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Development of a chemometric method in urine sample for newly designed hallucinating psychoactive substances: 5-MeO-MiPT

Year 2023, , 355 - 363, 18.09.2023
https://doi.org/10.19161/etd.1360340

Abstract

Aim: In this study, a method was developed for analysis and chemometric optimization for 5-methoxy-N-methyl-N-isopropyltryptamine (5-MeO-MiPT).
Materials and Methods: Our study was carried out in Ege University Institute on Drug Abuse, Toxicology and Pharmaceutical Science, Addiction Toxicology Laboratory.
Analysis and optimization of the effects of hydrolysis and solid phase extraction processes during the analysis of 5-MeO-MiPT by Gas Chromatography-Mass Spectrometry (GC-MS). For chemometric screenings design, Plackett-Burman was used. The most effective three factors were determined, and a central composite design was applied, and results were evaluated with surface response methodology. The method was validated for selectivity, linearity, the limit of detection, the limit of quantitation, accuracy, intra-day and inter-day repeatability, stability and carry over.
Results: In the chemometric method, the most effective parameters were found sample volume, hydrolysis temperature, and elution volume for 5-MeO-MiPT in urine analysis. Optimum values for these parameters were calculated by surface response methodology and the results were determined 1ml urine volume, 30°C hydrolysis temperature, 3,5 ml elution volume, respectively. The optimized method was validated for selectivity, linearity (25-500 ng/mL), limit of detection (5 ng/mL), limit of quantitation (18 ng/mL), accuracy (72-101%), intra-day and inter-day precisions were measured, respectively (4,43% RSD),(4,27% CV), stability and carry over parameters.
Conclusion: With a chemometric approach, quick, practical and accurate method for the detection of 5-MeO-MiPT has been developed with GC-MS. Working of 5-MeO-MiPT without derivatization in GC-MS analysis has shortened the pre-preparation time and is a pioneer for other analogs. It provides an effective method in the analysis of substances such as synthetic analogues from tryptamines which are added every day, with the use of such classical equipment and new methods.

