Mass Spectrometry

Which Ionization technique is more common for pharmacists?

Either:

Electrospray Ionization

1. Liquid sample droplets are forced through a charged capillary; forms small charged droplets

2. Desolvation, droplets are evaporated, increases surface charge density as charged particles are brought closer

3. Close together positive charges repel and form small gas phase ions

or

For destructive techniques, electron impact is most common

Important Peaks

Parent/Molecular Ion Peak: M⁺, the peak of the full molecule that’s been ionized, no splitting

Base Peak: tallest peak, highest relative abundance; the most stable ion fragment

• is set to 100%, other peaks are shown relative to it

M+1 Peak: due to C¹³ isotope; check relative abundance

• will be around (10)x% of M⁺ peak (increases by around 10 for every carbon atom)

M+2 Peak: due to Br or Cl

• Br: 1:1 abundance

• Cl: 3:1 abundance

Halogen Weights

Bromine: 79/81

Chlorine: 35/37

Rule of 13

A shorthand rule for estimating the number of carbons in a molecule

• note: only an ESTIMATE; do not rely on exclusively

1. Divide Molecular Mass by 13 (mass of CH)

2. Quotient = Carbons, Quotient + Remainder = Hydrogens

3. Substitute a single carbon for an O, N, etc if need be

4. Determine IHD (Index of Hydrogen Deficiency)

Index of Hydrogen Deficiency

Formula:

(2C+2 - H - X + N)/2

Ring: 1 IHD

Double Bond: 1 IHD (a triple counts as two doubles)

Phenyl Ring: 4 IHD (3 doubles + ring)

High-Resolution Mass Spectrometry

more specific and precise, can help differentiate between similar spectra

Precision of 0.0001 amu

Fragmentation Patterns (General)

First Priority:

weak bonds break in preference to strong bonds

Second Priority:

stable fragments form in preference to unstable fragments

Can either break heterolytically or homolytically

Heterolytic Cleavage:

if C-Z, and Z is more electronegative, electrons will move towards Z

Homolytic Cleavage:

if C-Z or C-C and have equal electronegativity, electrons will split between the two

Note: ions are detected, not neutral radicals

Note: fragments can dehydrogenate, saturate, or alkyl/hydride shift

Types of Fragmentation

Heterolytic Cleavage:

• electron moves to more electronegative atom

Homolytic Cleavage:

• also called Alpha Cleavage

• separates at alpha carbon

• electron from heteroatom and carbon NEXT to alpha-carbon

• forms double bond

Dehydration:

• takes hydrogen from gamma-carbon

McLafferty Rearrangement:

• takes hydrogen from gamma-carbon

• double bond between beta and gamma

• cuts between alpha and beta