counting preamplifier and a counter/scalar, to detect the ions transmitted by the third quadrupole. Both the first and the third quadrupoles are operated with unit mass resolution. By monitoring more than one fragmentation product, the specificity of this system is increased. Experiments were performed by challenging the inlet of the system with varying amounts of chemical agents in air. A microsyringe pump was used to deliver a weak solution of chemical agent, in hexane, to the inlet tube of the system. The inlet tube of the system was heated, and the chemical agent was vaporized in this tube. The chemical agent vapors were mixed with 1.5 L/min of air that was being drawn from the ambient atmosphere. The concentration of the chemical agent in the atmosphere thus generated was varied by varying the flow rate of the syringe pump. We were able to challenge the system with chemical agent concentrations from 5 to 80 ppt. The system response to the varying concentration of the agent was measured on four consecutive days. The detector was operated in a pulse counting mode, with a dwell time of 5 s. By use of this dwell time, the system response was measured to be about 15 s (3). All the work was performed at Chemical Agent Munitions Disposal System (CAMDS) at Tooele Army Depot, Tooele, UT, where facilities for handling chemical agents are available. GB (Sarin). Chemical agent GB (Sarin) is a nerve agent, isopropoxymethylphohorylfluoride. This presents a vapor hazard because of its relatively high vapor pressure (2.9 Torr at 25 " C ) (6). At the time this work started, little information about relevant properties such as electron affinity, proton affinity, etc., was known. We performed bracketing experiments to determine the proton affinity of GB. The results of our experiments indicate that GB has a proton affinity of about 210 kcal/mol (2). This rather high proton affinity makes it a good candidate for ionization when using API. The rather high proton affinity also makes it unlikely that other compounds occurring in ambient air will quench the proton-transfer reaction between hydronium ion and GB. Figure 1shows the fragmentation pathway for the protonated molecular ion of GB. The major fragment for GBH' (m/z = 141) is m / z = 99. The system monitors the transition m / z = 141 --c 99 for the detection of chemical agent GB. VX. Chemical agent VX is a nerve agent, 0-ethyl S-[2-(diisopropylamino)ethyl]methylphosphonbthiolate. This is primarily
0003-2700/91 /0363-0457$02.50/0 0 199 1 American Chemical Society
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F
H
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OH
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Figure 1. Fragmentation scheme for chemical agent GB.
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Figure 3. System response to varying concentrations of chemical agent GB for the transition m l z = 141 99.
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Flgure 2. Fragmentatin scheme for the G analogue of chemical agent
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a contact agent because of the extremely low vapor pressure (0.0006 Torr at 20 "C), although its vapors and aerosols can be adsorbed through the respiratory tract (6). For detection purposes, chemical agent VX presents an additional problem because of its stickiness. VX is very easily adsorbed on surfaces and cannot be, quantitatively, transported through any tubing. To overcome this problem, a pad impregnated with silver fluoride is used at the entrance of the inlet tubing of the system. Silver fluoride chemically converts chemical agent VX to a molecule similar to chemical agent GB. The conversion of VX to its G analogue is 80% efficient and takes place via the following reaction: CIIH26N02PS + AgF CSHEOZPF + C,H,,NSAg +
The G analogue of VX is structurally similar to chemical agent GB and has proton affinity similar to that of GB. This makes it a good candidate for sensitive ionization when using API. Figure 2 shows the fragmentation pathway for the protonated molecular ion of the G analogue. The major fragment of the protonated G analogue ( m / z = 127) is m / z = 99. The system monitors the transition m / z = 127 99 for the purpose of detecting chemical agent VX.
