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2022, Number 3

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Rev Cubana Farm 2022; 55 (3)

Strategies for identifying amphetamine and methamphetamine derivatives in urine by gas chromatography-mass spectrometry

McPherson MA, Martínez BD, Torres CM, Fiallo FT, Correa VT, Montes de Oca PR

Language: Spanish
References: 21
Page: 1-19
PDF size: 1191.83 Kb.


ABSTRACT

Introduction: One of the challenges in doping control analysis is to demonstrate the preciseness and accuracy of the analytical results. Therefore, it is necessary to show evidence during the analysis of the samples about what exactly the athlete consumed. Selegiline is a stimulant substance synthesized from levo-methamphetamine. Its fundamental metabolites are L-amphetamine and L-methamphetamine which are also metabolites of other substances.
Objective: To evaluate the formation of derivatives in the analysis of amphetamine and methamphetamine through three chromatographic parameters to establish a strategy for the identification of both compounds.
Methods: Urine samples collected before and after oral administration of 10 mg of selegiline were evaluated to verify the functionality of the methods. After a liquid-liquid extraction with tert-butyl methylether at alkaline pH, R-α-methoxy-α-(trifluoromethyl)-phenylacetyl (R-MTPCl) and N-trifluoroacetamide (TFA) derivatives were obtained for analysis by gas chromatography-mass spectrometry. The outcomes without and with formation of N-TFA and R-MTPCl derivatives were compared.
Results: N-TFA derivatives proved not to be a good option in quantification trials due to the formation of multiple derivatives. However, its application in identification processes (like the derivative R-MTPCl) allowed the obtention of fragments of high diagnostic value in the mass spectrum. After elimination of specific metabolites of selegiline, only amphetamine and methamphetamine were observed. The use of the derivative R-MTPCl chromatographically resolved the levo and dextro enantiomers of both compounds.
Conclusions: The evaluation of samples containing amphetamine and methamphetamine- N-TFA allowed to obtain mass spectra with high diagnostic value, but it is not recommended in quantification tests. The use of the R-MTPCl reagent increased the accuracy in the identification of the original selegiline drug.


REFERENCES

  1. World-Anti Doping Agency (WADA). Prohibited List 2022. Montreal, Canadá: WADA;

  2. 2022 [acceso 27/01/2022]. Disponible en: https://www.wada-ama.org/en/resources2. Thevis M, Sigmund G, Geyer H, Schänzer W. Stimulants and Doping in Sport. EndocrinolMetab Clin North Am. 2010;39(1):89-105. DOI: 10.1016/j.ecl.2009.10.011

  3. Musshoff F. Illegal or legitimate use? Precursor compounds to amphetamine andmethamphetamine. Drug Metab Rev. 2000;32(1):15-44. DOI: 10.1081/DMR-100100562

  4. Wang SM, Wang TC, Giang YS. Simultaneous determination of amphetamine andmethamphetamine enantiomers in urine by simultaneous liquid-liquid extraction anddiastereomeric derivatization followed by gas chromatographic-isotope dilution massspectrometry. J Chromatogr B Anal Technol Biomed Life Sci. 2005;816(1-2):131-43. DOI:10.1016/j.jchromb.2004.11.027

  5. Rosano TG, Ohouo PY, Wood M. Screening with quantification for 64 drugs andmetabolites in human urine using UPLC-MS-MS analysis and a threshold accuratecalibration. J Anal Toxicol. 2017;41(6):536-46. DOI: 10.1093/jat/bkx035

  6. Segawa HT, Iwata Y, Yamamuro T, Kuwayama K, Tsujikawa K, Kanamori T, et al.Differentiation of ring-substituted regioisomers of amphetamine and methamphetamine bysupercritical fluid chromatography. Drug Test Anal. 2017;9(3):389-98. DOI:10.1002/dta.2040

  7. Moldoveanu SC, David V. Gas Chromatography - Derivatization, Sample Preparation,Application. Chapter 3 Derivatization Methods in GC and GC/MS. Intechopen; 2018. p. 33[acceso 27/01/2022].DOI: 10.5772/intechopen.81954

