1. M ONITORING P RECURSOR C HEMICALS OF M ETHAMPHETAMINE THROUGH E NANTIOMER P ROFILING Laura Fairburn and Mike Rusak

2. O VERVIEW What are Methamphetamines? Methods of Synthesis Precursor Compounds Different Stereoisomers Enantiomer Profiling How it is done How they source the drugs using it Methamphetamines in the Legal System

3. WHAT ARE METHAMPHETAMINES? A class of compounds with a phenylethylamine core and a methyl group on the alpha carbon Contains a methyl substituted off the amine Very similar structure to epinephrine

4. STEREOISOMERS OF METHAMPHETAMINE R-enantiomer Decongestant in nasal inhalers Precursor for manufacturing l-deprenyl S-enantiomer 5 times more active than R Predominantly used as a stimulant Although the S-enantiomer is far more popular, the appearance of the R-enantiomer continuing to grow within mixtures

5. SOURCES OF EACH ENANTIOMER S(+)-methamphetamine 1R,2S(-)-ephedrine, 1S-2S(+)- pseudophedrine have same C-2 configuration, so can be used as precursors for R(-)-methamphetamine 1R,2R(-)-methylpseudoephedrine, 1S,2R(+)-methylephedrine Mixtures of both exhibit high purity with little trace amounts of ephedrine compounds

7. PRECURSOR COMPOUNDS

8. Reductive Amination “Nagai” Route using Red Phosphorus

9. WHAT IS ENANTIOMER PROFILING? Most routinely used in Methamphetamine due to chiral nature Determination of the ratio of the chiral isomers in order to understand the precursors used With use of statistics, it can help understand smuggling patterns internationally

10. TECHNIQUE USED FOR ENANTIOMER PROFILING For this study, 433 different samples were tested and compared to two standards of R and S methamphetamine-d5. GS-MS was used Sample Preparation A variety of standard solutions of both enantiomers were used Calculation of LOD and R(-)-enantiomer ratio

12. E NANTIOMER R ATIOS OF M ETHAMPHETAMINE

13. U SE OF E NANTIOMER P ROFILING TO S OURCE M ANUFACTURERS As R-(-) sources weren’t as strictly regulate, the appearance of them in methamphetamines dramatically increased as year past This also could mean changes in smuggling routes and external sources

14. M ETHAMPHETAMINES IN THE L EGAL S YSTEM Arrests have increasing substantially over the 10 years More strict regulations temporarily resulted in a drop in manufacturers Large-scale producers weren’t affected, while small-scale producers were hit hard

15. L EGAL R EGULATIONS OF M ETHAMPHETAMINES It is an Illegal Substance in Canada and the United States Regulations can be altered to relate to current methods of synthesis and smuggling routes Both which can be determined through the technique of enantiomer profiling

16. C ONCLUSION Enantiomer Profiling is well suited for rapid and simultaneous determination of enantiomers of amphetamine, phenol alkylamines and hydroxyamines It is the standard for testing a very predominant, increasingly popular drug