522
MORRISON ET AL.
7. Baselt RC. Disposition of toxic drugs and chemicals in man. Foster City,
CA: Chemical Toxicology Institute; 2000. p530–531.
obutyric acid remain after derivatization and evaporation.
Further steps are therefore required before chromatography,
for example, addition of larger volumes/repeated additions
of ethyl acetate (approximately 200–300 ll) prior to evapora-
tion under N2. This reagent was not investigated further as
an important aim of the research was simplification of the
derivatization procedure.
8. Cruickshank CC, Dyer KR. A review of the clinical pharmacology of
methamphetamine. Addiction 2009;104:1085–1099.
9. Armstrong DW, Rundlett KL, Nair UB, Reid GL III. Enantioresolution of
amphetamine, methamphetamine, and deprenyl (selegiline) by LC, GC,
and CE. Curr Sep 1996;15:57–61.
10. Pihlainen K, Kostiainen R. Effect of the eluent on enantiomer separation
of controlled drugs by liquid chromatography-ultraviolet absorbance
detection-electrospray ionisation tandem mass spectrometry using vanco-
mycin and native b-cyclodextrin chiral stationary phases. J Chromatogr A
2004;1033:91–99.
Internal Standards
Internal standards were not used in this study as the focus
here was on the ratios of enantiomers. However, should
quantification of methylamphetamine be required, for exam-
ple, when using mass spectrometric detectors,24,25 deuter-
ated analogs of methylamphetamine are available from com-
mercial sources as mixtures of optical isomers.
11. Iwata YK, Inoue H, Kuwayama K, Kanamori T, Tsujikawa K, Miyaguchi
H, Kishi T. Forensic application of chiral separation of amphetamine-type
stimulants to impurity analysis of seized methamphetamine by capillary
electrophoresis. Forensic Sci Int 2006;161:92–96.
12. Rasmussen LB, Olsen KH, Johansen SS. Chiral separation and quantifica-
tion of R/S-amphetamine, R/S-methamphetamine, R/S-MDA, R/S-
MDMA, and R/S-MDEA in whole blood by GC-EI-MS. J Chromatogr B
2006;842:136–141.
CONCLUSION
The gas chromatographic analysis of the optical isomers of
important compounds found within the Emde synthesis of
methylamphetamine, including the starting materials and
intermediates, can be achieved using readily available deriva-
tizing reagents in combination with a chiral stationary phase.
The derivatization procedure is quick and simple. In parti-
cular, the enantiomers of pseudoephedrine, methylamphet-
amine, and chlorinated intermediates can be separated in a
run time of approximately 40 min, using PFPA as a derivatiz-
ing reagent. A separate derivatization procedure with trifluoro-
acetic anhydride is required for the separation of ephedrine
enantiomers. HFBA requires a more labor-intensive derivati-
zation procedure and is therefore not recommended for this
type of analysis.
13. Collins M, Cawley AT, Heagney AC, Kissane L, Robertson J, Salouros H.
d
13C, d15N, d2H isotope ratio mass spectrometry of ephedrine and pseu-
doephedrine: application to methylamphetamine profiling. Rapid Com-
mun Mass Spectrom 2009;23:2003–2010.
14. Dujourdy L, Dufey V, Besacier F, Miano N, Marquis R, Lock E, Aalberg L,
Dieckmann S, Zrcek F, Bozenko JS Jr. Drug intelligence based on organic
impurities in illicit MA samples. Forensic Sci Int 2008;177:153–161.
15. Inoue H, Iwata YT, Kuwayama . Characterization and profiling of meth-
amphetamine seizures. J Health Sci 2008;54:615–622.
16. Puthaviriyakorn V, Siriviriyasomboon N, Phorachata J, Pan-Ox W, Sasaki
T, Tanaka K. Identification of impurities and statistical classification of
methamphetamine tablets 9Ya-Ba seized in Thailand. Forensic Sci Int
2002;126:105–113.
17. Lee JS, Yang WK, Han EY, Lee SY, Park YH, Lim MA, Chung HS, Park
JH. Monitoring precursor chemicals of methamphetamine through enan-
tiomer profiling. Forensic Sci Int 2007;173:68–72.
The identification of chlorinated intermediates within
methylamphetamine samples is indicative of the Emde syn-
thetic route rather than the Birch or Nagai routes.
18. United Nations Office of Drugs and Crime. Recommended methods for
the identification and analysis of amphetamine, methamphetamine and
their ring-substituted analogues in seized materials. Vienna, Austria:
United Nations Office of Drugs and Crime; 2006.
19. Flores-Parra A, Sua´rez-Moreno P, Sa´nchez-Ru´ız SA, Tlahuextl M, Jaen-
Gaspar J, Tlahuext H, Salas-Coronado R, Cruz A, No¨th H, Contreras R.
Chlorination reactions of ephedrine revisited. Stereochemistry and func-
tional groups effect on the reaction mechanisms. Tetrahedron: Asymme-
try 1998;9:1661–1671.
ACKNOWLEDGMENTS
The authors thank Mr. C. McGinness, University of the West
of Scotland, for technical assistance, and Dr. David Adam,
School of Chemistry, University of Glasgow, for NMR analysis.
20. Allen AC, Kiser WO. Methamphetamine from ephedrine. I. Chloroephe-
drines and aziridines. J Forensic Sci 1987;32:953–962.
LITERATURE CITED
21. Kim HK, Choi YH, Erkelens C, Lefeber AWM, Verpoorte R. Metabolic
fingerprinting of Ephedra species using 1H-NMR spectroscopy and prin-
cipal component analysis. Chem Pharm Bull 2005;53:105–109.
1. United Nations Office of Drugs and Crime. World Drug Report 2009.
Vienna, Austria: United Nations Office of Drugs and Crime; 2009.
2. US Drug Enforcement Administration. Methamphetamine. Available at:
16, 2010.
22. Uncle Fester. Secrets of methamphetamine manufacture, 7th ed. Green
Bay, Wisconsin: Festering Publications; 2005. p129–132.
23. Astec CHIRALDEXTM GC columns:
A guide to using cyclodextrin
3. Matteucci MJ, Auten JD, Crowley B, Combs D, Clark RF. Methamphet-
amine exposures in young children. Pediatr Emerg Care 2007;23:
638–640.
bonded phases for chiral separations by capillary gas chromatography,
Sigma-Aldrich Co., 2007.
24. Bjørk MK, Nielsen MKK, Markussen LØ, Klinke HB, Linnet K. Determi-
nation of 19 drugs of abuse and metabolites in whole blood by high-
performance liquid chromatography—tandem mass spectrometry. Anal
Bioanal Chem 2010;396:2393–2401.
4. Grant P. Evaluation of children removed from a clandestine methamphet-
amine laboratory. J Emerg Nurs 2007;33:31–41.
5. Sexton RL, Carlson RG, Leukefeld CG, Booth BM. Patterns of illicit meth-
amphetamine production (‘‘cooking’’) and associated risks in the rural
south: an ethnographic exploration. J Drug Issues 2006;36:853–876.
25. Wu Y-H, Lin K-L, Chen S-C, Chang Y-Z. Simultaneous quantitative deter-
mination of amphetamines, ketamine, opiates and metabolites in human
hair by gas chromatography/mass spectrometry. Rapid Commun Mass
Spectrom 2008;22:887–897.
6. ‘‘ICE’’ L-methamphetamine HCl on the West Coast. Microgram Bull
2003;36:251.
Chirality DOI 10.1002/chir