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Anal. Chem. 1985, 57, 2918-2924
New Scan Modes Accessed with a Hybrid Mass Spectrometer John N. Louris, Larry G. Wright, and R. Graham Cooks* Department of Chemistry, Purdue University, West Lafayette, Indiana 47907
Alan E. Schoen Finnigan MAT, Barkhausenstrasse 2, Postfach 14 40, Bremen 12, West Germany
A hybrld BEQQ mass spectrometer Is used to Implement several new types of tandem mass spectrometry (MS/MS) experiments. Each experiment utlllzes reactlons occurrlng In two separate reglons of the mass spectrometer, whlch are followed by scannlng one or more of the flelds associated wlth the magnetic sector, the electric sector, and the quadrupole mass fllter. The types of scans that result Include a consecutlve neutral loss scan whlch Increases the molecular speclflclty over that avallable in conventlonal neutral loss scans. Recognitlon of the members of partlcular chemical classes In mixtures Is also facllltated by a new selective type of parent scan. Speclflc compounds can be characterized by use of a new selectlve daughter scan, whlch dlsplays a specific subset of the products arlslng from a partlcular Ion. These scan modes are consldered in the context of a systematlc evaluation of the MS/MS technique. This approach has revealed additional new scans, Including a scan that 88lects for reaction lntermedlates. Improved performance In conventlonal MS/MS scans Is also demonstrated. For example, use of the quadrupole as a supplementary mass filter improves resolution in daughter spectra recorded by scannlng the electric sector voltage (Le., mass-analyzed Ion kinetic energy spectra). The use of thls hybrld Instrument for recording doubly charged Ion spectra is also Illustrated.
We attempt two things in this paper, (i) to provide a rational framework to accommodate the increasing number of mass spectral scans and (ii) to introduce a number of new scans, including complex new types consisting of combinations of parent, daughter, and neutral loss (gain) scans. The vehicle for this discussion is a hybrid BEQQ spectrometer that consists of a magnetic sector (B), an electrostatic sector (E),and two quadrupoles (Q). A systematic presentation of the mass spectrometry experiment is given in general terms and is independent of the particular mass spectrometer configuration. The BEQQ instrument (Figure 1) has been described in detail, and its capabilities for conventional MS/MS scans (parent, daughter, and neutral loss) have been illustrated (14). An attractive feature of this mass spectrometer is the versatility embodied in the four different types of analyzers (B, E, and Q, together with retarding potential analysis necessary in coupling the sector and quadrupole sections). Indeed, it has been pointed out that dozens of scan modes are potentially available using this instrument although they have not been specifically delineated ( 2 , 5 ) . This paper gives examples of some of these new scans in the context of the systematization of MS/MS scan types. The examples of applications given are intended simply to establish feasibility. Experiments based on more than two consecutive reactions are excluded from discussion as, with a single exception, are charge changing collisions. Incorporation of both these features represents a straightforward extension of the concepts presented here. In addition, no consideration is given to
high-resolution MS/MS experiments, nor are methods that provide additional information, such as internal energy resolution, discussed. Again, both of these capabilities have already been demonstrated (4,641for simpler scan types and they can be utilized by straightforward extensions of the experiments described here. In addition to the new scan modes, space is devoted to experiments in which improved performance is sought from established scans by using the quadrupole mass filter for supplementary mass analysis. In implementing the new scans, the accelerating voltage has not been used as a variable, although this could have been done with results similar to those reported. Almost all the experiments described refer to processess occurring in the first and fourth reaction regions of this particular instrument.
