Anal. Chem. 1990, 62, 2162-2172
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Tandem-in-Space and Tandem-in-Time Mass Spectrometry: Triple Quadrupoles and Quadrupole Ion Traps Jodie V. Johnson and Richard A. Yost*
Chemistry Department, University of Florida, Gainesuille, Florida 3261 1-2046 P a u l E. Kelley a n d Donald C . Bradford Finnigan M A T , ,355 River Oaks Parkway, S a n Jose, California 9515134- 1991 Tandem-In-the and tandem-In-space MS/MS on quadrupole Ion trap (ITMS) and triple quadrupole (TQMS) tandem mass spectr&ers, respectlvely, were compared by evakrdng the MS/MS daughter spectra, efflclencles of colllslon-Induced dlssoclatlon (CID), limlts of detection, and dynamic ranges obtalned for the methane posltlve chemical Ionization (PCI)-CID of two alkylphosphonates. Although the yield of daughter ions Is dependent upon a number of instrumental parameters on both instruments, with judicious selection of parameters the ITMS and TQMS both ylelded daughter ions of slmllar relative abundances. The ITMS had greater efficiencies of fragmentatlon, cdlectlon, and mass selection and transmlsslon of the daughter Ions to the detector. Wlth PCI-MS/MS analysis of dllsopropyl methyiphosphonate standards introduced via caplllary gas chromatography, full daughter spectra could be obtalned for as little as 15 pg and 1.5 ng injected for the ITMS and the TQMS, respectlvely. Limlts of detection were detembted to be approxhnately 5 pg for both the ITMS (with full daughter scan) and the TQMS (wlth sekcted reactlon monltorkrg of the parent Ion to Its most abundant daughter Ion).
INTRODUCTION The rapidly increasing use of tandem mass spectrometry (MS/MS) since it was first commercialized a decade ago has been due to its successful application to trace mixture analysis (1-3). Although sector and hybrid instruments have contributed significantly in this area, the majority of applications of tandem mass spectrometry to the determination of trace analytes in complex matrices has been performed with triple quadrupole mass spectrometers (TQMS) (2). Indeed, partsper-billion and parts-per-trillion limits of detection have been achieved for analytes in such complex matrices as urine, blood, animal and plant tissue extracts, and environmental samples. The quadrupole ion trap mass spectrometer (ITMS) represents a new approach to instrumentation for tandem mass spectrometry (4-13). However, the manner in which the quadrupole ion trap performs MS/MS differs significantly from the traditional MS/MS performed with triple quadrupole and sector MS/MS instruments. Tandem mass spectrometry consists of several sequential processes: ionization of sample molecules, mass selection of parent ions, collisioninduced dissociation (CID) of the parent ions with neutral gas molecules to produce daughter ions, and mass analysis and detection of these daughter ions. For tandem mass spectrometry with quadrupole and sector MS/MS instruments, these processes occur sequentially in separate regions of the instrument and, thus, MS/MS is tandem-in-space (Figure 1). With the quadrupole ion trap, all these processes occur sequentially in the same physical space, and thus, MS/MS is tandem-in-time (Figure 1). The instrumentation and operation of the ITMS have been described in several articles (9-13) and a recent book details the fundamentals and applications of quadrupole ion traps (14).
With the triple quadrupole and other "beam" tandem mass spectrometers, a continuous beam of ions is transmitted through the instrument while mass selection and CID of the parent ion continuously occur in separate regions of the instrument (Q1and Q2, respectively, for TQMS), independent of time (Figure 2a). The only time-dependent function is the mass analysis of the daughter ions by the second mass analyzer (Q3). With the ITMS being tandem-in-time, a pulse of parent ions is created and parent ion selection, CID, and daughter ion mass analysis are implemented by a timing sequence or scan function (shown for CI-MS/MS in Figure 2b). This scan function controls when each event occurs largely by controlling the rf voltage level applied to the ring electrode and the resonant excitation or CID voltage applied across the endcap electrodes. For chemical ionization (15-19), the rf voltage is set to a low value such that the low m / z CI reagent ions (created when the electrons are "gated" into the trap) are efficiently stored (period A). Following this initial electron ionization period, the rf voltage on the ring electrode can be increased to allow efficient storage of sample ions created from ion-molecule reactions with the CI reagent ions during the CI reaction period (period B). All the ions of m / z below that of' the parent ion are then ejected from the ion trap by raising the rf voltage on the ring electrode (period C). The trapping rf voltage is then lowered to an appropriate level for storing the