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CID and HCD

Definition

Collision-induced dissociation. The precursor is accelerated and collides with a neutral gas (nitrogen, argon, helium) in the collision cell. Internal energy converts to bond-cleavage. Higher-energy collisional dissociation (HCD) on Orbitrap instruments uses a dedicated cell at higher energy and gives more reproducible fragmentation than ion-trap CID.

CID mechanism
Precursor ion collides with neutral gas, converting kinetic to internal energy
Common collision gases
Nitrogen, argon, helium
HCD platform
Dedicated higher-energy cell on Orbitrap instruments
HCD advantage
More reproducible fragmentation than ion-trap CID

Common questions

Why does HCD give more reproducible spectra than trap-based CID?+

HCD uses a dedicated collision cell with a fixed, higher collision energy applied outside the ion trap, avoiding the low-mass cutoff and energy-dependent trapping effects that make ion-trap CID spectra vary more between instruments and runs.

What is the low-mass cutoff problem in ion-trap CID?+

Ion traps cannot stably retain fragment ions much below about a third of the precursor's mass during fragmentation, so small diagnostic fragments can be lost, which HCD's beam-type collision cell does not suffer from.

Which is preferred for forensic drug or toxin identification?+

HCD is generally favoured on Orbitrap systems for library-searchable, reproducible fragment spectra, while CID remains widely used on other platforms and for certain fragmentation behaviours HCD does not reproduce as cleanly, such as some neutral losses.

Related terms

Accurate Mass and Mass Defect
On a Q-TOF or Orbitrap, the measured m/z is reported to four decimal places at parts-per-million accuracy. The deviation from the nominal...
Deuterated Internal Standard
An isotopologue of the analyte where two to five hydrogens are replaced by deuterium. Same chromatographic and ionisation behaviour, slightly higher mass....
MRM (Multiple Reaction Monitoring)
A targeted MS/MS scan mode on a triple quadrupole that monitors specific precursor-to-product ion transitions, with two transitions per analyte (quantifier and...
Quantifier and Qualifier Transitions
The most intense MRM transition is the quantifier and is used for the concentration calculation. The second (and sometimes third) transition is...
Tandem MS (MS/MS)
Two stages of mass selection in series with a fragmentation step in between. The first stage selects a precursor ion, a collision...

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