EXPERIMENTAL SECTION All data were taken with a custom-built BEQQ mass spectrometer (1-5). The instrument (Figure 1) consists of a Finnigan MAT 212 double focusing mass spectrometer (BE) that has been fitted with a rf-only quadrupole collision region (Q1) and a quadrupole mass analyzer (Q2). Ions selected by the BE section are focused by deceleration lenses onto the entrance aperture of Q1. In Q1, the ions undergo collision-induced dissociation at energies that can be set up to 100 eV. Fragment ions produced in $1 pass into $2 where they are mass analyzed prior to detection by an off-axismultiplier. A similar detector situated immediately after the resolving slit of the BE section allows the instrument to be operated as a conventional high-resolution mass spectrometer. This detector was used for conventional linked scans of B and E (9). Consecutive-reaction experiments utilized a reaction in either the first or second reaction region followed by a subsequent reaction in Q1. Since the translational energy of the ions produced in a collision is mass dependent, the patentials on the deceleration lenses and the rf-only quadrupole bias, and the bias of the mass analyzing quadrupole, are scanntd in concert with B and E. The bias on Q2 is scanned such that all ions passing through Q2 have the same translational energy. These same conditions also apply to all single-reaction experiments occurring in the BE section whose products are passed through the double quadrupole section prior to detection. The magnetic and electric sectors, the rf-only quadrupole supply, the deceleration lenses, and the mass-analysis quadrupole were all supplied with voltages controlled by microprocessors used in the system's distributed processing scheme. Ions were produced in the source by electron impact with 70-eV electrons using an emission current of 1 mA. Sample pressures in the source were typically 6 X torr and the source temperature was typically 150 f 10 "C. All reactions are collisioninduced dissociations unless specifically indicated otherwise. (Metastable ion dissociations, charge transfer reactions, and reactive ion/molecule collisions can also be studied.) Argon collision gas was used, unless otherwise noted, at a collision energy of 3 keV for high-energy collisions and 30 eV for collisions in the rf-only quadrupole. Typical collision gas pressures (indicated) were 2 torr in the X torr in the first reaction region and 2 X collision quadrupole. Signals were output directly t o a recorder. Most of the data shown represent single slow (up to 5 min) scans. Data system developments nearing completion are expected to have the same beneficial effects for this system as noted for so many others in
0 1985 American Chemical Society 0003-2700/85/0357-2918$01.50/0
ANALYTICAL CHEMISTRY, VOL. 57, NO. 14, DECEMBER 1985
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Table 11. New Types of MS/MS Scan Modes Collision Cell RR2 a-slit
-1-
Exitslit Conversion Dynode
1
Entrance slit
-4:1
Ion Source = =
a
_I_
+'-a
Intermediate Detector
---
Needle Collision C e l l d g RR3 Collision Cell R R ~
Reaction Symbol
Reaction
;
I
[__I
Consecutive Neutral Loss
Deceleration Lens RR 4
quadrupole)
J
A%
NUb-
Q 2 (Mass analyzing quadrupole)
I
Final Detector
Selective Parent
NL
Selective Daughter
D
Sequential Parent
P
P
\ o /
Figure 1. Schematic diagram of the hybrid BEQQ instrument showing the four reaction regions (RR1 to RR4). ~-
~
Table I. Scan Types in Mass Spectrometry I Ion Monitoring
Elaborations multtple ion detection (time divided between monitoring of several ions)
NL(D)
o&o
I
i e a
Sequential Daughter
D
D(NL1
i
e
m' (set)
Reaction Monitoring
U
mr-m; (sot)
Elaborations. multiple reaction monitoring (dividing time between different tasks), consecutive reaction monitorinqhonitorirq a linear sequence of reactions).
cm3
Consecutive Reaction Monitoring
i
(ret)
i
D
- Daughter spectrum
P
- Parent
0 -Variable mass
-Fixed mass
spectrum
--.* -Variable reaction
NL- Neutral loss
t
eFixed reaction ~
II Single Criterion Scans Daughter
Parent
Neutral Loss or Gain
Charge Exchange
0
I
[P
Multiple Criterion Scans
Reaciion MonitOring/Daughter Spectrum ifllied paren1 ond grondparenli
Parent/Reaction Monitoring Spectrum i f l x s a daughter
gronaa.ughteri
the past (IO). Mass assignments were checked via duplicate scans and, in a few cases, by using alternative types of scans. Samples were of commercial origin and were used as received.
