Skip to main content

Advertisement

SpringerLink
Log in

Evaluation of drug incorporation into hair segments and nails by enantiomeric analysis following controlled single MDMA intakes

  • Research Paper
  • Published:
Analytical and Bioanalytical Chemistry Aims and scope Submit manuscript

Abstract

Incorporation rates of the enantiomers of 3,4-methylenedioxymethamphetamine (MDMA) and its metabolite 3,4-methylenedioxyamphetamine (MDA) into hair and nails were investigated after controlled administration. Fifteen subjects without MDMA use received two doses of 125 mg of MDMA. Hair, nail scrapings, and nail clippings were collected 9–77 days after the last administration (median 20 days). Hair samples were analyzed in segments of 1- to 2-cm length. After chiral derivatization with N-(2,4-dinitro-5-fluorophenyl)-l-valinamide, MDMA and MDA diastereomers were analyzed by liquid chromatography-tandem mass spectrometry. Highest concentrations in hair segments corresponded to the time of MDMA intake. They ranged from 101 to 3200 pg/mg and 71 to 860 pg/mg for R- and S-MDMA, and from 3.2 to 116 pg/mg and 4.4 to 108 pg/mg for R- and S-MDA, respectively. MDMA and MDA concentrations in nail scrapings and clippings were significantly lower than in hair samples. There was no significant difference between enantiomeric ratios of R/S-MDMA and R/S-MDA in hair and nail samples (medians 2.2–2.4 for MDMA and 0.85–0.95 for MDA). Metabolite ratios of MDA to MDMA were in the same range in hair and nail samples (medians 0.044–0.055). Our study demonstrates that administration of two representative doses of MDMA was detected in the hair segments corresponding to the time of intake based on average hair growth rates. MDMA was detected in all nail samples regardless of time passed after intake. Comparable R/S ratios in hair and nail samples may indicate that incorporation mechanisms into both matrices are comparable.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Pragst F, Balikova MA (2006) State of the art in hair analysis for detection of drug and alcohol abuse. Clin Chim Acta 370(1–2):17–49

    Article  CAS  Google Scholar 

  2. Wille SMR, Baumgartner MR, Di Fazio V, Samyn N, Kraemer T (2014) Trends in drug testing in oral fluid and hair as alternative matrices. Bioanalysis 6(17):2193–2209

    Article  CAS  Google Scholar 

  3. Cooper G, Kronstrand R, Kintz P (2012) Society of hair testing guidelines for drug testing in hair. Forensic Sci Int 218(1–3):20–24

    Article  CAS  Google Scholar 

  4. Henderson GL, Harkey MR, Zhou C, Jones RT, Jacob P (1996) Incorporation of isotopically labeled cocaine and metabolites into human hair: 1. Dose–response relationships. J Anal Toxicol 20(1):1–12

    Article  CAS  Google Scholar 

  5. Jakobsson G, Kronstrand R (2014) Segmental analysis of amphetamines in hair using a sensitive UHPLC-MS/MS method. Drug Test Anal 6(S1):22–29

    Article  CAS  Google Scholar 

  6. Kintz P (2013) Issues about axial diffusion during segmental hair analysis. Ther Drug Monit 35(3):408–410

    Article  CAS  Google Scholar 

  7. Rothe M, Pragst F, Spiegel K, Harrach T, Fischer K, Kunkel J (1997) Hair concentrations and self-reported abuse history of 20 amphetamine and ecstasy users. Forensic Sci Int 89(1–2):111–128

    Article  CAS  Google Scholar 

  8. Polettini A, Cone EJ, Gorelick DA, Huestis MA (2012) Incorporation of methamphetamine and amphetamine in human hair following controlled oral methamphetamine administration. Anal Chim Acta 726:35–43

    Article  CAS  Google Scholar 

  9. Cappelle D, Yegles M, Neels H, van Nuijs AL, De Doncker M, Maudens K, Covaci A, Crunelle CL (2014) Nail analysis for the detection of drugs of abuse and pharmaceuticals: a review. Forensic Toxicol:1–25

  10. Garside D (2008) Drugs-of-abuse in nails. In: Jenkins AJ (ed) Drug testing in alternate biological specimens. Forensic science and medicine. Humana Press, Totowa, pp 43–65

    Chapter  Google Scholar 

  11. Palmeri A, Pichini S, Pacifici R, Zuccaro P, Lopez A (2000) Drugs in nails - physiology, pharmacokinetics and forensic toxicology. Clin Pharmacokinet 38(2):95–110

    Article  CAS  Google Scholar 

  12. Madry MM, Steuer AE, Vonmoos M, Quednow BB, Baumgartner MR, Kraemer T (2014) Retrospective monitoring of long-term recreational and dependent cocaine use in toenail clippings/scrapings as an alternative to hair. Bioanalysis 6(23):3183–3196

