Transcript Mass Spectrometry - Villanova University

Mass Spectrometry and Related
Techniques 3
Lecture Date: March 11th, 2013
Applications of Mass Spectrometry
 Interpretation of mass spectra is the key to most
applications of the technique
 Information contained in a mass spectrum:
– Molecular weight (via exact or mono-isotopic mass). Usually
obtained though a suitably accurate measurement of:
 M+• (the molecular ion, an odd-electron species)
 [M+H]+ and [M-H]- (the protonated/de-protonated molecule, an
even-electron species)
 In some techniques, can be confirmed by [M+Na]+, [M+K]+,
[M+NH4]+, dimers, trimers, and other adducts, etc…
–
–
–
–
Molecular formula
Ionization energies
Isotopic incorporation (ex. 13C, 14C, 2H, 3H…)
Fragmentation and ion stability
Quasi-equilibrium Theory
 Once we make an ion, what happens to it?
 In EI, and similar
techniques: the
ionizing electron has
little mass and high
KE, so it barely
moves the molecule
that it hits but leaves
it in a higher
rotational/vibrational
state.
 Ionization energies
can sometimes be
determined from ion
intensities.
Diagram from Strobel and Heineman, Chemical Instrumentation, A
Systematic Approach, Wiley, 1989.
Molecular Structural Analysis: Fragmentation
 Fragmentation can also be used to determine structure
O
– common fragmentation pathways and
rearrangements can be predicted in many cases
Cl
 General rules:
-
-
-
p-chloro-benzophenone
More stable
carbocations are more
stable fragments (ex.
tertiary carbocations are
more stable than
primary)
Resonance can stabilize
fragments, ex. allylic
carbocations and
benzyl/tropylium ions
Loss of small, neutral,
stable molecules is
favored
Figure from R. M. Silverstein, Spectrometric Identification of Organic Compounds, 6th Ed., Wiley, 1998.
Molecular Structural Analysis: Fragmentation
 A large number of gas-phase fragmentation reactions commonly
observed in MS analysis. Some examples:
H
OH
H
H
H
OH2
H
-H2O
H
limonene
H
 Rearrangements also occur (the McLafferty rearrangement is shown):
See R. M. Silverstein, Spectrometric Identification of Organic Compounds, 6th Ed., Wiley, 1998.
Molecular Structural Analysis: Adducts
 Typical adducts observed in MS:
–
–
–
–
–
[M+H]+
[M+NH4]+
[M+Na]+
[M+K]+
etc…
 So for a molecular ion with mwt = 400
– [M+H]+ = 401, [M + Na]+ = 423, etc…
 Dimers and other molecular adducts are also observed, e.g.:
– [2M+H]+ = 801
– [2M+Na]+ = 823
– etc…
See R. M. Silverstein, Spectrometric Identification of Organic Compounds, 6th Ed., Wiley, 1998.
Molecular Structural Analysis: Isotope Patterns
 Isotope patterns can be used to
M
(100%)
determine molecular structure
– Example: the well-known methods of
calculating (M+1) and (M+2) intensities
– Especially useful for detecting chlorine,
bromine, sulfur, silicon and many other
elements with characteristic profiles
M+1
(19.28%)
 Isotope patterns can also be used to
M+2
(33.99%)
extract out “isotope incorporation
profiles” for labeled compounds
– Examples: 13C, 14C, 2H, 3H-labeled
molecules for metabolism studies
– Applications in isotope chemistry include
the detection of stable and radioactive
isotopes in synthetic products and in
nuclear chemistry.
M+3
(6.21%)
215
220
m/z
O
Cl
p-chloro-benzophenone
Molecular Structural Analysis: Accurate Mass
 Nuclide masses are not integers.
Example: Four things
that weigh “28” amu:
– CO, 27.9949
– 14N2, 28.0062
– CH2N, 28.0187
– C2H4, 28.0312
 m/z measurements to four decimal places or higher are
needed
 Accurate mass analysis is often used as a final
confirmation of structure, or for unravelling complex
fragmentation
Molecular Structural Analysis: Mass Defects
Mass Defect (Da)
0.02
2H
1H
0.01
13C
14N
15N
Atomic
Mass Defects
(All Different)
0
12C
-0.01
-0.02
-0.03
-0.04
16O
Mass Defect =
Atom Mass – Nearest Integer
Every CcHhNnOoSs mass
is unique!