RESULTS AND DISCUSSION Table I sets out some of the types of scans that can be performed with a mass spectrometer. Because the classification is made on the basis of what is accomplished, rather than the method employed to accomplish it, the information is independent of the type of spectrometer used. Note too, that elaboration has been kept to a minimum in order that
~~
the basic structure of the classification be apparent. The symbolism employed for the scan types (Table I) attempts to provide a convenient summary of a rather complex subject: 0 denotes a fixed mass, 0 denotes a variable, and arrows indicate transitions, with a heavy arrow implying a fixed transition (e.g., neutral fragment m3 selection). There are four elements in the hierarchy shown in Table I: ion monitoring, reaction monitoring, single criterion scans, and multiple criteria scans. Higher members, as well as additional examples o€the several classes, are readily imagined. In all cases m,, m2, and m3 refer to the parent, the daughter species, and the neutral fragment, respectively (or to their mass-to-charge ratios). It is not implied that m2 < m,; viz., associative ion/molecule reactions are not excluded. It is only for convenience that single, positive charges are shown. The multiple criteria scans are discussed and demonstrated for the first time in this paper. Table I1 presents the major new scans discussed in this paper, organizing them in terms of constituent simpler scan types applied in the two separate reaction regions. Note that with the exception of the reaction intermediate scan, each of the scans given in Table I1 falls into one of two broad classes: scans that characterize a given ion (elaborations of simple daughter scans) and those that select for a set of ions (elaborations of parent and neutral loss or gain scans). These two broad classes of MS/MS experiments of course have quite different uses; the former provides information on a single species, the latter selects for a group of ions that have particular properties. Referring back to Table I, it is appropriate to discuss each class of scans briefly. Ion monitoring refers to the well-known experiments in which the abundance of a particular ion is used to monitor for a compound. No spectrum is produced, although the time dependence of the signal may be of interest. In efforts to increase the specificity of the map from the
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ANALYTICAL CHEMISTRY, VOL. 57, NO. 14, DECEMBER 1985 95
Doubly Charged Ion Spectrum, B Scan, 0 Scan Benzene m/z 78 Thiophene m h 54 Furan m/z 68
Sequential Daughter S p e c t r u m B Filter E Filter P S c a n (372+-217+-fragments) Cholestane 0
i
A L o
I
I
78
I
I
I
j; 1 69
I
i
56 I
58 . L
66
I 1
Flgure 2. Pure doubly charged ion mass spectrum of a mixture obtained by a linked scan of B and Q, charge exchange with benzene occurs in a 30-eV collision in the quadrupole collision cell.
compound of interest to ions in the mass spectrum, several ions may be interrogated successively in a multiple ion monitoring experiment. Reaction monitoring, in its simplest form, is a static experiment where (minimally) one reactant and one product of an ionic reaction are specified as a means of characterizing either a reaction, a reactant, or a product. This process is a more specific form of the ion monitoring experiment when applied to the recognition of a particular compound. (The specification of both product and reactant reduces interferences.) If analysis time is distributed between several reactions, then the experiment is termed multiple reaction monitoring. Abrupt variations in field settings can be used to construct an overall experiment from individual (static) reaction monitoring events. Elaboration in the reaction sequence monitored is similarly straightforward; using separation in time, as in Fourier transform mass spectrometry ( 1 1 ) ,or in space as in sector instruments (12-15), one can monitor ml+ m2+ m3+,etc., through a connected series of individual reaction monitoring experiments. In terms of scan types, we consider even sequential reaction monitoring, a form of MS/MS/MS experiment, to belong to the simplest of scan classes, reaction monitoring. I t is a key to the value of this procedure, however, that the experiment monitors a set of sequential reactions, not merely individual unconnected steps. All the reaction monitoring experiments can be classified as zero-order scans based on the dimensionality of the (mass/ abundance) data which they yield. Since the masses are specified, this dimension can be considered to be zero. Single criterion scans are designed to provide the masses and abundances of all ions that satisfy a single condition. They include the well-known parent, daughter, and neutral loss types. A set of ions is transmitted; i.e., one obtains a single mass/abundance listing of all ions that satisfy a particular condition, e.g., all ions that are parents of a specified daughter ion. This is considered to be a first-order scan. In the zero-order reaction monitoring experiment, by contrast, the ions that can satisfy the criteria are known in advance. In both types of experiments ion abundances can show temporal variations, although it is the variation in abundances of different ions that constitutes the spectrum in the single criterion scans. A useful illustration of the single criterion type is the scan for doubly charged ions where they are recognized by mass analysis of their singly charged products resulting from charge exchange. This criterion can be implemented by selecting the reactant and product ions in a linked scan which maintains a 1:2 ratio between the scan rates. In this scan, as in neutral loss scans, two analyzers are simultaneously varied, making the experiments more complex than parent and daughter
- -
57
9; 91
1
Flgure 3. Sequential daughter spectrum (parent and grandparent selection), showing all fragments of cholestane which arise from the molecular ion via 217'.