References

  • Fabregat-Safont D, Barneo-Muñoz M, Martinez-Garcia F, Sancho J V., Hernández F, Ibáñez M. Proposal of 5-methoxy-N-methyl-N-isopropyltryptamine consumption biomarkers through identification of in vivo metabolites from mice. J Chromatogr A. 2017;1508:95–105.
  • UNODC. Early Warning Advisory on new psychoactive substances. 2020: 1-3 p.
  • EMCDDA. EU Drug Markets Report 2019. 2019. 260 p.
  • Grafinger KE, Hädener M, König S, Weinmann W. Study of the in vitro and in vivo metabolism of the tryptamine 5-MeO-MiPT using human liver microsomes and real case samples. Drug Test Anal. 2018;10(3):562–74.
  • Shulgin A. TIHKAL - Tryptamines i Have Known And Loved : The Chemistry Continues [Internet]. Transform press.; 1997. 804 p. Available from: https://www.thevespiary.org/rhodium/Rhodium/hive/hiveboard/picproxie_docs/000532880-Alexander_Shulgin_and_Ann_Shulgin_-_TiHKAL.pdf
  • Meyer MR, Caspar A, Brandt SD, Maurer HH. A qualitative/quantitative approach for the detection of 37 tryptamine-derived designer drugs, 5 β-carbolines, ibogaine, and yohimbine in human urine and plasma using standard urine screening and multi-analyte approaches. Anal Bioanal Chem. 2014;406(1).
  • Araújo AM, Carvalho F, Bastos M de L, Guedes de Pinho P, Carvalho M. The hallucinogenic world of tryptamines: an updated review. Arch Toxicol. 2015;89(8):1151–73.
  • Göl E, Çok I. New psychoactive substances in Turkey: Narcotics cases assessed by the Council of Forensic Medicine between 2016 and 2017 in Ankara, Turkey. Forensic Sci Int. 2019;294.
  • Kumar R, Sharma V. Chemometrics in forensic science. Vol. 105, TrAC - Trends in Analytical Chemistry. 2018: 191-201 p.
  • Bezerra MA, Santelli RE, Oliveira EP, Villar LS, Escaleira LA. Response surface methodology (RSM) as a tool for optimization in analytical chemistry. Talanta. 2008 Sep 15;76(5):965–77.
  • Haglock-Adler CJ, Hurley A, Strathmann FG. Use of synthetic urine as a matrix substitute for standard and quality control materials in the clinical assessment of iodine by inductively coupled plasma mass spectrometry. Clin Biochem. 2014 Dec 1;47(15):80–2.
  • United Nations Office on Drugs and Crime (UNODC). The Challenge of New Psychoactive Substances - Global SMART Programme [Internet]. 2013 [cited 2021 Mar 9]. Available from: https://www.unodc.org/unodc/en/scientists/the-challenge-of-new-psychoactive-substances---global-smart-programme.html
  • Kelly K, Bell S. Evaluation of the reproducibility and repeatability of GCMS retention indices and mass spectra of novel psychoactive substances. Forensic Chem. 2018 Mar 1;7:10–8.
  • Zacca JJ, Giudice GH, Souza MP, Caldas LNB, Vieira ML, Machado AHL. Development and validation of analytical method for identification of new psychoactive substances using linear retention indexes and gas chromatography-mass spectrometry. J Chromatogr A. 2021 Jan 11;1636:461783.
  • Grafinger KE, Hädener M, König S, Weinmann W. Study of the in vitro and in vivo metabolism of the tryptamine 5-MeO-MiPT using human liver microsomes and real case samples. Drug Test Anal. 2017;(June):1–13.
  • Fantegrossi WE, Harrington AW, Kiessel CL, Eckler JR, Rabin RA, Winter JC, et al. Hallucinogen-like actions of 5-methoxy-N,N-diisopropyltryptamine in mice and rats. Pharmacol Biochem Behav. 2006;83(1).
  • Altuncı YA, Aydoğdu M, Açıkgöz E, Güven Ü, Duzağa F, Atasoy A, et al. New Psychoactive Substance 5-MeO-MIPT In vivo Acute Toxicity and Hystotoxicological Study. Balkan Med J. 2020; 34-42 p.
  • Shimizu E, Watanabe H, Kojima T, Hagiwara H, Fujisaki M, Miyatake R, et al. Combined intoxication with methylone and 5-MeO-MIPT. Prog Neuro-Psychopharmacology Biol Psychiatry. 2007;31(1):288–91.
  • Wilson JM, McGeorge F, Smolinske S, Meatherall R. A foxy intoxication. Forensic Sci Int. 2005;148(1).
  • Kamata T, Katagi M, Kamata HT, Miki A, Shima N, Zaitsu K, et al. Metabolism of the psychotomimetic tryptamine derivative 5-methoxy-N, N-diisopropyltryptamine in humans: Identification and quantification of its urinary metabolites. Drug Metab Dispos. 2006;34(2): 281-287
  • Yan X, Xiang P, Zhao Y, Yu Z, Yan H. Determination of 5-MeO-DIPT in Human Urine Using Gas Chromatography Coupled with High-Resolution Orbitrap Mass Spectrometry. J Anal Toxicol. 2020;44(5):461–469.
  • Caspar AT, Gaab JB, Michely JA, Brandt SD, Meyer MR, Maurer HH. Metabolism of the tryptamine-derived new psychoactive substances 5-MeO-2-Me-DALT, 5-MeO-2-Me-ALCHT, and 5-MeO-2-Me-DIPT and their detectability in urine studied by GC–MS, LC–MS, and LC-HR-MS/MS. Drug Test Anal. 2018;10(1):184–95.
  • Yan X, Yuan S, Yu Z, Zhao Y, Zhang S, Wu H, et al. Development of an LC-MS/MS method for determining 5-MeO-DIPT in dried urine spots and application to forensic cases. J Forensic Leg Med. 2020;72.
  • Shi Y, Wang R, Yuan S, Qiang H, Shen M, Shen B, et al. UHPLC-MS/MS method for simultaneously detecting 16 tryptamines and their metabolites in human hair and applications to real forensics cases. J Chromatogr B Anal Technol Biomed Life Sci. 2020 Nov 30;1159:122392.

Halüsinasyon yapan yeni tasarım psikoaktif maddelerden biri olan 5-MeO-MiPTin idrarda tayinine yönelik kemometrik yöntem geliştirilmesi

