Instrumentation R. A. Yost Department of Chemistry University of Florida Gainesville, Fla. 32611
C. G. Enke Department of Chemistry Michigan State University East Lansing, Mich. 48824
Triple Quadrupole Mass Spectrometry for Direct Mixture Analysis and Structure Elucidation Quad Mass Filter
Ion Source
Quad Collision Chamber
Quad Mass Filter
Particle Multiplier
IF-X*»
^ ^ Sample Ionization
Ion Selection
Ion Fragmentation +/or Reaction
Product Ion Selection
Ion Detection
Figure 1 . Conceptual diagram of the triple quadrupole mass spectrometer showing each component and its function
A new technique of mass spectro metry is rapidly emerging in which tandem mass analyzers are used for separation and identification in a sin gle instrument. In this technique (MS/MS), several ionic species are generated from a sample; ions of a particular mass are selected for frag mentation; the selected ions are frag mented by one of several possible techniques; and the resulting frag ment ions are mass-analyzed. We re cently introduced the concept of a tri ple quadrupole mass spectrometer as a particularly simple and efficient ap proach to selected ion fragmentation (1). T h e instrument consists of, in se ries, a dual chemical ionization/electron impact (CI/ΕΙ) sample ionization source, a quadrupole mass filter, an RF-only quadrupole t h a t can be pres surized with a collision gas, a second quadrupole mass filter and an electron 0003-2700/79/A351-1251$01.00/0 © 1979 American Chemical Society
multiplier, as shown in Figure 1. T h e ion fragmentation process is per formed by collision-induced dissocia tion (CID) in which the ion acquires internal energy by collision with a neutral molecule. T h e RF-only qua drupole collision chamber provides fo cusing of scattered ions and is highly efficient (2). In this system, the select ed ion fragmentation process can pro vide enhanced selectivity and discrim ination over normal mass spectrome try without significant loss of sensi tivity.
A n A d d e d Dimension of Information
The added information contained in the fragmentation spectrum of each source ion species is of great value in several areas of mass spectrometry, especially the elucidation of organic
structures and the analysis of mix tures. In structure elucidation applica tions, fragment ions of any mass which appear in a compound's normal mass spectrum can be selected with the first mass analyzer. This parent ion is fur ther fragmented, and the mass spec trum of the resulting daughter ions is determined by scanning the second mass analyzer. A complete fragmenta tion map may be obtained by record ing the mass spectrum of each frag ment ion of a compound. Figure 2 is an example of such a map for cyclohexane. Note t h a t the normal electron impact mass spectrum, displayed along the diagonal (fragment ion m/z = parent ion m/z), is the only informa tion available without the added di mension of selected ion fragmenta tion. For analysis of mixtures, the molec ular ions for each component can be
ANALYTICAL CHEMISTRY, VOL. 5 1 , NO. 12, OCTOBER 1979 · 1251 A
Figure 2. Three-dimensional fragmentation map for cyclohexane
produced by soft ionization such as chemical ionization or field desorption and then separated by the first mass analyzer. Thus the molecular ion species can be selected for one compo nent at a time, the selected ion frag mented, and its fragmentation mass spectrum obtained by scanning the second analyzer. The added dimen sion in this case is the selectivity and discrimination achieved through mass separation of the molecular ions of the several components. The elimination of chemical noise that results can often improve the detection limit of the mass spectral technique (3). The use of mass spectral separation of the components of a mixture in MS/MS eliminates the time delays as sociated with the chromatographic separation used in GC/MS and LC/ MS. Because all the components are available at any time and in any order, only those components of particular interest need be analyzed. Each com ponent may be selected for as much or as little time as is required to deter mine its identity and its quantity. Continuous analysis of a sample is possible in such applications as atmo spheric analysis, without the time de lays associated with batch sampling for chromatographic analysis. Direct insertion probes and field or chemical desorption can be used to introduce involatile or thermally labile samples. Other Selected Ion Fragmentation and Tandem Mass Spectrometers
There are several other approaches to selected ion fragmentation, the most notable of which for analytical applications is Mass-Analyzed Ion Ki netic Energy Spectrometry, or MIKES (also called Collisional Acti vation Mass Spectrometry or CAMS, and Direct Analysis of Daughter Ions or DADI). This technique makes use of a double-focusing mass spectrome ter in which the magnetic sector pre 1252 A • ANALYTICAL CHEMISTRY,