scans. However, all these experiments must be classified together since just one item of information is fixed in each case. The charge exchange scan, recently implemented using a triple quadrupole spectrometer (16),can be achieved in a variety of ways on the BEQQ, depending on the reaction region chosen and the field(s) used for mass analysis of the parent and daughter ions. Figure 2 illustrates this scan as implemented using the fourth reaction region of the instrument for charge exchange, the magnetic analyzer for parent mass analysis, and the quadrupole mass filter for daughter mass analysis (B scan, E set, Q scan linked to B). The data shown are for a mixture of furan, thiophene, and benzene examined previously using the triple quadrupole instrument (16). Good agreement is achieved between the two methods. Note that doubly charged fragment ions generated in the ion source are observed together with doubly charged molecular ions. The last broad class of scans, multiple criteria scans, is a large class that includes both simpler and more complex types. Two of the simpler examples can be considered as resulting from the combination of the reaction monitoring experiment with the single criterion scan. Symbolically
These combinations both yield first-order spectra, Le., a single set of mass/abundance data. The first case, termed a sequential daughter scan, can be thought of as a daughter spectrum in which both the parent and the grandparent are fixed. (It can also be thought of as a partial granddaughter spectrum, viz., one in which one familial line is interrogated.) The second example, termed the sequential parent scan, is a modified form of parent scan in which both the daughter and granddaughter are fixed. (It can also be considered as a partial grandparent spectrum, viz., one that explores a single parental line.) No other simple combinations of single criterion scans and multiple reaction monitoring exist. Both of the scans just noted are easily implemented using the BEQQ spectrometer. The sequential daughter scan is the only multiple criterion scan that has previously been reported (11-14), and in the form of consecutive metastable ion dissociations, its has a long history (15). In many cases, this scan has been presented as an MS/MS/MS spectrum, a designation which could as well apply to many of the other experiments described here and which we recommend against using.
ANALYTICAL CHEMISTRY, VOL. 57, NO. 14, DECEMBER 1985 193
A
Parent Soectrum ( r n h 931s B k Linked Lim onene mh136 p-Bromophenol m h 172,474 m-ChlaroDhenol m/z 128A30 Nitrobenzene m h 123
Scan
2921
are eliminated if one adds the criterion that further loss of a fragment of 28 dalton must follow if m / z 93 is to be recognized as the phenoxy cation. (The terpene hydrocarbon limonene shows m/z 93 as the third most abundant ion in its mass spectrum.) The particular example illustrates the fact that the more complex scans may be effective alternatives to exact mass measurements. A parent spectrum with exact mass selection of the fragment C6H60+might be used instead of the selective parent scan to obtain the same information. The resolution in the sequential parent scan can be seen (Figure 4) to mirror that obtained in the parent scan itself. The next three types of scans (Table IJ can all be considered to arise by combining neutral loss (gain) scans with the single criterion scans, viz., with neutral loss, parent, and daughter scans. There are just three combinations which give first-order spectra, i.e., a single set of mass/abundance data. These are consecutive neutral loss, neutral loss followed by a parent scan, and a daughter spectrum followed by a neutral loss. These scans are termed consecutive neutral loss, selective neutral loss, and selective daughter. The names are chosen to reflect what seem to be important potential applications. For example, the selective daughter scan seems more likely to be used to select a subset of daughter ions than to be used as a modified type of neutral loss spectrum although such uses can be imagined. The scan designated as
I172
''&' II
Figure 4. Parent spectrum compared with sequential parent spectrum (daughter and granddaughter selection) for mixture shown. All ions in the parent spectrum that give rise to the granddaughter fragment at m l z 65' are detected in the sequential parent scan.