0 1 2 3 4
5 6 7 8
31P
32S
9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34
Mass (Dalton)
Picture courtesy Prof. Alan Marshall, FSU/NHMFL
Molecular Structural Analysis: MS-MS, and MSn
 Step 1 – mass selection of an ion formed in the source
 Step 2 – dissociation of the parent ion via collisions
 Step 3 – mass analysis of the dissociated “daughter” ions
 Step 4 – repeat…
+
+
+
+ + +
+ +
Mass
Analyzer 1
+
+
+
+ + +
+ +
Collisions
Mass Analyzer
and Collision
Chamber
Mass
Analyzer 2
More About MSn Systems
 Tandem-in-space
– Means that the mass selection and fragmentation occur in
different physical locations within the spectrometer.
– Examples: Triple-quad (QQQ), in which…
+
+
+
+ + +
+
+
Mass
Analyzer 1
Collisions
Mass
Analyzer 2
 Tandem-in-time
– Means that the mass selection and fragmentation occur in the
same part of the MS but at different times
– Example: ion traps
Dissociation and Controlled Fragmentation in MSn
 Collisionally-Induced Dissociation (CID)
– Also known as collisionally-activated dissociation (CAD), CID is the
principal ion-dissociation method for MSn. In CID, stable ions are
fragmented by collisions with neutral gas atoms/molecules
 CID uses low-pressure He or Ar gas
– Ion traps typically use 10-3 torr of He
– Triple-quadrupole systems typically use 10-6 torr of Ar
– Also can use N2, Xe, etc…
 Other methods:
– Photo-induced dissociation
 IRMPD (IR multiphoton dissociation) – via IR lasers
 BIRD (blackbody infrared radiative dissociation)
– Surface-induced dissociation (SID)
– Electron-capture dissociation (ECD)
– Electron-transfer dissociation (ETD) – uses a molecular anion to
deliver charge
L. Sleno and D. A. Volmer, “Ion activation methods for tandem mass spectrometry”, J. Mass Spectrom., 2004, 39, 1091-1112.
Collisionally-Induced Dissociation
 Low-energy CID – ions traveling with typical KE of <100
eV.
– Ions excited to a higher vibrational state, ion-target complex has
a lifetime
 High-energy CID – ions travelling with typical KE > 1 keV
– Ions excited to higher electronic states, no detectable ion-target
complex
 CID occurs via a two-step mechanism:
Step 1. An endothermic activation step to form an M+ ion that is
internally excited (usually to a higher vibrational state)
Step 2. An exothermic unimolecular decomposition to a fragment
ion and a neutral.
For more information about CID, see:
L. Sleno and D. A. Volmer, “Ion activation methods for tandem mass spectrometry”, J. Mass Spectrom., 2004, 39, 1091-1112.
K. R. Jennings, Int. J. Mass Spectrom. Ion Phys., 1968, 1, 227.
F. W. McLafferty, et al., “Collisional Activation Spectra of Organic Ions”, J. Am. Chem. Soc., 1973, 95, 2120-2129.
K. Levsen and H. Schwarz, “Gas-phase Chemistry of Collisionally-activated Ions”, Mass Spectrom. Rev., 1983, 2, 77-148.
S. A. McLuckey, “Principles of Collisional Activation in Analytical Mass Spectrometry”, J. Am. Soc. Mass Spectrom., 1992, 3, 599-614.
Molecular Structural Analysis with MSn
 CID and MSn opens up a range of possiblities for MS
Scan Modes
– Precursor ion scans: keep MS2 constant, scan MS1
– Product ion scans: keep MS1 constant, scan MS2
– Neutral loss scans: scan MS1 and MS2 “in sync”, offset by the
difference (neutral) of interest (ex. set MS2 to follow MS1 by 32
Da).
– Selected reaction monitoring: hold MS1 and MS2 constant
(observe a selected fragmentation)
Mass
Analyzer 1
Collisions
Mass
Analyzer 2
Applications of MSn Experiments
 A short list of applications:
MSn studies of drug
metabolism, environmental samples,
 Especially useful in drug metabolism because key
“pieces” of drugs can be selected via their product
(daughter) ions or their neutral loss characteristics
 MSn is applicable to any analytical situation where
complex, overlapping spectra are detected and need to be
interpreted
For more information about MS applications in drug metabolism, see:
R. J. Perchalski, R. A. Yost and B. J. Wilder, Anal. Chem., 1982, 54, 1466-1471.
M. S. Lee and R. A. Yost, Biomed. Environ. Mass Spectrom., 1988, 15, 193-204.
Applications of MSn Experiments
 Example: Structural analysis of linear



alkylbenzylsulfonates - a common
anionic surfactant that can be a soil
pollutant
Can be monitored in soil by LC-ESI-MSn
Samples extracted with methanol,
concentrated with SPE
Bruker Esquire 3000 ITMS, negative ion
mode (compounds are negatively
charged) in this mobile phase:
water/methanol/tributylamine/NH4COOCH3
 m/z = 183 obtained from CID MS-MS of

all chain lengths as a characteristic ion
m/z = 119 obtained from CID MS-MS-MS
of m/z = 183 by loss of SO2
V. Andreu and Y. Pico, Anal. Chem., 2004, 76, 2878-2885
Molecular MS Applications: Environmental Science
 A compound was discovered in smoke derived
from burning plant material that increases
germination of a range of plant species that
typically follow forest fires.
 The compound is 3-methyl-2H-furo[2,3-c]pyran2-one, and it was synthesized after being
isolated and analyzed by MS and NMR
O
O
O
CH3
C8H6O3
Exact Mass: 150.03
Mol. Wt.: 150.13
m/e: 150.03 (100.0%), 151.04 (8.8%)
C, 64.00; H, 4.03; O, 31.97
GC-MS (EI) Data:
 GC-MS was able to detect this butenolide at low
levels in “smoke waters”
 The compound is stable at higher temperatures,
and is active at 1 ppm to 100 ppt levels. It is
derived from the combustion of cellulose.
G. R. Flemmatti, Science., 305, 977 (2004)
m/z = 150 (100%, M+)
m/z = 122 (25%, loss of CO)
m/z = 121 (71%)
m/z = 66 (14%)
m/z = 65 (16%)
Molecular MS Applications: Proteomics
 Proteome: The group of proteins related to a cell type (with a certain


genome) under certain conditions (often forced on the cell)
Genome: The complete DNA sequence of a set of chromosomes.
Proteomics: The analysis of native and post-translationally modified
proteins to characterize complex biological systems. There are at
least three “types” of proteomics:
– Profiling Proteomics: Identify the proteins in a biological sample (or
differences between proteins in multiple samples)
– Functional Proteomics: Determine protein functions by finding specific
functional groups or interactions
– Structural Proteomics: Determine the tertiary structure of proteins and
their complexes (e.g. using H/D exchange).
 Sequencing: The analysis of primary structure of an oligomer (e.g. a
protein) by bottom-up (chemical digestion, then MS) or top-down (do it
all via selective fragmentation in the MS)
D. Figeys, Anal. Chem., 75, 2891-2905 (2003)
Molecular MS Applications: Proteomics
 MS is historically used for profiling proteomics but has
greatly increasing applications to other areas.
 MS can be used in conjunction with gel electrophoresis
techniques (2D GE, SDS-PAGE, etc…) or with
separations (LC)
 MS can be used to study post-translational modifications
of proteins (e.g. phosphorylation, glycosylation)
R. Aebersold and D. R. Goodlett, “Mass Spectrometry in Proteomics”, Chem. Rev., 2001, 101, 269-295.
Molecular MS Applications: Proteomics
 “Peptide mass mapping”:


used to ID proteins by
comparison to a database
(bottom-up proteomics).
Accurate mass methods
(single MS stage) are usually
used, following digestion by
an enzyme (e.g. trypsin) that
“chews up” the peptide into
fragments.
The better the mass
accuracy, the less chance of
isobaric (same mass)
interferences.
R. Aebersold and D. R. Goodlett, “Mass Spectrometry in Proteomics”, Chem. Rev., 2001, 101, 269-295.
Molecular MS Applications: Proteomics
 Sequence-specific peptide MS: usually


done with MSn methods involving CID
Produce MS data that contains signals
for each amino acid in the protein.
Results in complex spectra, which can
be handled in different ways…
1. Searched against DB
2. Directly analyzed (top down)
3. Use chemical tools to ID fragments
(bottom up)
1. Edman degradation
2. H2O trypsin proteolysis
3. Methyl esterification
R. Aebersold and D. R. Goodlett, “Mass Spectrometry in Proteomics”, Chem. Rev., 2001, 101, 269-295.
MS Methods for Surface Analysis
 Secondary-ion MS (SIMS) in
surface analysis
Ions: Ar+, Cs+, N2+, O2+
– Secondary analyte ions are
5-20 keV
produced by impact from a
primary ion
Ions
– Can depth-profile (sputtering and
ionization)
– Typical analysis depths – 10-30
Å, with lateral resolution of < 1
um
 TOF-SIMS – why is this
combination so special?
