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Chromatographic separation of R-(−)/S-(+)-enantiomers of amphetamine and methamphetamine: differentiation between single methamphetamine consumption and co-consumption with amphetamine using enantioselective quantitative LC-MS/MS analysis

  • Cornelius HessEmail author
  • Moritz Losacker
  • Alexandra Maas
Original Article

Abstract

The differentiation between single methamphetamine consumption and co-consumption with amphetamine is difficult, however possible by enantioselective analysis due to different preferred synthesis pathways of both substances. We quantified (R)-(−) and (S)-(+)-enantiomers of methamphetamine and amphetamine by a fast liquid chromatographic tandem-mass spectrometric method using a Lux® 3-μm AMP 150 × 3.0 mm analytical column after simple protein precipitation with methanol. Method validation for quantitative detection showed limits of quantification < 5 ng/mL, linearity in a range between 5 and 300 ng/mL and bias and imprecision data < 15%. Overall, 134 plasma samples of police cases from the German regions of Franconia and Northrhine-Westphalia were analyzed for the enantiomers of methamphetamine and amphetamine. In 28 cases, the intake of racemic illicit amphetamine could be demonstrated; (R)-(−) / (S)-(+)-amphetamine concentration ratios in these cases were between 1.38 and 4.50 with most of the ratios being < 2.0. These ratios were compared to a subgroup of 25 consumers with a co-consumption of (S)-(+)-methamphetamine and racemic amphetamine detected by the qualitative proof of (R)-(−)-amphetamine but also by (R)-(−) / (S)-(+)-amphetamine concentration ratios (< 1 in 11 of 25 cases). Within our collective of 106 plasma samples after methamphetamine use, 25 samples showed co-consumption with amphetamine which shows that co-consumption of both stimulants is not a rare scenario. Furthermore, we could show that if non-stereoselective methods are used and the concentration ratio of total methamphetamine/total amphetamine is determined, a reliable estimation of co-consumption is not possible.