It is this type of ambiguity which argues the need for the more detailed categorization used here. Figure 3 illustrates the sequential daughter spectrum in the case of the transition 372' 217' in cholestane. This double collision-induced dissociation experiment employs a kiloelectronvolt collision in the first field free region of the BEQQ spectrometer to generate m/z 217, which is in turn fragmented in a low-energy collision. The sequential daughter spectrum is recorded by scanning Q with B set and E set to monitor the transition 372+ 217' in the first reaction region. It is of interest to compare the data in Figure 3 with the daughter spectra of both 217' and 372+. The two spectra of 217' are remarkably similar with the major differences being the addition of ions at m / z 175, 189, and 203 in the normal daughter spectrum. The daughter spectrum of 372' is quite different in that many of the fragments of mass greater than 217', such as 218+, 262', and 357', further fragment to give lower mass ions at m/z 207,203,175, 148, 136, 122,108,106,82, 71, etc. that are filtered out by the sequential daughter scan. Figure 4 illustrates the sequential parent spectrum, which is the counterpart of the sequential daughter spectrum just discussed. The sequential parent scan is achieved by setting the quadrupole mass analyzer to pass a specified granddaughter fragment ion, while scanning B and E in a conventional linked scan parent mode (B2/E= constant). The offset between the fragment ion passed by the sectors, and that for which the quadrupole is set, makes this a selective parent ion. In the case illustrated, all parents of 93' are recorded (upper spectrum) in an attempt to identify compounds in the mixture that contain or can rearrange to yield the phenoxy structure (viz., phenols, esters of phenol, nitrobenzenes, etc.). Among the ions so identified is the molecular ion ( m / z 136) and a fragment ion ( m / z 121) of limonene. These false positives
-
-+
could be named as a modified type of parent or neutral loss spectrum. The selective parent designation has been chosen in part to increase the symmetry of the overall system of nomenclature (Table 11). The consecutive neutral loss scan typifies the power of these new experiments. The value of neutral loss scans in selecting for particular types of constituents of complex mixtures has led to its use in such areas as fuel science (17-19) and drug metabolite monitoring (20,21). On the other hand, for complex mixtures, false positives are to be expected. Fortunately they can be eliminated or greatly reduced by use of these more selective scans. It should also be possible to select a consecutive reaction typical of a class of compounds with minimal chance of false negatives provided the ion chemistry of the system is well-understood. In the consecutive neutral loss scan a subset of ions is characterized from a particular set by the ability of these ions to lose a neutral m3, and by the ability of the resulting daughter ion to lose a second neutral mi. The characterization (for example, of peptides containing particular terminal and penultimate amino acids) depends on the sequential loss of m3 and m i . Figure 5 illustrates the consecutive neutral loss spectrum (30 followed by 28) of a mixture of aromatic compounds and compares it to the neutral loss 30 spectrum. The example is chosen to illustrate the fact that loss of 30 is an appropriate but not a sufficient criterion for the identification of nitroaromatic compounds. In the presence of certain methoxy compounds, the criterion yields false positives because loss of H2CO is not distinguished from loss of NO (22-24). While this distinction could be made in other ways, it is well-known that the loss of NO from aromatic compounds yields phenoxy-type cations (Figure 3) and that CO loss is a dominant fragmentation mode of these ions (25, 26). Hence, if one specifies the sequence of reactions in which elimination of 30 daltons is followed by loss of 28, the specificity of detection of nitroaromatric compounds should increase. Figure 5 demonstrates this. Unlike the MS/MS scans discussed so far, this experiment requires simultaneous scans of B, E, and Q. Specifically B and E are scanned to acquire a conventional neutral loss linked scan but Q is offset in mass from the
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ANALYTICAL CHEMISTRY, VOL. 57, NO. 14, DECEMBER 1985 108
Neutral Loss Spectrum (301 82/E2(E-Eo)Scan Anisole m/z 108 m-Toluidine m/z107 Nitrobenzene m/z 123 m-Chloroanisole m h 142/144 Fluoronitrobenzene m/z 141
Daughter Spectrum (m/z 2061: W E Linked Scan 6,7-Oimethoxycoumorin m h 206
'i"
'i
123
109
113
122
Consecutive Neutral Loss (30 followed by 28)
Sr t r u m : B?E~(E-E,)SC~~, Q Scan 123
1
Selective Dauqhter Spectrum' WE Linked Scan,QOffs
91
(Daughter 206+/Neutral Loss 281 163
I
Flgure 5. Neutral loss spectrum compared with a consecutive neutral loss spectrum for a mixture of aromatic compounds. I n the latter scan, only those components that follow the reactlon sequence, neutral loss of 30 followed by neutral loss of 28, are detected.