daughter ions of interest (period D). Tandem mass spectrometry (MS/MS) is achieved during period E by applying an auxiliary ac (resonant excitation) voltage across the endcap electrodes. When the resonant excitation voltage has the same frequency as the secular frequency of an ion, that ion begins to resonate, increasing its kinetic energy and orbit and undergoing collisions with the helium buffer gas (approximately 1 ml'orr) normally present in the ion trap. Provided the conversion of its kinetic energy into internal energy during collisions is sufficient, a parent ion can undergo collision-induced dissociation (CID) to produce daughter ions. These daughter ions will be trapped if their m / z falls above the low m / z cutoff of the ion trap. Finally, the trapping rf voltage is scanned, sequentially ejecting to the detector and, thus, mass analyzing the daughter ions in the ion trap (period F). Here we report the results of our comparison of triple quadrupole tandem-in-space mass spectrometry and quadrupole ion trap tandem-in-time mass spectrometry with respect to mass spectral characteristics, CID efficiencies, limits of detection, and linear dynamic range obtained for the methane PCI-CID analysis of two alkylphosphonates. EXPERIMENTAL SECTION Reagents and Samples. Diethyl ethylphosphonate (DEEP, MW 166) and diisopropyl methylphosphonate (DIMP, M W 180) were provided by Dr. Pete Synder at the U.S. Army Chemical Research, Development, and Engineering Center (Aberdeen Proving Grounds, MD) and were used as provided. For quantitation, serial dilutions were prepared from a methanol stock solution of DIMP. Helium (Liquid Air Corp., San Francisco, CA) was used as an ITMS buffer and CID gas at an indicated chamber
/c: 1990 American Chemical Society 0003-2700/90/0362-2162$02.50/0
ANALYTICAL CHEMISTRY, VOL. 62, NO. 20, OCTOBER 15, 1990
Tandem-in-Space:
Tandem-in-Time:
ionlralion Mass Analysis Dissoclation Mass Analysis
Triple Quadrupole
Quadrupole Ion Trap
Detection
Figure 1. Two different tandem mass spectrometers: the triple quadrupole and the quadrupole ion trap, which are tandem-in-space and tandem-in-time, respectively. a) Fl
ament
TOMS
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0 : RF L DC 02 RF Voltoge
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A-El of Cl Reagent Gas and Formotion of Cl Reagent Ions &Reaction of CI Reagent Ions with Neutral Somple Molecules t o form Sample Ions C-Selection of Parent Ian D-Selection of Daughter ions' Mass Range E-CIC of the Parent Ian F-Scan Resultant Daughter Spectrum
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Ring RF
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an Resonant Excitation
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Figure 2. Schematic representation of the daughter scan mode for (a) a triple quadrupole tandem mass spectrometer (TQMS) and (b) a quadrupole ion trap mass spectrometer (ITMS). pressure of 1.0 X Torr. Methane (UHP grade, Matheson Gas Products, Morrow, GA) was used as a CI reagent gas in the ITMS and the TQMS at the pressures indicated in the text. Nitrogen, helium, and argon (Liquid Air) were used as CID gases in the triple quadrupoles at the pressures indicated in the text. Instrumentation. The initial triple quadrupole characterization of these compounds was performed on a Finnigan MAT TSQ45 (Finnigan MAT, San Jose, CA) with a Finnigan MAT 9610 GC, while the evaluation of sensitivity and linear dynamic range was performed on a Finnigan MAT TSQ70 interfaced with a Varian 3400 GC (Varian Instruments, Walnut Creek, CAI. All quadrupole ion trap data were obtained on a Finnigan MAT ion trap mass spectrometer (ITMS) interfaced with a Varian 3300 GC. Samples were introduced either via a variable leak valve (Series 203 valve, Granville-Phillips, Boulder, CO) or via a fused silica open tubular (FSOT) capillary GC column. Gas pressures were measured on the ITMS by a Bayard-Alpert ionization gauge (Granville-Phillips) mounted on the vacuum chamber. The helium buffer gas was admitted through the GC/MS open-split interface transfer line as a makeup gas. With
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a flow rate of approximately 1 mL/min helium out of the GC open-split makeup line, a chamber pressure of approximately 1.0 X Torr was usually obtained. Measurements with a capacitance manometer (Baratron 390HA, MKS Instruments, Burlington, MA) showed that under these conditions, the actual helium pressure inside the ion trap was approximately 1 mTorr. The ion source pressure on the TSQ45 was measured with a thermocouple gauge (Granville-Phillips) and the pressure sensing electronics provided with the instrument. The CID pressure was measured with a DV-8 thermocouple gauge tube and NV-8 gauge controller (Teledyne Hastings-Raydist, Hampton, VA). The ion source pressure and the CID gas pressure on the TSQ70 were monitored with separate Convectron