Mass Spectrometry applications in Medicinal Chemistry
Mass spectrometry is a very powerful and versatile method. Here I try to give some outlines about HOW TO extract a INFORMATION FROM MASS SPECTRA---
Here the presentation explains
For a Mass of 40 kDa, there is a 4 Da POSSIBLE error
And this mass spec also use to ……
This is wht the diagrammatic flow chart of mass spec instrument
Sample is introduced in to the mass spec----- Depending upon the type of the sample….
As Mass spectrometry is a very powerful method to analyse the structure of organic compounds,
Usually what v will c aftr getting a spectrum? Nothing we sit on comp n draw a str of reqd product n match the mass with tht, if it is thr KHUSH!! And also we put more effort to isolate pure product so definitely get good spectra. But I want summarizes some other possibilities to check the information content. What r the other peaks which are come along? N wht they signifies. U consider the spectra as a content of pure compound… as no peaks at all in higher range after Mion peak
in med. Chem. It is applicable in the measurement of …..
a significant breakthrough in mass spectrometry.
Ritalin- contains Methyl pheniphenidate
Thank you very much
Mass Spectrometry Applications and spectral interpretation: Basics
applications in Medicinal
Mass spectrometry is a very
powerful and versatile analytical
Extensively used in every fields to
detect one or the other things.
Here I try to give some outlines
about HOW TO extract a
INFORMATION FROM MASS
What is mass spectrometry?
Where are mass spectrometers used?
How does a mass spectrometer work?
What information can it provide?
Interpretation of spectra. and
Applications in medicinal chemistry.
What is Mass Spectrometry?
Analytical tool measuring molecular weight
(MW) of sample.
Only picomolar concentrations required.
With an high accuracy and within 5 ppm of
std. Error for small organic molecules.
For a mass of 40 kDa, there is a 4 Da error.
This means it can detect amino acid
substitutions / post-translational modifications
in biological systems.
Where are they used?
Analysis of proteins, peptides, oligonucleotides
Drugs discovery, combinatorial chemistry, pharmokinetics,
Neonatal screening, haemoglobin analysis, drug testing
Water, food, air quality
Mass Spectrometry is also used to...
Detect and identify the use of steroids in athletes(Doping)
Ex. Sunita Rani’s case!!!
Monitor the breath of patients by anesthesiologists during
Determine the composition of molecular species found in space
Adulteration in food stuff
Ex. Presence of pesticide in …..
How does a Mass
3 fundamental parts: the ionisation source, the
analyser, the detector
Samples easier to manipulate if ionised
Separation in analyser according to mass-tocharge ratios (m/z)
Detection of separated ions with their relative
Signals sent to data system and formatted in a
Either directly or via chromatography for
component separation (HPLC, GC,
Ionisation can be positively charged (for
proteins; Org. molecules) or negatively
charged (for saccharides and
Electron Impact (EI)
Chemical Ionisation (CI)
Atmospheric Pressure Chemical Ionisation
Fast Atom Bombardment (FAB)
Field Desorption / Field Ionisation (FD/FI)
Electrospray Ionisation (ESI)
Matrix Assisted Laser Desorption
• Magnetic Sector
• Time of flight (tof)
• Quadrupole ion trap
• Fourier Transform Ion Cyclotron Resonance
The resolving power of analysers
The respective resolving powers correspond to the resolution typically
obtained for time-of-flight, quadrupole, and Fourier-transform mass
analyzers. Notice that the individual isotope peaks can be distinguished
at the higher resolution.
• Photo Multiplier
• Faraday Cup
Detector monitors ion current, amplifies it and then transmits signal to
Mass spectrometry is a very powerful
method to analyse the structure of organic
compounds, but suffers from 3 major
1 It is a destructive method
2 Compounds cannot be characterised without clean
3 The dynamic properties of molecules can not be
What Molecular ion peak tells !!
Most of the times chem. Strs. of the products are
known are presumed.
Sometime unexpected peaks will come then we’ll
scratch our head.
And we try to see +23/ +39 peaks(Na/ K adducts)
If MI is observed what else we can see for further
mass no- odd/even
Natural abundance of
Remember and Review!
The Rule of Thirteen – Molecular Formulas from Molecular
When a molecular mass, M+, is known, a base
formula can be generated from the following equation:
the base formula being:
For this formula, the HDI can be calculated from the
HDI = ( n – r + 2 )
How to interpret our spectra?
Check the quality of the data; does the total ion spectrum look
Does the mass spectrum show significant peaks above the
Identify any major peaks.
Look for telltale isotope patterns.
Remember the Nitrogen Rule. (The Nitrogen Rule: A neutral
compound containing an odd number of nitrogen atoms will
always have an odd molecular mass.)
Do the masses fit with the proposed structure?
Have you used the appropriate masses in your calculations?
How do I interpret my spectra?
Identify the MI
Check isotope pattern - halogens, sulphur etc.
Odd/Even Mass - Nitrogen Rule
If FAB check intensity of MI - aromatic or aliphatic
Accurate mass - calculate r + db
See neutral losses out of your mass.
Amine protecting groups
r + db = x - 0.5y + 0.5z + 1
In Med. Chemistry
Accurate molecular weight measurements:
Unknown sample, Purity of sample, About other side products.
enzyme activity, chemical modification, protein digestion.
Natural products, unknown products through fragmentations.
Identification of Mechanism of actions:
Both covalent n noncovalent interactions.
Active site Identifications:
Quantifying the amount of a compound in a sample using
carefully designed methods.
Impurity profiling for the bulk drugs.
Its an atmospheric pressure source capable of ionizing liquid, solid, and
gas samples in real time.
Principle: on an atmospheric pressure interaction of a sample with longlived electronic excited-state atoms or molecules and atmospheric gases.
The system uses helium or nitrogen to produce metastable atoms or
molecules that interact with the analytes.
-lends to the analysis of samples
without any preparation and provides
data with accurate mass measurement.
A complete analysis can be done
within minutes by simply holding a
sample in the open gas stream.
The DART can even analyze samples directly on
surfaces such as concrete, currency, food, pills
The revolutionary DART ion source gives an
entirely new meaning to the phrase "open access".
MS is a highly applicable analytical tool in
The full structural information can get out of
single mass spectrum with min. qty. of sample.
Elemental analysis can b carried by using
In his book,
“Rays of Positive Electricity” (1913),
“I feel sure that there are many problems in
chemistry which could be solved with far greater ease by
this than by any other method. The method is surprisingly
sensitive,……..requires an infinitesimal amount of material
and does not require this to be specially purified.”
Thank you very much