fragment ion selected for by B and E and this offset is held constant as B, E, and Q scan. While the scan just discussed is somewhat analogous to the sequential reaction monitoring experiment, as indicated by their symbols (0-,3-bOVS
.-.*.+.)
the differences are remarkable. The double neutral loss scan displays all ions of whatever mass and origin which satisfy the two criteria for m3, and as such it is primarily of use in examining mixtures. The sequential reaction monitoring experiment is set up with no uncertainties with respect to mass; the information obtained corresponds to a defined reaction sequence usually for a single compound (except for fortuitous mass coincidences). The combinations of neutral loss (gain) with parent and daughter scans, viz., the selective daughter and selective parent scans, can now be discussed. Figure 6 displays the daughter spectrum of the molecular ion (m/z 206) of 6,7-dimethoxycoumarin as well as two different selective daughter spectra. The latter spectra were obtained with a B/E linked scan with the mass analyzing quadrupole scanned synchronously with the daughter mass, but offset from it by a fixed amount. These spectra can be used to select a subgroup of fragment ions, e.g., those with a methyl group or incipient methyl group (lower scan, Figure 6). It is easy to imagine such spectra being used to characterize those fragment ions which incorporate labeling or other molecular modification sites. The possible application of this scan will be in experiments such as sequencing of biomolecules, where a simple daughter spectrum is complicated by nonsequence ions, further fragmentation of sequence ions, and other interferences. In such cases, considerable advantage would attach to a daughter spectrum which is selective only for a particular class of sequence ions,
Flgure 6.
Daughter spectrum compared with selective daughter spectra of molecular ion of 6,7-dlmethoxycoumarin. Only those jaughter ions that further fragment by loss of 28 (center) and 15 :bottom) are detected in the selective daughter scan.
?.g., those which lose CO from the acyl cleavage product of 3 peptide (27). Figure 7 displays how selective parent spectra can be used 1to greatly simplify neutral loss spectra. These scans serve the Liame purpose as consecutive neutral loss scans, but achieve iit by specifying a granddaughter fragment resulting from a Iiubsequent dissociation of all ions which undergo an initial 1reaction losing a preselected neutral fragment. This type of Lipectrum seems to be particularly promising when one desires 1;o search both for a particular functionality and for a par1;icular skeletal structure. The figure shows a set of methyl (:ompounds that can be recognized by neutral loss of a neutral 1Yagment of mass 15 dalton. Since methylated aromatic (:ompounds almost always display fragment ions of m / z 65 I n their electron impact mass spectra, a scan which specifies i;hat a neutral of 15 dalton be lost and that 65' be generated f%omthe initial fragment (bottom, Figure 7) shows responses f'or members of this class of compounds (represented here by f?thylbenzene, anisole, 2-methyl-5-ethylpyridine, and thio-
ANALYTICAL CHEMISTRY, VOL. 57, NO. 14, DECEMBER 1985 Daughter Spectrum B Filter E
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Scan
Hexochlorophene Molecular Ian (m/z408)
Anisole m h 108
1
Selective Parent Spectrum: B?E'(E-b) (Neutral Loss 15/Parent 5 5 * )
Scan,
Q Filter
Daughter Spectrums B F i l t e r EQ Scan
198
Hexachlorophene Molecular Ion (m/z 408) 0
211
196
I
Selective Parent Spectrum I
1' '
S2/E2(E-Eo)Scan, Q Filter (Neutrol LosslS/Parent 65+)
I
124
1
Flgure 7. Neutral loss spectrum compared with selective parent spectra of the mixture shown. Selective parent spectra recognize aliphatic (center) and aromatic (bottom) methyl compounds.
anisole). The aliphatic methylated compounds are recognizable by specifying m / z 55 as the characteristic fragment ion. The formal consideration of types of mass spectrometry experiments can conveniently be terminated by considering the scans that might result from juxtaposing parent and daughter spectra. The sequence parentldaughter does not give a simple spectrum, i.e., it is higher than first order in the sense used in this paper. For this reason it will not be considered further.