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RESULTS AND DISCUSSION One of the objectives of our work was to demonstrate the reliable detection of low levels of chemical agents in ambient air. T o this end, we performed experiments to measure the system response to varying concentrations of chemical agents in air. We used six challenge concentrations in the range of 5-75 ppt. The system response a t each challenge concentration was measured in triplicate. The above procedure was repeated 4 times, over the course of a few days. The system response thus obtained was converted to a found concentra-
tion. Regression analysis was performed on the resulting data to obtain statistical parameters pertinent to describing the performance of the system. We followed the procedure used by the U S . Army Toxic and Hazardous Materials Agency (USATHAMA) to determine certified reporting limits (7). The principles of this method are described by Hubaux and Vos (8). This procedure consists of performing a weighted linear regression of the found versus target concentration. Both upper and lower confidence limits, a t any desired confidence level, can then be obtained. In this work, we used a confidence level of 95%. Based on this analysis, statistical parameters like the limit of detection (LOD) and decision limit (DL) can be calculated. LOD is the smallest true concentration that will be consistently detected. If the analyte is present in the sample stream a t the LOD concentration level, the probability that it will be detected is a t least 95%. True concentrations above the LOD are deemed detectable. DL is the maximum found concentration that will result, with a probability of 9570,from a stream containing no analyte. However, since the DL is usually less than the LOD, this will not constitute a false positive. These two statistical parameters contain all the information needed to assess a systems detection performance. GB. Figure 3 shows the typical response of the system a t the transition m / z = 141 99 for varying concentrations of chemical agent GB. Figure 4 shows the linear regression analysis with 95% confidence bounds for the found versus target concentration for chemical agent GB, following the procedure outlined above. The statistical parameters obtained from this analysis are LOD = 7.2 ppt and DL = 3.8 ppt. These results indicate that the API MS/MS system is capable of detecting chemical agent GB in air a t levels above 7 . 2 ppt, with good specificity. A degree of specificity is assured because of the use of tandem mass spectrometry to monitor the transition from the protonated molecular ion to a fragment ion. If a higher degree of specificity is required, transition from the protonated molecular ion to another fragment ion can be monitored. However, sensitivity is sacrificed because the secondary fragment ions are fairly weak compared to the primary
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ANALYTICAL CHEMISTRY, VOL. 63, NO. 5, MARCH 1, 1991
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Target Concentratlon (ppt) Figure 4. Plot of found concentration versus target concentration for chemical agent GB, with 95% confidence bounds.
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Target Concentratlon (ppt) Figure 6. Plot of found concentration versus target concentration for chemical agent VX, with 95 % confidence bounds.
ACKNOWLEDGMENT We thank Lanny Davis of Chemical Agents Munitions Disposal System, Tooele Army Depot, Tooele, UT, for his assistance during the course of this work.
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LITERATURE CITED
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Flgure 5. System response to varying concentrations of chemical 99. agent VX for the transition m l z = 127
fragment ions. The secondary fragment ions for chemical agent GB is m / z = 81. On monitoring the transition m / z = 141 81, the LOD is 14.1 ppt. VX. Figure 5 shows the typical response of the system to varying concentrations of chemical agent VX. (Note: The
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system used a AgF-impregnated pad to convert chemical agent VX to its G analogue, which was detected.) The results of the statistical analysis on the performance of the system for chemical agent VX are shown in Figure 6. The statistical parameters obtained from this analysis are LOD = 6 ppt and DL = 3.1 ppt. This indicates that the API MS/MS system is capable of detecting chemical warfare agent VX in air a t levels above 6 ppt. If one wishes to increase the degree of specificity, the transition m / z = 127 81 can be monitored. The limit of detection for this transition is 100 ppt.
I 1000
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(1) Syage, Jack A. Anal. Chem. 1990, 62, 505A. (2) Final Reports on New Concepts In Chemical Monitoring, Contract No. DAAA15-86-C-0107, prepared for the Program Manager for Chemical Demilitarization, Aberdeen Proving Grounds, Edgewood, MD. (3) Ketkar, S. N.; Dulak, J. G.:Fite, W. L.; Buchner, J. D.: Dheandhanoo, S. Anal. Chem. 1989, 6 1 , 260. (4) Kambara, H.; Kanomata, I. Anal. Chem. 1977, 49, 270. (5) Ketkar, S. N.; Fite, W. L. Rev. S d . Instrum. 1988, 5 9 , 387. (6) Chemical Stockpile Disposal Program, Report SAPEO-CDE-IS-87005, Sept 1987. (7) Department of the Army, US. Army Toxic and Hazardous Materials Aaencv. "Samolina and Chemical Analysis Quality Assurance Program", April '19f2. (8) Hubaux, A,; Vos, G. Anal. Chem. 1970, 4 3 , 849.
RECEIVED for review September 4,1990. Accepted November 19,1990. This work was supported by U S . Army Program Manager for Chemical Demilitarization, Aberdeen Proving Grounds, Edgewood, MD, under Contract No. DAAA15-86(2-0107.