– SIMS works well with delayedextraction methods
– Pulsed ion guns (time-resolved
pulses followed by drifts)
To
Mass
Analyzer
Sputtered
Atoms
Surface Analysis: TOF-SIMS
 Micropatterning of

biomolecules on a
substrate: potential
applications for
biosensors
Example: a
surface-derivatized
polymer (PET, with
COOH groups) is
used to couple
biological ligands:
– BiotinSteptavidin
Figure from Z. Yang, et al. Langmuir 2000, 16, 7482-7492
Mass Spectrometers as GC/LC Detectors
 MS is increasingly used as a routine chromatography detector
(especially in GC and LC)
 Two modes:
• Single-ion monitoring (SIM): observe 1-4 ions selectively –
•
improved signal-to-noise for ions of interest
Total ion current (TIC): sum of all ions – can be noisy but also
captures potential unknown m/z ratios
 In these cases, the basic MS system (usually simple quadrupoles with
limited resolution and mass ranges) is known as a “massspectrometric detector” or MSD
D. Figeys, Anal. Chem., 75, 2891-2905 (2003)
Ion Suppression
 Ion suppression (one ion preferentially ionizing to the detriment of
another) can cause quantitative issues in LC-MS analyses when
multiple compounds elute simultaneously.
 Complex biological matrices (e.g. in clinical samples) often lead to ion
suppression.
 Can be avoiding by matching standards and matrices to the analyte
Niesson et al., Mass Spectrometry Reviews, 2006, 25, 881– 899
Elemental Analysis with ICP-MS
 ICP-MS is similar to ICP-AES – the sample is vaporized

and desolvated, and vaporized atoms are then ionized
Isobaric interferences from plasma or matrix components
Diagram from Agilent Instruments Promotional Literature.
Advantages of ICP-MS
 Typical sensitivity: 0.1-1 ug/L (ng/mL) in solution
 Many elements at once (~50 at a time)
 Different interferences than ICP-OES
 Can achieve ppt (ng/L) detection limits for rare earths
and actinides
Metallic Ion Speciation using HPLC-ICPMS
• What is an metallic ion species? It is the valence state of a metal (or the
organometallic form)
• Example:
• chromium +3 (Cr+3) - essential nutrient
• chromium +6 (Cr+6) – highly toxic (Cr+6 is the contaminant made famous by
Erin Brockovich in the groundwater of Hinckley, CA)
• HPLC/ICP-MS specifically detects Cr+6 with an LOD of 0.06 ng/mL
• Sample prep – addition of “harsh” chemicals can alter equilibrium, and
alter the concentration of species. Example - Dissolution of Cr samples
in hot acid converts Cr+6 to Cr+3
• Typical HPLC flow rates 0.1 – 0.5 mL/min – can extinguish plasma if too
high.
AMS: Accelerator Mass Spectrometry
• We know that MS can determine isotope ratios. But what happens if
we want to determine isotope ratios when the isotopes differ in quantity
by a factor of 10-5 to 10-9 ?
• AMS offers isotope quantification at attomole (10-18 mole) sensitivity
• Numerous applications to “long-lived” radioisotopes, which are a
challenge to detect by decay counting methods
• Features:
• High-efficiency negative ion source (cesium sputter)
• Tandem electrostatic acceleration
• High energy ions detected by counting in a gas ionization detector (fast ion
causes gas to ionize itself, emit x-ray, which is detected.)
• The AMS design is essentially a sector system with an accelerator and a
“stripper” (argon gas unit – to destroy molecular ions)
For reviews of AMS, see:
K. W. Turteltaub and J. S. Vogel, “Bioanalytical Applications of Accelerator Mass Spectrometry for Pharmaceutical Research”,
Current Pharmaceutical Design, 2000, 6, 991-1007.
