Mass Spectrometry 3 Flashcards
MS Interpretation
- General inspection
- Identify base peak (can be (quasi-)molecular ion!)
- Lot of fragmentation or limited number of stable ions? - Identify highest m/z (take isotopes into account!)
- Are you certain this is M+●?
- If so then mass odd/even → nr. of N - Are there “A + 2” elements?
- Use above & find all potential molecular formulae (may help to use 12C/13C calculation)
- Check if formulae can explain OE+.
- Derive structure using all information incl.
- Tables (peaks and losses) - Basic principles
Common Fragmentation Patterns
• Electronegative atom tends to carry + charge
• α-cleavage (bond in α position to site of ionisation):
Fission of bond at atom adjacent to charged atom
– Homolytic
– Heterolytic
• Protontransfer
• Ring structure fragmentation
α Cleavage: EtOH
• Homolytic: 1 electron remains on each atom • O electronegative • 2 electrons: 1 to radical 1 to C=O • Loss of largest radical favoured • + on electroneg atom
• Heterolytic
• Minor here
• Homolytic favoured
if hetero atoms
Homolytic cleavages
- Homolytic α-cleavages:
- OH
- C=O
- C-O-C
- C-NH2
Self-test
• Butan-2-ol. • Indicate the – type(s) of cleavage – fragments lost for the major ions
Common losses for EI
H radical - often a major ion in amines, alcohols and aldehydes
CH3 radical - most readily lost from quaternary C
H2O - readily lost from secondary or tertiary alcohols
Ring structures: Cyclohexanol
Molecular rearrangement prior to fragmentation more likely if ring
Base peak: C3H5O+
- O+•
- Homolytic cleavage 3. H-transfer
Diels-Alder fragmentation
- Can occur with ring systems
• Example: Limonene
Drug molecules
- Abundant molecular ion (codeine)
- Homolytic α-cleavage (bupivacaine)
- Isotope peaks (chloroquinone)
- Tropylium ion (L-dopa)
- McLafferty rearrangement (apronal)
Codeine
- Ring -> fragmentation complex
• 229 closely related to codeine structure
– Does require re- arrangement of ring
• Drugs with extensive ring structures tend to have large molecular ion peaks if…
• No side chains
• Side chains without hetero atoms to direct cleavage
Bupivacaine
• No obvious molecular ion • Homolytic α-cleavage • Directed by N in ring • m/z 140 dominates spectrum – Note that even mass rule does not apply to fragments
Isotope peaks: Chloroquinone
- (A):EI
- α-Homo cleavage
- Adjacent N in chain
- (B):NICI (NI = neg ion CI = chem. ionisation)
Tropylium ion: L-dopa
• Benzyl group • Very stable cation • Other processes may compete • Here: homolytic cleavage
McLafferty rearrangement
• -COOH, Esters • Ketones • Amides • side chain ≥ 3C-atoms • Unusual for drugs – α-cleavage – Long chain lipid (such as fatty acid esters)
More than just MS…
• GC-MS – Ionisation techniques: • EI / PICI / NICI – Applications: • Impurity profiling • LC-MS • Tandem-MS