thermocouple gauges (Granville-Phillips) and the electronics provided with the TSQ70. The pressures in the analyzer regions of both the TSQ45 and the TSQ70 were measured with Bayard-Alpert ionization gauges (Granville-Phillips) mounted on the vacuum manifold and controlled by the instruments' electronics. Unless specified in the text, all pressures are those indicated directly from the meters, with no corrections for the type of gas or sample used. Procedures. EI. Electron ionization was accomplished on the ITMS at an rf level corresponding to a low m/z cutoff of 10 amu with varying ionization times indicated in the text. The ion trap assembly was maintained at 100 "C throughout all the experiments. E1 was accomplished on the TSQ45 with a 70-eV electron energy, 0.2-mA emission current, and an ion source temperature of 100 "C. PCI. For the characterization of methane PCI of DEEP with the ITMS, DEEP was introduced into the ITMS vacuum chamber via a variable leak valve such that a constant level (approximately 0.1 x low5Torr) was present in the ion trap. For studies of the effect of the CI reaction time, the electron ionization time (usually 0.1 ms) and all other time periods were held constant while the CI reaction period was varied. The trapping rf level during ionization was kept at 5 amu while all other rf levels were kept at 12 amu. Mass spectra were acquired by scanning from m/z 12 to 400 in 2 s with 16 microscans. Methane PCI was achieved on the TSQ45 with an indicated ion source pressure of approximately 0.8 Torr methane, 100-eV electron energy, and a 100 "C ion source temperature. Methane PCI of DIMP on the TSQ70 was accomplished with approximately 2 Torr methane, 100-eV electron energy, and 100 "C ion source temperature. TQMS M S / M S Studies. For the collision-energy-resolved breakdown curves on the TSQ45, helium and nitrogen were used as CID gases at indicated collision quadrupole (Q2) pressures of approximately 1mTorr (actual pressures were approximately 1.4 and 1.0 mTorr, respectively). The collision energies (0-30 eV) were taken as the offset voltage of the Q2 referenced to the ion source, which was at ground. Due to the penetration of the electric fields of the ion lenses at the ion source exit and at the entrance and exit of Q2, the absolute collision energies may be slightly different. The collision gas pressure resolved breakdown curves were obtained at a Q2 offset voltage of 20 eV while the pressure of the nitrogen collision gas was varied from 0.1 to approximately 5 mTorr. ITMS M S I M S Studies. For MS/MS studies in the trap, the helium buffer gas (approximately 1mTorr) also served as the CID gas. With the ITMS, the frequency and magnitude of the resonant excitation voltage, the time for which the resonant excitation voltage is applied, and the trapping rf voltage during resonant excitation are all interrelated. As such, the effects of each parameter upon the MS/MS of a parent ion were studied by varying only one of the parameters while keeping the others constant. The appropriate value of each parameter is specified in the text or figures. The frequency of the resonant excitation voltage w a first ~ optimized at a particular rf level and then the effects of resonant excitation voltage and resonant excitation time were investigated at the resonant excitation frequency determined to yield maximum CID. The collision-energy-resolved breakdowm studies were accomplished on the ITMS by varying the magnitude (0-4000 mV) of the resonant excitation voltage. The exact collision energy or kinetic energy of the parent ion was not determined. As the ITMS has been determined to operate most efficiently with approximately 1 mTorr helium (4-6,20), the effects of buffer gas pressure were not investigated.
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Table I. Experimental Conditions for GC/MS/MS Determination of DIMP Standards on Triple Quadrupole (TQMS) and Quadrupole Ion Trap (ITMS) Tandem Mass Spectrometers
Mass Spectrometry TQMS: 100 eV, 100 "C, 2 Torr CH, Torr CH, ITMS: 100 "C, 3.5 X ionization for 13 ms at rf = 7 amu CI reaction for 175 ms at rf = 15.8 amu CID TQMS: 1.7 mTorr (actual) argon, 30 eV ITMS: 1 mTorr helium, 800 mV resonant excitation voltage CID for 15 ms at rf = 50 amu parent ion q = 0.25 resonant excitation frequency of 98 797 Hz daughter ion analysis TQMS: full scan: 50+ 225+, 1 s SRM" of 181' 97+, 0.1 s ITMS: full scan: 50+ -* 225+, 0.248 s/pscan, 13 pscans
methane PCI
- -
Gas Chromatography TQMS: 30 m SE-54 FSOT ITMS: 28 m DB-5 FSOT inj port temp 250 "C GC/MS interface temp 250 "C column temp program 50 "C (1min, split and sweep closed) 50 to 165 "C at 30 OC/min sample size 1.5 pL, splitless column
Table 11. E1 and PCI Normal Mass Spectra of DEEP Obtained with a TQMS and an ITMS"
relative abundance PCI ITMS TQMS ITMS
%
E1 m/zb
333 207 195 167 166 139 138 137 122 121 111 110 109 94 93 91 82 81 65
TQMS
