Transcript The downfalls to using Enantiomeric Ratios

William Kou
Jonathan Mertz
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Brief discussion of the techniques used and
how they came to their conclusions
- GC/MS
Shortfalls of the techniques used
How to fool the enantiomer profiling technique
Alternatives of determining the origins of illicit
drugs
- Isotopic Ratio Mass Spectroscopy
Comparative applications of these techniques
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Ephedrine is the reagent of choice to make
methamphetamines
It can be extracted from the Ephedra plant, or Ma
Huang
Ephedrine can also be
synthetically made or
semi-synthetically made.
There are many different
mechanisms to produce
ephedrine
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S-(+)- Methylamphetamine is the illicit drug
and is 6X more active than its R-Enantiomers
The R-(-)- Methylamphetamine is used in the
USA for anti-parkinsonian drugs, antidepressants, and as a decongestant
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The enantiomeric percent ratio of
methylamphetamine samples ceased in Korea
from 1994 – 2005 were analyzed using GC/MS
In order to accomplish this, the samples had to
be converted to diasteriomers using chiral
derivitization reagents
The sample profile is then compared to the
precursors regulated by the government in that
year.
In this article, the sample purity was found to drop after 1996. This
was correlated with the regulations on ephedrine compounds and the
need for manufacturers to find alternative, less pure precursors
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Like a puzzle piece that may, or may not fit
together.
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This technique does not tell you what the
precursors used were, it only gives you the
ratio of the enantiomers in the sample.
The data is then correlated with drug
regulation history.
This is not a very concrete way of coming to
conclusions.
Remember correlation is not always causation!
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Change the enantiomeric composition of your
product.
A change in composition could mean change in
methodology. Where reagents used or a chiral
impurity alters the composition.
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Epimerize a portion of the final product
Then recombine
33% by mass
100%
Epimerize
33% R
Which leaves you thinking, there must be a
better way to do this…
Well... There is.
Isotopic Ratio Mass Spectroscopy (IR/MS)
- Potentially gives location of drug origin
- Shows whether the precursor was synthetic,
semi-synthetic, or natural
- It has been tested and found to be successful
in complimenting the data received from
enantiomeric profiling
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“The major chemical profiling techniques employed in
forensic drug laboratories today focus on organic
impurity profiling, chiral profiling, elemental analysis,
and determination of adulterants and diluents. These
techniques are used to determine the synthetic
pathway and precursors used and to assist law
enforcement agencies in establishing links between
seizures. The measurement of stable isotope ratios of
carbon and other elements, using isotope ratio mass
spectrometry (IRMS), is a more recent profiling
technique and it has been successfully employed to
complement conventional chemical profiling in
determining the geographical origin of cultivated
drugs such as cocaine and heroin, and synthetic route
for drugs such as methylamphetamine and ‘ecstasy’”
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A study by Kiroshima et al, and Makina et al
demonstrated that the different synthetic
origins could be discriminated and that
different batches could also be discriminated.
Different batches of methylamphetamine could
be discriminated even when the purity was so
high that conventional organic impurity
profiles were unhelpful.
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Rapid Commun. Mass Spectrom. 2009
http://onlinelibrary.wiley.com/doi/10.1002/r
cm.4109/pdf
Forensic Science International 173 (2007)
- Monitoring precursor chemicals of
methamphetamine through enantiomer
profiling