Anal. Chem. 1989, 6 1 , 1093-1099 (18) Benninghoven, A,; Rudenauer, F. G.; Werner, H. W. I n Secondary Ion Mass Spectrometry; John Wiley & Sons: New York, 1987; Chapter 5.1.3. (19) Ziegler, J. F.; Biersack, J. P.; Cuomo, G., TRIM-The Transport of Ions in Matter, based on The Stopping and Range of Ions in Matter; Pergamon Press: New York, 1985. (20) Benninghoven, A,; Riidenauer, F. G.: Werner, H. W. I n Secondary Ion Mass Spectrometry; John Wiley & Sons: New York, 1987; Chapter 5.1.6.2. (21) Sunner, J.; Ikonomou, M. G.;Kebarle, P. Int. J. Mass Spectrom. Ion Processes 1988,82. 221-237. (22) Beuhler. R. J.: Friedman. L. Int. J . Mass Snectrom. Ion Processes 1987,78,1-15. (23) Benninghoven, A.; Riidenauer, F. G.; Werner, H. W. I n Secondary Ion Mass spectrometry: John Wiley 8 Sons: New York, 1987: Chapter 5.1.6.7.
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(24) Pachuta, S. J.; Cooks, R. G. I n Desorption Mass Spectrometry; ACS Symposium Series; American Chemical Society: Washington, DC, 1985; pp 1-42. (25) Benninghoven, A.; Rudenauer, F. G.; Werner, H. W. I n Secondary Ion Mass Spectrometry: John Wiley 8 Sons: New York, 1987; Chapter 5.1.6.5. (26) Van Ooij, W.; Brinkhuis. R. H. G. Proceedings of the VIth International Conference on Secondary Ion Mass Spectrometry, Versailles, France, 1987.
RECEIVED for review September 21,1988. Accepted February 13, 1989. Work supported by the Office of Health and Environmental Research, Office of Energy Research, DOE under Contract 4AA901.
Ion Mobility Spectrometry of Halothane, Enflurane, and Isoflurane Anesthetics in Air and Respired Gases G . A. Eiceman,*JD. B. Shoff, C. S. Harden, and A. P. Snyder U S . A r m y Chemical Research, Development, and Engineering Center SMCCR-RSL, Aberdeen Proving Ground, Maryland 21020 P. M. Martinez and M. E. Fleischer Department of Chemistry, New Mexico State University, Las Cruces, New Mexico 88003 M. L. Watkins
Memorial General Hospital, Las Cruces, New Mexico 88005
Three common gaseous anesthetics, halothane, enflurane, and isoflurane, were Characterized by using ion mobility spectrometry (IMS)/mass spectrometry, and the dependence of product Ion distributions on temperature and concentration was evaluated. At 40 'C and 500 ppb, negative ion mobility spectra In air largely consisted of monomer or dimer adducts with Br- or CI- formed through dissociative electron capture of molecular neutrals. With increased temperature or decreased vapor concentrations, declustering and dissociation of product ions became pronounced. Ion-molecule reactions in the drift region of the IMS were evident as distortions in peak shape In the mass-resolved mobility spectra and in variable reduced mobllltles for the same Ions. A portable hand-held IMS was used for convenient, real-time detection of enflurane In respired gases following a controlled inhalation episode.
INTRODUCTION Volatile halogenated anesthetics (VHAs),based principally on fluorinated and chlorinated two- or three-carbon alkane or ether structures, have become medical and occupational health concerns due to chronic or acute inhalation exposures (1). These anesthetics can be found in blood (2-4), respired air (5),and operating-theater atmospheres (6-8) under normal clinical conditions, and subsequent investigations provided strong evidence that VHAs caused episodes of organ toxicity Permanent address: Department of Chemistry, Box 30001-Dept. 3C, New Mexico State University, Las Cruces, NM 88003.