cedes the electrostatic analyzer. Frag mentation between the sectors can be unimolecular (metastable ions) or collisionally induced. MIKES has been demonstrated as a technique for se lected ion fragmentation in such ap plications as structure elucidation (4-8) and mixture analysis (3, 9). The structure elucidation technique has been clearly described by Beynon (8). The technique for analysis of mixtures has been reviewed by Cooks in these pages (3). It is also possible to emulate the MIKES technique with a normal geometry double-focusing mass spec trometer (electric sector preceding the magnet) and a linked scan of both the electric sector field strength and ei ther the magnetic field or accelerating voltage (10). Ions enter the CID colli sion chamber in sector instruments with 3-30 keV of kinetic energy. The mechanism of the CID process at these high energies is fundamentally different from the process at the low kinetic energies (3-50 eV) of ions in the triple quadrupole instrument (11). True tandem mass spectrometers have been constructed to apply select ed ion fragmentation techniques to the study of interactions between ions and molecules (12). Two quadrupoles in tandem have been employed to study ion-molecule reactions (13), and triple quadrupole systems have been applied to study the photodissociation of ions (14, 15). However, it is the lowenergy CID process in the center quad that makes the triple quadrupole spectrometer described here particu larly well suited for analytical applica tions. Hunt and co-workers have re cently reported on the analytical ap plications of a triple quadrupole in strument constructed in their labora tory (16). Modes of Operation
There are three fundamental con trol parameters in the triple quadru
VOL. 5 1 , NO. 12, OCTOBER
1979
pole mass spectrometer. These are the mass selected by the first mass analy zer, the presence or absence of colli sion gas in the quad collision chamber, and the mass selected by the second mass analyzer. These parameters may all be varied independently or in com binations to provide a variety of useful modes of operation as enumerated and described below: • In order to obtain a normal mass spectrum (only one stage of mass anal ysis), the first mass filter is scanned with the second and third quadrupoles in RF-only (total-ion) mode. The colli sion gas may be present or not, since it does not significantly affect the number of ions reaching the detector. • A scan of the third quadrupole while the first mass filter passes a spe cific mass produces a spectrum of all the daughter ions from the selected parent ion. If the collision gas is ab sent, the unimolecular decomposition products ("mestastable" ion decompo sition) will be measured. • The spectrum of all parent ions that fragment to produce a given daughter ion is observed by scanning the first mass filter with the third quadrupole fixed on the daughter ion mass. • The observation of a specific neu tral mass loss is achieved by scanning both mass filters with a fixed differ ence in mass. The use of a double-fo cusing mass spectrometer for neutral loss spectra has been suggested re cently as a useful but complicated technique for structure elucidation (17).
• A specific parent/daughter ion transition is selected in single reaction monitoring (18), a technique analo gous to single ion monitoring in gas chromatography/mass spectrometry. • The quadrupole's linear mass scale and fast response permit rapid multiple reaction monitoring in which multiple parent/daughter ion pairs are observed. Mixture Analysis
As an example of the performance of the triple quadrupole mass spec trometer, the following sample which contains five components at equal concentration was chosen: 3-heptanone and n-heptanal (isomers of mo lecular weight 114), «-octane (isobaric with the other two at 114), cyclohex ane (84), and 2-pentanone (86). The mixture was ionized by 70 eV EI, al though CI would have simplified the mass spectrum. The CID spectra of the 114+ ion from the individual com ponents show unique fragmentation: 99+ (M-15) for 3-heptanone, 96+ (M18) for n-heptanal, and 70+ (C 5 Hi 0 + ·) for η-octane. In the CID spectrum of the 114+ ion in the mixture, it is possi ble to detect the individual compo-
Reference Spectra
Spectra of Selected Ions
Ion Fragmentation
43 n-Octane 43 114·. υ c 3
£ 1010"
Bruce R. Kowalski, Editor University of Washington A symposium sponsored by the Division of Computers in Chemistry of the American Chemical Society. This new collection constitutes an invaluable aid for every analytical chemist, instrument designer, and builder interested in the search for better measurement system control as well as up-to-date optimization and measurement analysis methods. Increased use of chemical measurements, combined with the >roliferation of computers in chemical aboratories, has prompted a drive for new and improved methods to design and control experiments and to analyze the wealth of data that can be generated.