Keywords

Enantiomer ratio Quantification Methamphetamine Amphetamine Co-consumption 

Notes

References

  1. 1.
    Daumann J, Gouzoulis-Mayfrank E (2015) Amphetamine, Ecstasy und Designerdrogen. (1. Auflage). Sucht Track 2. Verlag W. Kohlhammer, StuttgartGoogle Scholar
  2. 2.
    United Nations Office on Drugs and Crime (2017) World drug report 2017. [S.l.]: United Nations PubnsGoogle Scholar
  3. 3.
    Cook CE, Jeffcoat AR, Hill JM, Pugh DE, Patetta PK, Sadler BM, White WR, Perez-Reyes M (1993) Pharmacokinetics of methamphetamine self-administered to human subjects by smoking S-(+)-methamphetamine hydrochloride. Drug Metab Dispos 21:717–723PubMedGoogle Scholar
  4. 4.
    Schepers RJF, Oyler JM, Joseph RE, Cone EJ, Moolchan ET, Huestis MA (2003) Methamphetamine and amphetamine pharmacokinetics in oral fluid and plasma after controlled oral methamphetamine administration to human volunteers. Clin Chem 49:121–132PubMedCrossRefGoogle Scholar
  5. 5.
    Vree TB, Gorgels JPMC, Muskens ATJM, van Rossum JM (1971) Deuterium isotope effects in the metabolism of n-alkylsubstituted amphetamines in man. Clin Chim Acta 34:333–344PubMedCrossRefGoogle Scholar
  6. 6.
    Oyler JM, Cone EJ, Joseph RE, Moolchan ET, Huestis MA (2002) Duration of detectable methamphetamine and amphetamine excretion in urine after controlled oral administration of methamphetamine to humans. Clin Chem 48:1703–1714PubMedGoogle Scholar
  7. 7.
    George S, Braithwaite RA (2000) Using amphetamine isomer ratios to determine the compliance of amphetamine abusers prescribed Dexedrine. J Anal Toxicol 24:223–227PubMedCrossRefGoogle Scholar
  8. 8.
    Jirovský D, Lemr K, Ševčík J, Smysl B, Stránský Z (1998) Methamphetamine — properties and analytical methods of enantiomer determination. Forensic Sci Int 96:61–70PubMedCrossRefGoogle Scholar
  9. 9.
    Mendelson J, Uemura N, Harris D, Nath RP, Fernandez E, Jacob P, Everhart ET, Jones RT (2006) Human pharmacology of the methamphetamine stereoisomers. Clin Pharmacol Ther 80:403–420PubMedCrossRefGoogle Scholar
  10. 10.
    Rote Liste (2018) Germany. Instruction leaflet. Attentin®Google Scholar
  11. 11.
    Govi-Verlag: Standardisierte Rezepturen. Govi-Verlag, 2017, ISBN 978-3-7741-1350-3, page 92 (capsulae and liquid), page 93 (drops)Google Scholar
  12. 12.
    Cody JT, Schwarzhoff R (1993) Interpretation of methamphetamine and amphetamine enantiomer data. J Anal Toxicol 17:321–326PubMedCrossRefGoogle Scholar
  13. 13.
    Gunne L-M, Galland L (1967) Stereoselective metabolism of amphetamine. Biochem Pharmacol 16:1374–1377PubMedCrossRefGoogle Scholar
  14. 14.
    Caldwell J, Dring LG, Williams RT (1972a) Metabolism of [ 14 C]methamphetamine in man, the guinea pig and the rat. Biochem J 129:11–22PubMedPubMedCentralCrossRefGoogle Scholar
  15. 15.
    Tetlow VA, Merrill J (1996) Rapid determination of amphetamine stereoisomer ratios in urine by gas chromatography-mass spectroscopy. Ann Clin Biochem 33(Pt 1):50–54PubMedCrossRefGoogle Scholar
  16. 16.
    Weber M, Lessig R, Richter C, Ritter AP, Weiß I (2017) Medico-legal assessment of methamphetamine and amphetamine serum concentrations—what can we learn from survived intoxications? Int J Legal Med 131:1253–1260PubMedCrossRefGoogle Scholar
  17. 17.
    Maas A, Losacker M, Hess C (2018) Chromatographic separation of R/S-enantiomers of amphetamine and methamphetamine: pathways of methamphetamine synthesis and detection in blood samples by qualitative enantioselective LC-MS/MS analysis. For Sci Int 291:138–143.  https://doi.org/10.1016/j.forsciint.2018.08.013 CrossRefGoogle Scholar
  18. 18.
    Peters FT, Drummer OH, Musshoff F (2007) Validation of new methods. Forensic Sci Int 165:216–224PubMedCrossRefGoogle Scholar
  19. 19.
    Wagner JM, McElhinny CJ, Lewin AH, Carroll FI (2003) Stereospecific synthesis of amphetamines. Tetrahedron Asymmetry 14:2119–2125CrossRefGoogle Scholar
  20. 20.
    Verweij A (1989) Impurities in illicit drug preparations: amphetamine and methamphetamine. Forensic Sci Rev 1(1):1–11PubMedGoogle Scholar
  21. 21.
    Allen A, Cantrell TS (1989) Synthetic reductions in clandestine amphetamine and methamphetamine laboratories: a review. Forensic Sci Int 42:183–199CrossRefGoogle Scholar
  22. 22.
    Jones AW, Holmgren A (2012) Concentration ratios of methamphetamine to amphetamine in blood can help to distinguish use of methamphetamine from various mixtures of the two stimulants. J Anal Toxicol 36:634–637PubMedCrossRefGoogle Scholar
  23. 23.
    Slawson MH, Taccogno JL, Foltz RL, Moody DE (2002) Quantitative analysis of selegiline and three metabolites (N-desmethylselegiline, methamphetamine, and amphetamine) in human plasma by high-performance liquid chromatography-atmospheric pressure chemical ionization-tandem mass spectrometry. J Anal Toxicol 26:430–437PubMedCrossRefGoogle Scholar
  24. 24.
    Peters FT, Kraemer T, Maurer HH (2002) Drug testing in blood: validated negative-ion chemical ionization gas chromatographic–mass spectrometric assay for determination of amphetamine and methamphetamine enantiomers and its application to toxicology cases. Clin Chem 48:1472–1485PubMedGoogle Scholar
  25. 25.
    Leis H-J, Rechberger GN, Fauler G, Windischhofer W (2003) Enantioselective trace analysis of amphetamine in human plasma by gas chromatography/negative ion chemical ionization mass spectrometry. Rapid Commun Mass Spectrom 17:569–575PubMedCrossRefGoogle Scholar
  26. 26.
    Giorgi SN, Meeker JE (1995) A 5-year stability study of common illicit drugs in blood. J Anal Toxicol 19:392–398PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Cornelius Hess
    • 1
    • 2
    Email author
  • Moritz Losacker
    • 1
  • Alexandra Maas
    • 1
  1. 1.Institute of Forensic MedicineUniversity of Bonn, Forensic ToxicologyBonnGermany
  2. 2.Institute of Forensic MedicineUniversity of Mainz, Forensic ToxicologyMainzGermany

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