s
i
ANANBIOANAL - 2010
Pharmaceutical R & D Summit
doi:10.4172/2155-9872.1000004
Identification and Characterization of New Drugs Using Mass
Spectrometry
K Srinivasa Rao
Roland Institute of Pharmaceutical Sciences, Berhampur, Orissa, India
M
ass spectrometer can be used in 3 principal ways: firstly, to measure the
molecular weights with very high accuracy; from these can be deduced exact
molecular formulae. Secondly, to detect within a molecule the places at which it
prefers to fragment; from this can be deduced the presence of functional groups
within the molecule. And thirdly, as a method for identifying drug molecules by
comparison of their mass spectra with libraries of digitized mass spectra of known
compounds. Molecular ion gives highly useful information about the identity of the
drug molecule. Fragmentation pattern gives further information about the structure
of the drug molecule. All fragment ions are, however, not of equal significance
to assign the structure to a compound. Intensity of the molecular ion peak in a
mass spectrum depends on the type of the compound. Mass spectra cannot be
interpreted if they contain any misinformation. Unfortunately, even referred journals
and carefully edited collections of the standard spectra sometimes contains spectra
that fail to meet this criterion. Some compounds e.g., alcohols may fail to give a
visible molecular ion peak. Judging whether or not a mass spectrum is credible is
sometimes the most critical step in its interpretation. Most EI mass spectrometers in
use today lack sufficient resolving power to provide accurate mass measurement for
the determination of elemental composition. However, the elemental composition of
an ion can sometimes be determined from the ratios of the peak intensities of the
isotope peaks for that ion to the intensity of the nominal mass peak. Some typical
features may be helpful i.e., if the M+2 peak of the parent ion looks larger than the
M+1 peak, the compound might contain S,Cl or Br. When there is a larger gap and
a peak at 127, iodine may be present. The intensity of the M+1 peak can be used
to know the number of carbons well as nitrogen atoms. In the absence of nitrogen,
the maximum number of carbaon atoms can be calculated by dividing the relative
intensity of the M+1 peak by 1.1. Thus, e.g., a molecule with 12 carbon atoms will
display a M+1 peak of 13.2 per cent. In case nitrogen is present its contribution to
the M+1 peak will amount of 0.4 X number of nitrogen atoms. This quantity must
be subtracted from the measured relative intensity of the M+1 peak to know the
number of carbon atoms. When in a compound Cl, Br, S or Si is present loss of a
proton from the M+2 is likely to enhance the intensity of the M+1 peak. The number
of nitrogen atoms present can be deduced with the help of nitrogen rule. In this talk
we will address, how to identify different drug molecules using mass spectrophomter
with relevant examples.
ANALBIOANAL-2010
O
M
I
C
S
P
i
u
h
b
l
n
g
G
r
o
u
p