f
The results of this research effort are discussed in 12 chapters covering the development and application of new mathematical and statistical analysis methods to extract useful chemical information from chemical measurements. CONTENTS Optimization Methodology in Chemistry · ARTHUR and Experimental Data Analysis · Abstract Factor Analysis « TargetTransformation Factor Analysis · Application of Factor Analysis to the Study of Rain Chemistry · Electron Spin Resonance of Spin Labels · Stirred-Pool ControlledPotential Chronocoulometry · Application of Nonlinear Regression Analysis to Chemical Data · Structure-Activity Studies · Enthalpy-Entropy Compensation · How to Avoid Lying with Statistics · SIMCA: A Method for Analyzing Chemical Data in Terms of Similarity and Analogy 288 pages (1977) $21.00 clothbound LC 77-9088 ISBN 0-8412-0379-2 SIS/American Chemical Society 1155 16th St., N.W./Wash., D.C. 20036 Please send copies of SS 52 Chemometrics at $21.00 per copy. D Check enclosed for $ . D Bill me. Postpaid in U.S. and Canada, plus 40 cents elsewhere. Name Address City
Stale
Zip
10- s 10" 4 Collision Gas Pressure (N2)
(torr) 10-
Figure 6. Effect of collision gas (N 2 ) pressure on CID efficiency for methane C H 4 + · at ion axial energy of 10eV
chemical and electrical noise levels, and the lowest measurable signal level. The electrical noise in the system is typically 3 X 10~ 1 3 A. The two stages of mass separation often make it pos sible to reduce chemical noise (ions detected from other than the desired reaction) to well below the 1 0 - 1 3 A level. In such a case, at the extreme sensitivity limit, the peak height is quantized by the integer number of ions which reach the detector during the scanning time of the peak. The de tection of 4 ions would give an S/N of 2 and, for methane, would require 6 fg of sample. T h e detection limit for methane has been determined experi mentally to be 16 femtograms by mea suring a sample of 10 ppm CH 4 in N2 at a sample flux of 20 femtograms per sec of CH4. The large excess of N2 is required to increase the ion source pressure so that it can be accurately measured and the sample flux calcu lated. The selectivity of monitoring the CH4 + - -* CH3 + reaction has ef fected a two order of magnitude im provement in detection limit com pared to that obtained by simply mon itoring the CH 4 +·, CH 3 +, or CH 2 +· ions from electron impact. This im provement is due to the elimination of the chemical noise introduced by background 1 4 N + -, 15 N+· and 1 6 0+· peaks. The selected ion fragmentation ca pability of the instrument produces only a small loss in transmission and sensitivity, and produces a significant gain in selectivity. Indeed, in the nor mal case where the system is limited by chemical rather than electrical noise (3), a substantial improvement
1262 A · ANALYTICAL CHEMISTRY, VOL. 51, NO. 12, OCTOBER 1979
in detection limit can be achieved as was observed for methane. T h e detec tion limit of approximately 1 0 - 1 5 mole is made possible by the high efficiency of every component of the system. The detection limit for a higher mass organic compound, nitroben zene, has also been determined experi mentally. The transition N 0 2 C 6 H 5 + · —»· CeH5 + was monitored at unit mass resolution in both mass filters, with the parent ion produced by electron impact on a sample of 10 ppm nitro benzene in N2. A detection limit of 120 femtograms (S/N = 2) was obtained with a sample flux of 200 femtograms/ sec. In comparison, for the M I K E S technique, Cooks has estimated a de tection limit of 10 pg for the 140 + -*• 123 + transition of protonated nitrophenol ions produced by CI (22). Al though consumption of only femto grams is required for recording the single reaction, actual sample size is significantly larger than this and is de pendent on the sample inlet used. Total consumption of a sample intro duced by direct probe should make it possible to detect quantities of indi vidual components at close to these detection limits. Conclusions
T h e CID process performed in the strong focusing field of an RF-only quadrupole is efficient and effective in producing characteristic spectra of selected ions. T h e kinetic energy inde pendence of the mass resolution is ideal for collision product analysis. The lack of interdependence in the control of the two mass filters makes
Topics in . . .