    Article  CAS  Google Scholar 

  13. Krumbiegel F, Hastedt M, Tsokos M (2014) Nails are a potential alternative matrix to hair for drug analysis in general unknown screenings by liquid-chromatography quadrupole time-of-flight mass spectrometry. Forensic Sci Med Pathol:1–8

  14. Morini L, Colucci M, Ruberto M, Groppi A (2012) Determination of ethyl glucuronide in nails by liquid chromatography tandem mass spectrometry as a potential new biomarker for chronic alcohol abuse and binge drinking behavior. Anal Bioanal Chem 402(5):1865–1870

    Article  CAS  Google Scholar 

  15. Liechti ME, Geyer MA, Hell D, Vollenweider FX (2001) Effects of MDMA (ecstasy) on prepulse inhibition and habituation of startle in humans after pretreatment with citalopram, haloperidol, or ketanserin. Neuropsychopharmacology 24(3):240–252

    Article  CAS  Google Scholar 

  16. Fleckman P (1985) Anatomy and physiology of the nail. Dermatol Clin 3(3):373–381

    CAS  Google Scholar 

  17. Yaemsiri S, Hou N, Slining MM, He K (2010) Growth rate of human fingernails and toenails in healthy American young adults. J Eur Acad Dermatol Venereol 24(4):420–423

    Article  CAS  Google Scholar 

  18. Suzuki O, Hattori H, Asano M (1984) Nails as useful materials for detection of methamphetamine or amphetamine abuse. Forensic Sci Int 24(1):9–16

    Article  CAS  Google Scholar 

  19. Lin D-L, Yin R-M, Liu H-C, Wang C-Y, Liu RH (2004) Deposition characteristics of methamphetamine and amphetamine in fingernail clippings and hair sections. J Anal Toxicol 28(6):411–417

    Article  CAS  Google Scholar 

  20. Cirimele V, Kintz P, Mangin P (1995) Detection of amphetamines in fingernails: an alternative to hair analysis. Arch Toxicol 70(1):68–69

    Article  CAS  Google Scholar 

  21. Pötsch L (1996) A discourse on human hair fibers and reflections on the conservation of drug molecules. Int J Legal Med 108(6):285–293

    Article  Google Scholar 

  22. Potsch L, Skopp G, Moeller MR (1997) Biochemical approach on the conservation of drug molecules during hair fiber formation. Paper presented at the Forensic Science International Proceedings of the 1st European Meeting on Hair Analysis. Clinical, Occupational and Forensic Application, 1/17/1997

  23. Henderson GL (1993) Mechanisms of drug incorporation into hair. Forensic Sci Int 63(1–3):19–29

    Article  CAS  Google Scholar 

  24. Hang C, Ping X, Min S (2013) Long-term follow-up analysis of zolpidem in fingernails after a single oral dose. Anal Bioanal Chem 405(23):7281–7289

    Article  CAS  Google Scholar 

  25. Madry MM, Steuer AE, Binz TM, Baumgartner MR, Kraemer T (2014) Systematic investigation of the incorporation mechanisms of zolpidem in fingernails. Drug Test Anal 6(6):533–541

    Article  CAS  Google Scholar 

  26. Rentsch KM (2002) The importance of stereoselective determination of drugs in the clinical laboratory. J Biochem Biophys Methods 54(1):1–9

    Article  CAS  Google Scholar 

  27. European Monitoring Centre for Drugs and Drug Addiction (EMCDDA) (2015) Methylenedioxymethamphetamine (MDMA or ‘Ecstasy’) drug profile. http://www.emcdda.europa.eu/publications/drug-profiles/mdma

  28. Pilgrim JL, Gerostamoulos D, Drummer OH (2011) Deaths involving MDMA and the concomitant use of pharmaceutical drugs. J Anal Toxicol 35(4):219–226

    Article  CAS  Google Scholar 

  29. Milroy CM (2011) “Ecstasy” associated deaths: what is a fatal concentration? Analysis of a case series. Forensic Sci Med Pathol 7(3):248–252

    Article  CAS  Google Scholar 

  30. Senna MC, Augsburger M, Aebi B, Briellmann TA, Donze N, Dubugnon JL, Iten PX, Staub C, Sturm W, Sutter K (2010) First nationwide study on driving under the influence of drugs in Switzerland. Forensic Sci Int 198(1–3):11–16

    Article  CAS  Google Scholar 

  31. Schifano F, Corkery J, Deluca P, Oyefeso A, Ghodse AH (2006) Ecstasy (MDMA, MDA, MDEA, MBDB) consumption, seizures, related offences, prices, dosage levels and deaths in the UK (1994–2003). J Psychopharmacol 20(3):456–463