J. S. Vogel, et al., “Accelerator Mass Spectrometry”, Anal. Chem., 1995, 353A-359A.
AMS: Basic Instrument Design and Operation
•
•
•
Negative ions are created (usually
from a solid sample)
These ions are accelerated (MeV)
by ever increasing positive
potentials
The ions are rammed into a carbon
sheet, creating positive ions (i.e. the
charge is “reversed”)
•
Velocity selector
The ions then pass into a high
resolution double-focusing
sector instrument allows e.g.
separation of 14C and 14N
•
•
University of Arizona
Includes pre-selection of a
narrow KE spread (velocity
selector)
The AMS system at the
University of Arizona is shown
AMS: Radiocarbon Dating
• The 14C isotope:
•
•
•
•
Half-life (1/2): 5730 years
Abundance: 1 part per trillion
Produced in the atmosphere from cosmic rays, 14CO2
All terrestrial life maintains a constant 14C level (although ocean life and
“land” life differ)
• When a plant or animal dies, its uptake of 14C stops, and the
equilibrated levels in its tissue begins to decay.
• If the remaining amount of 14C can be measured, the age of the plant or
animal can be estimated.
• In AMS, the ratio of 13C to 14C is measured (sequentially, with two
different detectors) and ages can be determined by comparison to
calibrated references
• Prepared isotope ratios are used to calibrate the ratio
• Samples of known age are used to calibrate the dating method
AMS: Other Applications
• Other applications of AMS:
• Pharmaceuticals (ADME – absorption, distribution, metabolism,
excretion) – using “microdoses” in humans even before tox studies!
• Biochemical pathways
Element
Isotope
Half life
(years)
Sensitivity
(parts per 1015)
Hydrogen
3H
12.3
0.1
Beryllium
10Be
1.6 x 106
5
Carbon
14C
5730
2
Aluminum
26Al
720,000
3
Chlorine
36Cl
300,000
5
Calcium
41Ca
105,000
2
Iodine
129I
16 x 106
10
K. W. Turteltaub and J. S. Vogel, “Bioanalytical Applications of AMS for Pharmaceutical Research”, Cur. Pharm. Design, 2000, 6, 991-1007.
J. S. Vogel, et al., “Accelerator Mass Spectrometry”, Anal. Chem., 1995, 353A-359A.
See also C&E News, July 11, 2005, pg. 28.
IMS: Ion Mobility Spectrometry
• In IMS:
• Sample vapor introduced by thermal desorption or other techniques
• The vapors from the above are ionized using 63Ni (~10 mCi sample) to
produce molecular ions or clusters of molecular ions
• An electronic shutter gates ions into a drift tube with a ~200 V/cm potential
• Ions drift down the tube, colliding with neutral gas molecules (~760 torr)
• Larger ions have longer drift times because of their larger cross-sections
Ion Source
Drift Tube
Detector
• The ions strike a detector (can be a MS), and are identified by flight time
• Typical drift times 3-50 ms, typical time resolution +/- 0.040 ms
Diagram from G. W. Eiceman and J. A. Stone, Anal. Chem., 76, 390A-397A (2004).
G. W. Eiceman, Critical Rev. Anal. Chem., 22, 471-489 (1991).
D. C. Collins and M. L. Lee, “Developments in ion mobility spectrometry – mass spectrometry”, Anal. Bioanal. Chem., 372, 66-73 (2002).
IMS: Theory
•
In IMS, larger ions have longer drift times because of their
larger cross-sections
•
The difference in drift time is proportional to the electric field
strength and a mobility (kim):
vd  kim E
(for E  1000 V cm 1 )
Where:
vd is the average velocity of an ion (cm s-1)
kim is the ion mobility constant (cm2 V-1 s-1)
E is the applied electric field strength (V cm-1)
•
The Mason-Schump equation predicts kim, which is a
function of temperature and pressure as well as other
factors:
 ze  2 1/ 2  1 

 
kim  163  
 N 0  kT    D 
z is the charge of the ion and e is the electron charge (1.602x10-19 C)
k is Boltzmann’s constant and T is the temperature (K)
 is the reduced mass of the ion-drift gas pair
D is the ion-neutral cross-section area (=d2 for rigid-sphere
collisions where d is the sum of the ion and drift-gas radii)
G. W. Eiceman, Critical Rev. Anal. Chem., 22, 471-489 (1991).
D. C. Collins and M. L. Lee, “Developments in ion mobility spectrometry – mass spectrometry”, Anal. Bioanal. Chem., 372, 66-73 (2002).
IMS: Ion Mobility Spectrometer Design
•
•
Advantages
• No vacuum pumps needed
• Can be operated at room temperature, with air as a drift gas
• Small enclosures (handheld) are possible – drift tubes can be ~6
cm long and 1 cm in diameter
Disadvantages
• Flight times must not overlap and must be carefully calibrated
• Low information content
Diagram from G. W. Eiceman and J. A. Stone, Anal. Chem., 76, 390A-397A (2004).