  8. Kranenburg RF, Verduin J, Stuyver LI, de Ridder R, van Beek A, Colmsee E, et al.Benefits of derivatization in GC–MS-based identification of new psychoactive substances.Forensic Chem. 2020;20(August):100273. DOI: 10.1016/j.forc.2020.100273

  9. Beale DJ, Pinu FR, Kouremenos KA, Poojary MM, Narayana VK, Boughton BA, et al.Review of recent developments in GC–MS approaches to metabolomics-based research.Metabolomics. 2018;14(152):1-31. DOI: 10.1007/s11306-018-1449-2

  10. Macherone A. A Brief Review of Derivatization Chemistries for the Analysis ofCannabinoids Using GC–MS. Cannabis Sci Technol. 2020;3(7):42-8 [acceso 27/01/2022].Disponible en:https://cdn.sanity.io/files/0vv8moc6/cnst/26d280d85604be9922f622e3f5e9fb3d9ed91ea0.pdf

  11. Segura J, Ventura R, Jurado C. Derivatization procedures for gas chromatographic-massspectrometric determination of xenobiotics in biological samples, with special attention todrugs of abuse and doping agents. Journal of Chromatography B. 1998(713:1):61-90. DOI:10.1016/S0378-4347(98)00089-9

  12. Wan-Aasim RW, Gan SH, Tan SC. Development of a simultaneous liquid–liquidextraction and chiral derivatization method for stereospecific GC-MS analysis ofamphetamine-type stimulants in human urine using fractional factorial design. BiomedChromatogr. 2008;22:1035-42. DOI: 10.1002/bmc.1073

  13. 13.Wehrle RJ, Powell DR, Masterson DS. Direct determination of absolute stereochemistryof α-methylselenocysteine using the Mosher method. Results Chem.2021;3(January):100114. DOI: 10.1016/j.rechem.2021.100114

  14. Saito F, Schreiner PR. Determination of the Absolute Configurations of Chiral Alkanes.An Analysis of the Available Tools. European J Org Chem. 2020;(40):6328-39. DOI:10.1002/ejoc.202000711

  15. Boyd RK, Basic C, Bethem RA. Trace Quantitative Analysis by Mass Spectrometry.England: Trace Quantitative Analysis by Mass Spectrometry; New Jersey: John Wiley &Sons Ltd.; 2008.

  16. World Anti-Doping Agency (WADA). Technical Document TD2021IDCR - Minimumcriteria for chromatographic-mass spectrometric confirmation of the identity of analytes fordoping control purposes. Montreal, Canadá: WADA; 2021. [acceso 27/01/2022].https://www.wada-ama.org/en/resources/lab-documents/td2021idcr

  17. Magyar K, Szende B, Jenei V, Tábi T, Pálfi M, Szöko É. R-deprenyl: Pharmacologicalspectrum of its activity. Neurochem Res. 2010;35(12):1922-32. DOI: 10.1007/s11064-010-0238-8

  18. Hasegawa M, Matsubara K, Fukushima S, Maseda C, Uezono T, Kimura K.Stereoselective analyses of selegiline metabolites: Possible urinary markers for selegilinetherapy. Forensic Sci Int. 1999;101(2):95-106. DOI: 10.1016/S0379-0738(99)00015-8

  19. World Medical Association Declaration of Helsinki: ethical principles for medicalresearch involving human subjects. General Principles. J Am Coll Dent. 2014;81(3):14-8.DOI: 10.1093/acprof:oso/9780199241323.003.0025

  20. World Anti-Doping Agency (WADA). WADA Technical Document – TD2022DLDecision limits for the confirmatory quantification of exogenous threshold substances bychromatography-based. Montreal, Canadá: WADA; 2022. [acceso 27/01/2022]. Disponibleen: https://www.wada-ama.org/en/resources/lab-documents/td2022dl

  21. Thevis M. Mass Spectrometry in Sports Drug Testing. Characterization of ProhibitedSubstances and Doping Control Analytical Assays. New Jersey: John Wiley & Sons, Inc.;2010.




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