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Mass Spectrometry
CHEN Ping
2013.12.06
1
Outline
I. Introduction
V. Summary
Introduction
More than half of the currently approved drugs are
chiral molecules.
Develop single enantiomer drugs
Reducing the required dose
Increasing the potency
Improving the safety profile
Asymmetric synthesis
(Catalysts screening)
7 of the 10 best-selling US
pharmaceutical products are single
enantiomer.
Mass Spectrometry
Chiral Recognition
Chiral analysis
(Quality control)
Ranking of the top 10 best-selling US pharmaceutical products in 2011 was obtained
from webpage: http://www.imshealth.com/.
Introduction
Hyphenated MS techniques
Coupling of chiral sensitive analytical tools with MS
Liquid Chromatography-Mass Spectrometry (LC-MS)
Gas Chromatography-Mass Spectrometry (GC-MS)
Capillary Electrophoresis-Mass Spectrometry (CE-MS)
Capillary Electrochromatography-Mass Spectrometry
(CEC-MS)
Supercritical Fluid Chromatography-Mass Spectrometry
New detector:
Mass Spectrometer (MS)
(SFC-MS)
Advantages:
Limitations:
Hyphenated MS techniques
Direct approach:
Analysis of covalent
Analysis of noncovalent
diastereomeric
diastereomeric
complexes
complexes
Separated by
conventional methods
Derivatized
by the CS to
form
covalent
complexes
Form
transient
bond with
CS
Hyphenated MS techniques
2.
MS is used solely in chiral analysis based on
different methods of chiral recognition
Host-Guest (H-G) Associations
Guest Exchange Ion-Molecule Reactions
Chiral Recognition Based on Complex Dissociation
CS (host)
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Iref*(1) IR
Iref*(2) IS
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Enamine
Widely accepted
Not been validated
experimentally
16
Problem:
Enamine mechanism not been
validated experimentally
Guests
18
En
ent-2
En
Im
Back reaction
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Summary
I. Chirality is significant
II. Concepts of hyphenated MS techniques
III. Mass Spectrometric Chiral Recognition Mechanisms
IV. An example that using chiral recognition to solve mechanistic
problem
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Mass Spectrometry
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Metal: Cu2+
Ref: two L-Trp
Analytes: (+)-ephedrine
()-ephedrine
I+/I ref*(1) =
-A
3.8
I-/I ref*(2) =
0.91
R (+)-ephedrine
chiral = 4.7
The interaction between
and ref* is stro
-Ref
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Introduction
Asymmetric
Synthesis
Catalyst screening
Chiral
Drug
Chiral
Analysis
Chiral
Recognition
Quality control
Chiral
Resolution
Chromatography
Mass Spectrometry
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31
T. R. Brandon, J. Am. Soc. Mass. Spectrom. 2004, 15,
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