    Article  Google Scholar 

  32. Liechti M (2015) Novel psychoactive substances (designer drugs): overview and pharmacology of modulators of monoamine signalling. Swiss Med Wkly 145:w14043

    Google Scholar 

  33. Green AR, Mechan AO, Elliott JM, O’Shea E, Colado MI (2003) The pharmacology and clinical pharmacology of 3,4-methylenedioxymethamphetamine (MDMA, “ecstasy”). Pharmacol Rev 55(3):463–508

    Article  CAS  Google Scholar 

  34. de la Torre R, Farre M, Roset PN, Pizarro N, Abanades S, Segura M, Segura J, Cami J (2004) Human pharmacology of MDMA: pharmacokinetics, metabolism, and disposition [review]. Ther Drug Monit 26(2):137–144

    Article  Google Scholar 

  35. Schwaninger AE, Meyer MR, Barnes AJ, Kolbrich-Spargo EA, Gorelick DA, Goodwin RS, Huestis MA, Maurer HH (2012) Stereoselective urinary MDMA (ecstasy) and metabolites excretion kinetics following controlled MDMA administration to humans. Biochem Pharmacol 83(1):131–138

    Article  CAS  Google Scholar 

  36. Fallon JK, Kicman AT, Henry JA, Milligan PJ, Cowan DA, Hutt AJ (1999) Stereospecific analysis and enantiomeric disposition of 3, 4-methylenedioxymethamphetamine (Ecstasy) in humans. Clin Chem 45(7):1058–1069

    CAS  Google Scholar 

  37. Peters FT, Samyn N, Wahl M, Kraemer T, de Boeck G, Maurer HH (2003) Concentrations and ratios of amphetamine, methamphetamine, MDA, MDMA, and MDEA enantiomers determined in plasma samples from clinical toxicology and driving under the influence of drugs cases by GC-NICI-MS. J Anal Toxicol 27(8):552–559

    Article  CAS  Google Scholar 

  38. Moore KA, Mozayani A, Fierro MF, Poklis A (1996) Distribution of 3,4-methylenedioxymethamphetamine (MDMA) and 3,4-methylenedioxyamphetamine (MDA) stereoisomers in a fatal poisoning. Forensic Sci Int 83(2):111–119

    Article  CAS  Google Scholar 

  39. de la Torre R, Farre M, Ortuno J, Mas M, Brenneisen R, Roset PN, Segura J, Cami J (2000) Non-linear pharmacokinetics of MDMA (‘ecstasy’) in humans. Br J Clin Pharmacol 49(2):104–109

    Article  Google Scholar 

  40. Sachse C, Brockmöller J, Bauer S, Roots I (1997) Cytochrome P450 2D6 variants in a Caucasian population: allele frequencies and phenotypic consequences. Am J Hum Genet 60(2):284–295

    CAS  Google Scholar 

  41. Steuer AE, Schmidhauser C, Schmid Y, Rickli A, Liechti ME, Kraemer T (2015) Chiral plasma pharmacokinetics of 3,4-methylenedioxymethamphetamine (MDMA) and its phase I and II metabolites following controlled administrations to humans. Drug Metab Dispos (accepted)

  42. Hysek CM, Simmler LD, Schillinger N, Meyer N, Schmid Y, Donzelli M, Grouzmann E, Liechti ME (2014) Pharmacokinetic and pharmacodynamic effects of methylphenidate and MDMA administered alone or in combination. Int J Neuropsychopharmacol 17(3):371–381

    Article  CAS  Google Scholar 

  43. Steuer AE, Schmidhauser C, Liechti ME, Kraemer T (2015) Development and validation of an LC-MS/MS method after chiral derivatization for the simultaneous stereoselective determination of methylenedioxy-methamphetamine (MDMA) and its phase I and II metabolites in human blood plasma. Drug Test Anal 7(7):592–602

    Article  CAS  Google Scholar 

  44. Nakanishi K, Katagi M, Zaitsu K, Shima N, Kamata H, Miki A, Kato H, Harada KI, Tsuchihashi H, Suzuki K (2012) Simultaneous enantiomeric determination of MDMA and its phase I and phase II metabolites in urine by liquid chromatography-tandem mass spectrometry with chiral derivatization. Anal Bioanal Chem 404(8):2427–2435

    Article  CAS  Google Scholar 

  45. Matuszewski BK, Constanzer ML, Chavez-Eng CM (2003) Strategies for the assessment of matrix effect in quantitative bioanalytical methods based on HPLC-MS/MS. Anal Chem 75(13):3019–3030

