Hyphenated MS

Sri Noegrohati
Fac of Pharmacy
Gadjah Mada University

Sri Noegrohati, UGM 1

MS
„ Based on ionization of gas phase molecule followed by
analysis of the masses of the ions produced
„ Provides:
… Molecular/Atomic weights of analyte
… Structural details of analyte
… Sensitive, accurate and precise quantitation
„ Need pure compounds for qualitative/structural
determinations

Sri Noegrohati, UGM 2

Atomic vs. Molecular MS
Atomic: Molecular:
„ Detecting ions of elements „ Detecting ions of molecules
using the MS. in the MS.
„ Usually works over the „ Usually works over the
mass range of about 2-300 mass range of about 2-900
amu. amu +
… Usually singly charged … higher mass ranges with
species multiply charged ions
„ Most common introduction … measuring m/z
source is the ICP (plasma) „ Common introduction
„ Used for qual. and quant. sources are direct insertion,
elemental analysis of GC, HPLC.
samples, identification of „ Also used for qual. &
isotopes, isotope ratio quant. Analysis.
determination, etc.
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 • Sample heated (<400 °C) in small external oven
• Vapor admitted to ionizer through valve
• Gas stream added to entrain analyte

Sri Noegrohati, UGM 4

 • Sample vial inserted through air-lock into ionizer chamber
• Vial heated to vaporize sample
• Vial can be reduced to capillary or surface plate for small
quantities
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 What about Mixtures?

use an
inline
separation
just prior to
obtaining
mass
spectrum:

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MS interface
„ The interface transport the effluent from GC/LC to the
MS
„ The analyte should not
… Condenses in the interface
… Decompose before entering the ion source
… The gas load entering the ion source must be within
the pumping capacity of the MC

Sri Noegrohati, UGM 7

ICP-MS

„ ICP: great source of

atomic ions
„ many elements
„ >90% ionized at ICP
temperatures (8-
10,000 K)

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 ICP-MS: Sampling Ions

ICP: Skimmer Cone

•8000 K
•1 atm pressure

Sampling Cone Expansion Zone

(water-cooled) (1 torr)

Sri Noegrohati, UGM 9

ICP-MS: Results

With Quad Mass Analyzer:

• unit mass resolution
• detection limits: sub-ppb
• > 4 decades LDR
• rapid scanning
• isotope ratio information available

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GC-MS

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GC-MS interface

„ Use capillary column → insert the exit end into MS ion

source → heat the capillary column above the boiling
point to eliminate cold spot (must not condense)
„ Microbore or packed column → use Jet separator

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 GC-MS interface

The Jet Separator

„ interface GC effluent (at atmospheric
„ pressure) into reduced pressure Mass Spec?
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LC-MS

„ Trickier than GC-MS (condensed phase):

… convert to vapor phase
… remove solvent
… ionize

„ Strategies
… Moving Belt Interface
… Particle-Beam/Therma-Spray™
… Direct: Electrospray Ionization

Sri Noegrohati, UGM 14

 Electrospray Ionization (ESI)

ƒ Introduce sample solution through capillary

ƒ Apply high-voltage (1-8 kV) to capillary
ƒ Get desolvation, charged ions – at atmospheric pressure
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 „ droplets formed with applied charge
„ solvent evaporates:
… droplet size decreases, charge density increases
„ “Coulombic Explosion”
… produces ions with multiple charges

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„ ions sent to heated capillary
„ further elimination of solvent
„ reduced-pressure interface with skimmer
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„ High Multiple Charges
„ Ideal for high-MW biomolecules
„ puts m/z within mass range of common mass analyzers
„ Low Fragmentation
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„ Benchtop GC-MS, and bench-sized ICP-MS instruments with
quads are now mainstay analytical instruments in many labs!
„ Vacuum controls (and low vacuums) are key.
… Ions will not behave “independently” if they are near other
ions. High vacuums (low pressures) make each ion
behave like it was not around any other ions.
„ Eventually, the MS will get dirty with old analyte molecules or
ions collected inside the MS.
… You can clean the sources and even the rods in a quad
(extreme case) with solvent.
… The rest of the MS is usually heated and can be baked
out!

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