Chemical Instrumentation—II A volume of reprints from the Journal of Chemical Education Galen W. Ewing, Editor This new collection of selected reprint articles from the "Topics in Chemical Instrumentation" column in the JOURNAL OF CHEMICAL EDUCATION provides excellent coverage of the field from 1970 through 1975. In order to furnish the most complete, up-to-date information on the subject many of the authors have added supplemental material to their papers. The 36 reprints are listed according to subject matter rather than by chronological order. This useful collection will be of particular interest to analytical chemists, college chemistry faculties, research chemists, librarians, and those seeking an introduction to the state of the art. CONTENTS A Review of Wavelength Calibration Methods for Visible-Range Photoelectric Spectrophotometers · Instrumentation for Fluorescence and Phosphorescence · Optical Rotatory Dispersion and Circular Dichroism · Atomic Spectroscopy Atomization Systems · Multiplex Spectrophotometry · Nuclear Magnetic Resonance Spectrometers · X-Rays and Electrons in Analytical Chemistry, with Emphasis on Instrumentation · Infrared Detectors · Nuclear Quadrupole Resonance Spectroscopy · Electron Spectroscopy Instrumentation · Step Perturbation Relaxation Techniques · Scanning Electron Microscopy · Reference Electrodes · Anodic Stripping Voltammetry · The Measurement ot Electrolytic Conductance · Thermal Analysis Techniques · Analytical Applications of High Resolution Mass Spectrometry · Liquid Chromatography Detectors · Recent Developments in Instrumentation for Liquid Chromatography · Current Trends in Gel Permeation Chromatography · Instrumentation for Thin Layer Chromatography · Centrifugal Analyzers—A New concept in Automation for the Clinical Chemistry Laboratory · Continuous Flow Measurement of Beta Radiation Using Suspended Scintillators · Nuclear Radiation Detectors · Laboratory Automation—A Case History · Laboratory Integrators · Lock-in Amplifiers · Signal Averagers · Home-Built Equipment in the Teaching Laboratory · Sir Charles' Bridge · An Introduction to Microelectronics · Inert Atmosphere Enclosures · Analytical Instrumentation: 1940-41 Vintage · Calculators for the Chemist • Analysis of Gases in Metals: Fusion and Extraction Methods · Specialized Instruments for the Determination of Sulfur by the Combustion Method
it easy to implement the various analytical modes. T h e system can be used to detect species present in a mixture including isomers without prior separation at the 1 0 - 1 5 mole level. T h e capability to select a desired initial mass and specific collision product mass reduces chemical noise dramatically. For structure elucidation applications, the spectra of selected functional moieties in the molecule may be obtained. Among the many other promising applications of the selected ion fragmentation technique is the analysis of isotopically labeled samples, in which the first mass filter can eliminate interferences from molecules t h a t are not completely labeled.
Acknowledgment We wish to acknowledge the work of the MSU Chemistry D e p a r t m e n t Machine Shop headed by Russ Geyer, and master machinist Len Eisele who constructed much of the instrument. We would also like to express our gratitude to Kaz Latven, John Chakel and Fritz Allen who helped to get the ins t r u m e n t functioning and t o demonstrate its application. Finally, we would like to acknowledge the invaluable time spent in the laboratory of J i m Morrison a t La Trobe University and helpful discussions with Graham Cooks and Chuck Sweeley.
