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Vibrational Spectroscopy for
Pharmaceutical Analysis
Part VI. Interpretation of Infrared Spectra & Applications
Rodolfo J. Romañach, Ph.D.
ENGINEERING RESEARCH CENTER FOR
STRUCTURED ORGANIC PARTICULATE SYSTEMS
RUTGERS UNIVERSITY
PURDUE UNIVERSITY
NEW JERSEY INSTITUTE OF TECHNOLOGY
UNIVERSITY OF PUERTO RICO AT MAYAGÜEZ
10/11/2005
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Interpretation of Mid-IR Spectra
• Mid-IR spectroscopy is a powerful tool for
chemists that want to determine the structure of
a process impurity or degradation product.
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Dividing Line
 1500 cm-1 dividing line: above 1500 cm-1 if a band has a
reasonable intensity, it is a group frequency.
 Below 1500 cm-1 the band may be either a group or
fingerprint frequency.
 Below 1500 cm-1 called the fingerprint region.
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Group Frequencies
 Characteristic of functional groups such as -O-H,
-CH3, -COCH3, and COOH.
 Determined empirically by studying the spectra of
many related molecules.
 Always found in the spectrum of a molecule
containing that group, and always occurs in the
same narrow frequency range.
 The form of the bands is nearly always the same
in every molecule containing that group.
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Fingerprint Frequencies
 Highly Characteristic of the Specific Molecule.
 Due to Vibrations of the Molecule as a whole.
 The numerical values cannot be predicted in most
cases.
 Valuable in characterizing a molecule.
 Fingerprint region is useful for discriminating
between molecules that resemble each other.
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Group Frequencies
 O-H Stretch – Position is Highly Dependent on
Hydrogen Bonding.
 Intense – Easy to Identify.
 Carboxylic Acids – Very broad and strong, form
dimers.
 This band will grow in intensity if you have a
hygroscopic material.
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Benzoic Acid Spectrum
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Propylene Glycol – Ref. Std.
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C-O Single Bonds
 This stretching will be observed for ethers, alcohols, esters,
anhydrides, and carboxylic acids.
 Present in carbohydrates (lactose, microcrystalline cellulose,
mannitol are commonly used in pharmaceutical processing.
 Very intense bands in 1000 – 1250 cm-1 region which are
subject to erratic shifts from small structural changes.
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Carbohydrate Spectrum.
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Cellulose Acetate
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C=O Stretch
 Provides a very strong signal and is found in many
organic molecules.
 It occurs in a region of the spectrum where few other
functional groups are observed.
 Range of carbonyl frequencies is from 1750 ± 200 cm-1.
The changes in frequency have been thoroughly studied
and provide significant structural information.
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Acetophenone
–
Notice Weak C-H stretch area in comparison with C=O
stretch
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Corn Oil
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KBr pellet spectrum of aromatic compound.
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KBr pellet spectra.
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Spectra of Two Different Crystal Habits
N.R. Sperandeo, A. Karlsson, S. Cuffini, S. Pagola, and P.W. Stephens, AAPS
PharmSciTech 2005; 6 (4) Article 82 (http://www.aapspharmscitech.org).
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Information from PNQ Spectra
• Spectra are very similar, indicating same
compound.
• O-H and N-H were free (not involved in hydrogen
bonding) then absorbances near 3500 cm-1 would
be observed.
• The fact that N-H and O-H are near 3200 cm-1 is
indicative that they are involved in hydrogen
bonding.
• Spectra were obtained with KBr pellets
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