By contrast, the daughterlparent combination results in a single set of ion/abundance values. This scan is termed a reaction intermediate scan. It can be seen from the symbol
200
Flgure 8. Linked scan for improved performance in MIKES, showing enhanced resolution over conventional MIKES (daughter) spectrum of 408' derived from hexachlorophene (B filter, E scan, Q scan). I n this spectrum the 408' ion underwent metastable dissociation in the second reaction region.
that this scan represents all those ions that occur as intermediates between a specified parent and a specified daughter. (Their relationship to each other is not specified by this experiment alone; i.e., they may be sequential or parallel intermediates.) This type of scan, as is the case for all those discussed here, can be implemented using the BEQQ instrument. Examples and methodology will be presented in detail elsewhere (28). Intermediates with lifetimes on the order of the mass spectrometer flight time should be among the interesting applications of this scan type. We complete this discussion by emphasizing that it is possible to improve performance in even the simpler scan types by using appropriate instrumentation. However, this type of experiment must not be confused with the new scan types, which are summarized in Table I1 and are the focus of this paper. For example, the well-known MIKES scan is a type of daughter scan implemented in a particular way (B filter, E scan). Improved performance is possible by using a BEQQ hybrid and scanning Q in tandem with E as an additional means of daughter ion analysis. A comparable experiment has been done on an EQ instrument (29),but the mass-analyzed EQ linked scan is demonstrated, for the first time, in Figure 8. Without the supplemental quadrupole analysis, the 408' daughter ion spectrum shows unresolved doublets in place of the rich multiplets revealed in the improved daughter scan. Similar improvements in other simple scans are also possible, including removal of certain artifacts from conventional B/E and related linked scans. This topic will be treated elsewhere.
CONCLUSION In spite of the scope of the preceding discussion, all the experiments described fall into a single general class: they
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monitor processes in which specific changes in mass-to-charge ratios of ions occur. A second equally broad experiment is the analog of optical absorption experiments; one can monitor unconverted reactant (together with products that have the same mass-to-charge ratio as the reactant) rather than any particular product or group of products. This experiment yields a spectrum of ions which survive the experimental probe (30-32). The advantage of this approach is that it represents all loss (reaction) mechanisms cumulatively. The condition m3 = 0 allows one to combine these processes with those already given in Table I and so allows a still more general classification of MS/MS processes. A number of completely new types of MS experiments have been described in this paper. These experiments are not simply methods of improving the quality of the information already available by other techniques; rather, they provide new information. They represent easily implemented experments (given the appropriate instrumentation) of greater information content than previously available. The BEQQ geometry insrument is uniquely suited to provide these new types of scans. The EBQQ hybrid has similar capabilities but has drawbacks for some of the scans described in this paper. Fourier transform instruments, which separate ions in time rather than in space in order to perform MS/MS, have severe limitations for the type of work discussed here. Even simple parent spectra must be reconstructed from the full set of daughter spectra so sequences of scans will be difficult to implement except for the multiple daughter ion sequence, in which FTMS is known to be uniquely powerful (33, 34). The scans described here are the first new types of scan modes described since the discovery of the neutral loss scan (35-37) *
ACKNOWLEDGMENT We thank Jon Amy for contributions which underlie this project.
LITERATURE CITED Schoen, A. E.; Dobbersteln. P.; Amy, J. W.; Ciupek, J. D.; Cooks, R. G. Presented at the 31st Annual Conference on Mass Spectrometry and Allied Toplcs, Boston, MA, May 8-13, 1983. Schoen, A. E.; Amy, J. W.; Ciupek, J. D.; Cooks, R. G.; Dobberstein, P.; Jung, G. Int. J . Mass Spectrom. Ion Proc. 1985, 65, 125-140. Ciupek;J. D.; Amy, J. W.; Cooks, R. G.: Schoen, A. E. Int. J . Mass Spectrom. Ion Proc. 1985, 6 5 , 141-157. Dielmann, G.; Pesch, R.; Schoen, A. E. Presented at the Pittsburgh Conference and Exposition on Analytical Chemistry and Applied Spec-
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RECEIVED for review April 1,1985. Accepted August 5,1985. This work was supported by the National Science Foundation (CHE-8408258).