IMS: Applications
• Airport Security
• IMS is used to detect explosives through a luggage checking system - more
than 10,000 units are in use at airports worldwide
• When a piece of luggage is searched by hand, often after a suspicious Xray image is observed, swabs can be taken and run through an IMS
spectrometer to detect many common explosives
• Example: IMS can easily detect RDX (a.k.a. hexogen, cyclonite). This
explosive was used in several recent terrorist attacks in Russia (August
2004) - see C&E News, 6-Sep-2004, pg. 15
• Military/Defense
• IMS can be used to
detect common
chemical weapons more than 50,000
systems (many
handheld) are deployed
with military units
worldwide, as of 2004
Picture and Data from G. W. Eiceman and J. A. Stone, Anal. Chem., 76, 390A-397A (2004).
IMS: Applications
• Handheld units
• Early units weighed ~1.6 kg,
were used extensively in the
1991 Gulf War to test for
nerve and blister agents
• Newer units weigh less than
0.5 kg
• The radioactive source has
been replaced with a corona
discharge ion source – can
run for up to 40 hours
continuously on a single
battery charge
Photo and Data from G. W. Eiceman and J. A. Stone, Anal. Chem., 76, 390A-397A (2004).
IMS: Dopants and Reactant Ions
• Proton affinity determines ionization (especially in
63Ni sources)
• Reactant ions are used to achieve selectivity
• The analyte ion actually forms a pair with
whatever suitable reactant ion is in the drift gas
• Examples:
•
•
•
•
Water (in air)  the hydrated proton [H2O]nH+
Acetone (Ac)  AcH+ and Ac2H+
Ammonia  [H2O]nNH4+
Methylene chloride  Cl- (by dissociative e- capture)
G. W. Eiceman and J. A. Stone, Anal. Chem., 76, 390A-397A (2004).
IMS Example
• DMMP - Dimethyl methylphosphonate (Used to simulate
organophosphorus nerve agents like sarin, tabun, and
soman safely)
• Using acetone as a reagent gas
• The resulting mobility spectrum:
Figure from G. W. Eiceman and J. A. Stone, Anal. Chem., 76, 390A-397A (2004).
IMS: Pharma Applications
• IMS can be used to
detect pharmaceuticals
(small organics)
• Can outperform HPLC
• Smith’s detection
IONSCAN
• Disadvantage: the
drug (or impurity)
needs to be ionized – it
can decompose during
this process, leading to
multiple ions
Figures from Y. Tan and R. DeBono, Today’s Chemist at Work, 15-16 (November 2004). www.tcawonline.org
Hyphenated Ion Methods
 Note – here we refer to ion methods only (i.e. no LC/GC)
 MALDI-ion mobility-orthogonal TOF MS (MALDI-IM-oTOF)
– Used to study biomolecular structure
– Detection limit approaches conventional MALDI-MS
 A MALDI-IM-oTOF experiment can simultaneously give
mass spectra and molecular “conformation” (size and
overall shape) information on desorbed ions.
 Applications: mixture analysis, proteomics, analysis of
complex tissues and micro-organisms.
A. S. Woods, et al. Anal. Chem., 2004, 76, 2187-2195.
Hyphenated Ion Methods
 MALDI-IM-oTOF
enabling technology:
medium-pressure IM
cells that do not lose
ions in the differential
pumping region
 Mobility differences for

different biomolecule
classes can differ by ~15%
2D resolution!
A. S. Woods, et al. Today’s Chemist at Work, May 2004, 32-36.
References
 Atomic and Molecular Mass Spectrometry
– Optional:
– F. W. McLafferty, “Interpretation of Mass Spectra”, 3rd Ed.,
University Science Books, Mill Valley, CA (1980).
– H. A. Strobel and W. R. Heineman, “Chemical
Instrumentation, A Systematic Approach”, Wiley, 1989.
– Skoog et al. Ch 11 and 20.
 Ion Mobility Spectrometry
– Optional:
 G. W. Eiceman, Critical Rev. Anal. Chem., 1991, 22, 471-489.
 D. C. Collins and M. L. Lee, “Developments in ion mobility
spectrometry – mass spectrometry”, Anal. Bioanal. Chem., 2002,
372, 66-73.