The use of Enantiomeric Profiling to Determine Smuggling Patterns of Methamphetamine

1. The use of Enantiomeric Profiling to Determine Smuggling Patterns of Methamphetamine William Kou Jonathan Mertz

2. Overview • 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

3. Ephedrine • 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

5. About MethylamphetamineEnatiomers • 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, anti-depressants, and as a decongestant

6. How It Was Done • 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.

7. 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

8. Like a puzzle piece that may, or may not fit together.

9. Shortfalls to this Technique • 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!

10. How to Fool this Technique • 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.

11. Epimerize a portion of the final product • Then recombine 33% by mass Epimerize 100% 33% R

12. Which leaves you thinking, there must be a better way to do this… Well... There is.

13. Suggested Alternative 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

14. “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’”

15. 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.

18. Summary

19. References • Rapid Commun. Mass Spectrom. 2009 http://onlinelibrary.wiley.com/doi/10.1002/rcm.4109/pdf • Forensic Science International 173 (2007) - Monitoring precursor chemicals of methamphetamine through enantiomer profiling