References (1) R. A. Yost and C. G. Enke, J. Am. Chem.Soc, 100,2274-75(1978). (2) R. A. Yost, C. G. Enke, D. C. McGilvery, D. Smith, and J. D. Morrison, Int. J. Mass Spectrom. Ion Phys., 30,127136 (1979).
S I S / A m e r i c a n C h e m i c a l Society 1155 16th St., N.W./Wash., D C . 2 0 0 3 6 Please send copies of Chemical Instrumentation—II at $12.00 per copy. CI Check enclosed for $ . D Bill me. Postpaid in U.S. and Canada, plus 40 cents elsewhere. Name Address
1264 A ·
Zip
ANALYTICAL CHEMISTRY, VOL. 5 1 , NO. 12, OCTOBER
This work was supported in part by the Office of Naval Research.
Chris Enke (left) and Rick Yost developed the triple quadrupole mass spectrometer at Michigan State University where Chris is professor of chemistry and Rick was a graduate fellow with support from the National Science Foundation and Analytical Division of ACS (sponsored by the Upjohn Company). Rick is currently assistant professor of chemistry at the University of Fla., Gainesville and is pursuing a research program in computer applications and modern instrumentation with special emphasis in mass spectrometry. The research program in Chris' lab at Michigan State University includes the development and application of computer-based instrumentation in optical spectroscopy, electroanalytical chemistry, and mass spectroscopy.
310 p a g e s (1977) h a r d b a c k $12.00 ISBN 0-8412-0367-9 LC 73-153064
City
(3) R. W. Kondrat and R. G. Cooks, Anal. Chem., 50, 81A-92A (1978). (4) R. G. Cooks and J. H. Beynon, MTP Int. Rev. Sei., Ser. II, 5,159 (1975). (5) F. W. McLafferty, P. F. Bente, R. Kornfeld, S. C. Tsai, and T. Howe, J. Am. Chem. Soc, 95, 3886 (1973). (6) U. P. Schlunegger, Angew. Chem. Int. Edn., 14,679-88(1975). (7) K. Levsen and H. Schwarz, Angew. Chem. Int. Edn., 15, 509-19 (1976). (8) M. H. Bozorgzadeh, R. P. Morgan, and J. H. Beynon, Analyst, 103, 613-22 (1978). (9) F. W. McLafferty and F. M. Bockhoff, Anal. Chem., 50, 69-76 (1978). (10) R. J. Stradling, K. R. Jennings, and S. Evans, Org. Mass Spectrom., 13 429-30 (1978). (11) Manuscript in preparation. (12) J. H. Futrell and T. O. Tièrnan in "Ion-Molecule Reactions," J. L. Franklin, Ed., Chap. 11, Plenum, New York, 1972. (13) T.-Y. Yu, M. H. Cheng, V. Kempter, and F. W. Lampe, J. Phys. Chem., 76, 3321-30 (1972). (14) M. L. Vestal and J. H. Futrell, Chem. Phys. Lett., 28, 559-61 (1974). (15) D. C. McGilvery and J. D. Morrison, Int. J. Mass Spectrom. Ion Phys., 28, 81-92 (1978). (16) D. F. Hunt and J. Shabanowitz, 27th Annual Conference on Mass Spectrometry and Allied Topics, Seattle, Wash., June 1979; paper FAMOC2. (17) M. J. Lacey, C. G. MacDonald, Anal. Chem., 51,691-95(1979). (18) R. W. Kondrat, G. A. McClusky, and R. G. Cooks, Anal. Chem., 50, 2017-21 (1978). (19) F. W. McLafferty, "Interpretation of Mass Spectra," 2nd Ed., pp 95-6, W. A. Benjamin, Reading, Mass. 1973. (20) Manuscript in preparation. (21) G. Eadon, C. Djerassi, J. H. Beynon, and R. M. Caprioli, Org. Mass Spectrom., 5,917-33(1971). (22) T. L. Kruger, J. F. Litton, R. W. Kondrat, and R. 6. Cooks, Anal. Chem., 48, 2113-19(1976).
1979