(9) and mortality (10) in surgical patients. Furthermore, possible liver damage to hospital surgical personnel from chronic, subclinical environmental exposure to VHAs has been suggested (11). Poisonings from solvent abuse (12) represent related but somewhat unpredictable medical obstacles. Gas chromatography (GC) has been used for VHA determinations in blood (13)and in operating-theater atmospheres (14) since the early 1970s and exhibited good selectivity and high sensitivity (2, 3,5-8,12-14), which were largely due to the characteristics of electron capture detectors (ECDs). While GC was well-suited for analysis of discrete samples, continuous monitoring of VHA concentrations in air or blood was found to be technically cumbersome. Other technologies (15-21) were proposed for VHA or solvent sensing; however, they too proved to be insensitive, unselective, or too expensive for practical clinical utility. Thus, analytical techniques are needed (8,12)for the determination of VHAs in ambient air and respired gases within a short time period as well as on a continuous basis with sub-part-per-million detection limits. Relatively inexpensive, continuous, organic vapor detectors based on ion mobility spectrometry (IMS) instrumentation have been developed for portable air monitoring (22,23). In IMS, analyte vapors are drawn into a reaction region where analyte molecules are collisionally ionized through proton or electron exchange from reactant ions created in the reaction region. The resultant product ions are then characterized by using gaseous ionic mobilities in a drift region that contains a weak electric field. While ion integrity during transport through the IMS drift region cannot always be assumed (24, 25), a more common disabling factor is unfavorable chemistry of product ion formation at atmospheric pressures in the IMS reaction region. This can be manifested as poor electron (or
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proton) capturing properties for a molecule, fragmentation of molecular ions, formation of complex molecular clusters, or competitive charge-exchange reactions with background interferents. Thus, the suitability of IMS for VHA sensing in ambient and respired air should be governed principally by the characteristics for the ionization chemistry of VHAs in air, and a thorough examination of ion-molecule chemistry of VHAs is a pivotal aspect to any eventual clinical or diagnostic use of IMS. Dissociative electron capture has been considered generally the primary ionization mechanism for halocarbons and leads to the creation of gaseous halide ions as principal product ions (26-28). Associative electron capture can occur with some perhalogenated compounds such as sulfur hexafluoride (29), but negative molecular ions are not commonly observed in ECDs or IMS for halocarbons. Exceptions arise when chloride ions are used as the reagent ion, in which case molecular halide ion adducts in IMS (30) or chloride additions to double bonds in chemical ionization mass spectrometry (31) have been shown to occur. The influence of temperature and vapor concentrations on ion-molecule reactions in the reaction and drift regions of an IMS has not been widely investigated, with the exception of a study on reactant ion composition (32)and recent reports on monomer-dimer equilibria (24) and fragmentation of butyl acetates in the IMS drift region (25). Temperature increases in IMS were shown to lower the extent of hydration in reagent ions, shift the amount of ion-molecule clustering from dimers to monomers, and promote rearrangement fragmentations of product ions in the IMS drift region. In each of these studies, positive ions were examined, but there have been no comparable studies in IMS for negative ions. A major objective of this study was to determine the atmospheric pressure chemical ionization (APCIj properties for the three most common VHAs (81, halothane (CF3CHBrC1), enflurane (CHClFCF20CHF2),and isoflurane ICF,CHClOCby investigating the negative ion products created in air at ambient pressure by use of IMS. Ion mobility spectral signatures for these VHAs were mass-identified by IMS/mass spectrometry (MS), and product ion distributions were found to be sensitive to both vapor concentration and temperature. These findings appear to provide additional information to the current understanding of electron capture mechanisms that have been proposed for ECDs. Furthermore, due to the importance of VHAs in the medical and diagnostic communities and as a practical demonstration of a potential utility of IMS in medical or environmental sensing, a commercial, hand-held IMS was used to screen for the presence and clearance of enflurane following a subclinical inhalation episode. EXPERIMENTAL S E C T I O N Instrumentation. A PCP, Inc., (West Palm Beach, FL) Model MMS-290 ion mobility spectrometer/mass spectrometer (IMS/MS) was equipped with a 12.5-mCi63Nisource and a Nicolet computer for hardware control and signal processing. Drift and carrier gases were generated from ambient air with a Model 377-12 Addco Pure Air Generator (Addco Instruments, Inc., Clearwater. FL) so moisture was