    Article  CAS  Google Scholar 

  46. Musshoff F, Skopp G, Pragst F, Sachs H (2009) Appendix C of the GTFCh guidelines for quality control in forensic-toxicological analyses. Quality requirements for the analysis of hair samples

  47. Mieczkowski T, Newel R (2000) Statistical examination of hair color as a potential biasing factor in hair analysis. Forensic Sci Int 107(1–3):13–38

    Article  CAS  Google Scholar 

  48. Martins LF, Yegles M, Samyn N, Ramaekers JG, Wennig R (2007) Time-resolved hair analysis of MDMA enantiomers by GC/MS-NCI. Forensic Sci Int 172(2–3):150–155

    Article  CAS  Google Scholar 

  49. Strano-Rossi S, Botrè F, Bermejo AM, Tabernero MJ (2009) A rapid method for the extraction, enantiomeric separation and quantification of amphetamines in hair. Forensic Sci Int 193(1–3):95–100

    Article  CAS  Google Scholar 

  50. Tagliaro F, Manetto G, Bellini S, Scarcella D, Smith FP, Marigo M (1998) Simultaneous chiral separation of 3,4-methylenedioxymethamphet- amine, 3-4-methylenedioxyamphetamine, 3,4-methylenedioxyethylam- phetamine, ephedrine, amphetamine and methamphetamine by capillary electrophoresis in uncoated and coated capillaries with native beta-cyclodextrin as the chiral selector: preliminary application to the analysis of urine and hair. Electrophoresis 19(1):42–50

    Article  CAS  Google Scholar 

  51. Society of Hair Testing (1997) Statement of the Society of Hair Testing concerning the examination of drugs in human hair. Forensic Sci Int 84:3–6

    Article  Google Scholar 

  52. Romano G, Barbera N, Spadaro G, Valenti V (2003) Determination of drugs of abuse in hair: evaluation of external heroin contamination and risk of false positives. Forensic Sci Int 131(2–3):98–102

    Article  CAS  Google Scholar 

  53. Madry MM, Rust KY, Guglielmello R, Baumgartner MR, Kraemer T (2012) Metabolite to parent drug concentration ratios in hair for the differentiation of tramadol intake from external contamination and passive exposure. Forensic Sci Int 223(1–3):330–334

    Article  CAS  Google Scholar 

  54. Romano G, Barbera N, Lombardo I (2001) Hair testing for drugs of abuse: evaluation of external cocaine contamination and risk of false positives. Forensic Sci Int 123(2–3):119–129

    Article  CAS  Google Scholar 

  55. Cooper G, Allen DL, Scott KS, Oliver JS, Ditton J, Smith ID (2000) Hair analysis: self-reported use of “speed” and “ecstasy” compared with laboratory findings. J Forensic Sci 45(2):400–406

    Article  CAS  Google Scholar 

  56. Pichini S, Poudevida S, Pujadas M, Menoyo E, Pacifici R, Farré M, de la Torre R (2006) Assessment of chronic exposure to MDMA in a group of consumers by segmental hair analysis. Ther Drug Monit 28(1):106–109

    Article  CAS  Google Scholar 

Download references

Acknowledgments

The study was supported by the Swiss National Science Foundation (No 320030_149493/1 to MEL) and the Emma Louise Kessler Fonds of the Zurich Institute of Forensic Medicine.

Author information

Authors and Affiliations

  1. Zurich Institute of Forensic Medicine, Center for Forensic Hairanalytics, University of Zurich, Winterthurerstrasse 190, 8057, Zurich, Switzerland

    Milena M. Madry & Markus R. Baumgartner

  2. Zurich Institute of Forensic Medicine, Forensic Pharmacology and Toxicology, University of Zurich, Winterthurerstrasse 190/52, 8057, Zurich, Switzerland

    Andrea E. Steuer & Thomas Kraemer

  3. Psychopharmacology Research, Division of Clinical Pharmacology and Toxicology, Department of Biomedicine and Department of Clinical Research, University Hospital Basel, Hebelstrasse 2, 4031, Basel, Switzerland

    Cédric M. Hysek & Matthias E. Liechti

Authors
  1. Milena M. Madry
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Andrea E. Steuer
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Cédric M. Hysek
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Matthias E. Liechti
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Markus R. Baumgartner
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Thomas Kraemer
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Thomas Kraemer.

Ethics declarations

Conflict of interest

The authors declare no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Madry, M.M., Steuer, A.E., Hysek, C.M. et al. Evaluation of drug incorporation into hair segments and nails by enantiomeric analysis following controlled single MDMA intakes. Anal Bioanal Chem 408, 545–556 (2016). https://doi.org/10.1007/s00216-015-9130-3

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00216-015-9130-3

Keywords

Search

Navigation