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Enantioselective analysis of chiral pharmaceuticals in environment
Edmond Sanganyado and Jay Gan
Department of Environmental Science
University of California Riverside
2
Chiral center
Thalidomide Tragedy
Chiral Pharmaceuticals in the Environment
U.S. Geological Survey, http://toxics.usgs.gov/regional/emc/transport_fate.html 3
Purpose of Study•Develop method for enantioseparation of chiral pharmaceuticals
•Determine the enantiomeric composition of chiral pharmaceuticals in the environment
4
Enantioseparation achieved in normal phase HPLC
Rs 1.10
Rs 1.66
Rs 7.95
5
Enantioseparation on Vancomycin based column
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A: 80 % 20 mM ammonium acetateB: 20 % organic modifier
Enantioseparation on Vancomycin based column
• Effect of amount and type of inorganic salts
• van’t Hoff plots
• Mechanism of chiral recognition7
Mobile Phase: •Methanol + 0.1% acetic acid + 0.1% triethylamine•1.0ml/min flow rate
Effect of type and amount of ammonium salt on Rs and α
8
Effect of pH on enantioseparation
9
Effect of temperature on Rs and α in PIM
10
Temperature dependence of retention and selectivity factors
11
Mobile phase Atenolol Fluoxetine
Additive Conc.,
mM
-ΔH˚i
kJ/mol
ΔSi*
J/mol
r2i -ΔΔH˚
kJ/mol
-ΔΔS r2 -ΔH˚i
kJ/
mol
ΔSi*
J/mol
r2i -ΔΔH˚ -ΔΔS r2
Ammonium
acetate
20 3.50
4.11
-5.61
-6.86
0.989
0.993
0.61 1.25
0.999 4.05
4.99
-9.33
-11.82
0.996
0.996
0.94 2.49 0.998
15 3.11
3.70
-3.07
-4.20
0.998
0.999
0.59 1.14 0.999 3.78
4.68
-6.64
-9.00
0.999
0.999
0.90 2.36 0.999
10 2.37
2.99
1.26
0.0005
0.997
0.998
0.62 1.20 1 3.09
4.02
-2.00
-4.44
0.999
0.999
0.93 2.45 0.998
4 1.13
1.67
9.47
8.54
0.992
0.996
0.54 0.93 0.997 1.82
2.79
6.96
4.41
0.999
0.999
0.97 2.55 0.999
Ammonium
nitrate
10 0.63
0.47
-2.00
-1.25
0.682
0.997
1.11 2.72 0.877 1.21
2.45
-6.56
-9.73
0.809
0.942
1.24 3.16 0.999
Factors affecting separation of enantiomers: Summary
12
Multiresidue separation and extraction in water
• 1mg/ml racemic standard spiked in 500 ml water• Extraction by SPE using HLB cartridge 13
Work in Progress
14
Conclusion• Analysis of drugs at trace levels in environmental
matrices poses a significant analytical challenge.
• Development of methods for the enantioseparation
of chiral drugs is vital in the understanding of
their occurrence, fate and toxicity in the
environment.
• Chiral separation is important for preparing
enantiopure compounds required in
biodegradation and toxicity experiments.
15
Acknowledgements
16