Year 2023, , 355 - 363, 18.09.2023
https://doi.org/10.19161/etd.1360340

Abstract

Amaç: Bu çalışmada yeni psikoaktif maddelerden biri olan 5-metoksi-N-metil-N-izopropiltriptamin (5-MeO-MiPT) için analiz ve kemometrik optimizasyon için bir yöntem geliştirmeyi amaçladık.
Gereç ve Yöntem: Çalışmamız Ege Üniversitesi Madde Bağımlılığı, Toksikoloji ve İlaç Bilimleri Enstitüsü Bağımlılık Toksikolojisi Laboratuvarında gerçekleşmiştir. 5-MeO-MiPT'nin Gaz Kromatografi-Kütle Spektrometrisi (GC-MS) ile analizi sırasında hidroliz ve katı faz ekstraksiyon işlemlerinin etkileri incelendi ve optimizasyonu yapıldı. Kemometrik tarama tasarımı için Plackett-Burman kullanıldı. En etkili üç faktör belirlenerek merkezi bir kompozit tasarım uygulandı ve sonuçlar yüzey tepki metodolojisi ile değerlendirildi. Yöntem, seçicilik, doğrusallık, tespit limiti, miktar tayini limiti, doğruluk, gün içi ve günler-arası tekrarlanabilirlik, stabilite ve taşıma arasında valide edildi.
Bulgular: Kemometrik yöntemde, idrar analizinde 5-MeO-MiPT için en etkili parametreler numune hacmi, hidroliz sıcaklığı ve elüsyon hacmi bulundu. Bu parametreler için optimum değerler yüzey tepki metodolojisi ile hesaplandı ve sonuçlar sırasıyla 1 ml idrar hacmi, 30°C hidroliz sıcaklığı, 3,5 ml elüsyon hacmi olarak belirlendi. Optimize edilmiş yöntem seçicilik, doğrusallık (25-500ng/mL), belirtme alt limiti (5,63 ng/mL), tayin alt limiti 18,75 ng/mL), doğruluk (%43,01-%101,47), gün içi tekrarlanabilirlik ( 100 ng/ml derişimde 3 paralel, %RSD 4,43),günler-arası tekrarlanabilirlik (100 ng/ml derişimde 5 farklı gün 3 tekrarda, %CV 4,27), seyreltme tamlığı, taşınma etkisi ve kararlılık parametreleri incelenmiştir.
Sonuç: Kemometrik bir yaklaşımla, GC-MS ile 5-MeO-MiPT tespiti için hızlı, pratik ve doğru bir yöntem geliştirildi. 5-MeO-MiPT'nin GC-MS analizinde türevlendirilmeden çalışması, ön hazırlık süresini kısaltmış ve diğer analoglar için öncü olmuştur. Her gün eklenen triptaminlerin sentetik analogları gibi maddelerin analizinde bu tür klasik cihazlar/sistemler ve yeni yöntemler ile etkin bir yöntem sağlar.

References

  • Fabregat-Safont D, Barneo-Muñoz M, Martinez-Garcia F, Sancho J V., Hernández F, Ibáñez M. Proposal of 5-methoxy-N-methyl-N-isopropyltryptamine consumption biomarkers through identification of in vivo metabolites from mice. J Chromatogr A. 2017;1508:95–105.
  • UNODC. Early Warning Advisory on new psychoactive substances. 2020: 1-3 p.
  • EMCDDA. EU Drug Markets Report 2019. 2019. 260 p.
  • Grafinger KE, Hädener M, König S, Weinmann W. Study of the in vitro and in vivo metabolism of the tryptamine 5-MeO-MiPT using human liver microsomes and real case samples. Drug Test Anal. 2018;10(3):562–74.
  • Shulgin A. TIHKAL - Tryptamines i Have Known And Loved : The Chemistry Continues [Internet]. Transform press.; 1997. 804 p. Available from: https://www.thevespiary.org/rhodium/Rhodium/hive/hiveboard/picproxie_docs/000532880-Alexander_Shulgin_and_Ann_Shulgin_-_TiHKAL.pdf
  • Meyer MR, Caspar A, Brandt SD, Maurer HH. A qualitative/quantitative approach for the detection of 37 tryptamine-derived designer drugs, 5 β-carbolines, ibogaine, and yohimbine in human urine and plasma using standard urine screening and multi-analyte approaches. Anal Bioanal Chem. 2014;406(1).
  • Araújo AM, Carvalho F, Bastos M de L, Guedes de Pinho P, Carvalho M. The hallucinogenic world of tryptamines: an updated review. Arch Toxicol. 2015;89(8):1151–73.
  • Göl E, Çok I. New psychoactive substances in Turkey: Narcotics cases assessed by the Council of Forensic Medicine between 2016 and 2017 in Ankara, Turkey. Forensic Sci Int. 2019;294.
  • Kumar R, Sharma V. Chemometrics in forensic science. Vol. 105, TrAC - Trends in Analytical Chemistry. 2018: 191-201 p.
  • Bezerra MA, Santelli RE, Oliveira EP, Villar LS, Escaleira LA. Response surface methodology (RSM) as a tool for optimization in analytical chemistry. Talanta. 2008 Sep 15;76(5):965–77.
  • Haglock-Adler CJ, Hurley A, Strathmann FG. Use of synthetic urine as a matrix substitute for standard and quality control materials in the clinical assessment of iodine by inductively coupled plasma mass spectrometry. Clin Biochem. 2014 Dec 1;47(15):80–2.
  • United Nations Office on Drugs and Crime (UNODC). The Challenge of New Psychoactive Substances - Global SMART Programme [Internet]. 2013 [cited 2021 Mar 9]. Available from: https://www.unodc.org/unodc/en/scientists/the-challenge-of-new-psychoactive-substances---global-smart-programme.html
  • Kelly K, Bell S. Evaluation of the reproducibility and repeatability of GCMS retention indices and mass spectra of novel psychoactive substances. Forensic Chem. 2018 Mar 1;7:10–8.
  • Zacca JJ, Giudice GH, Souza MP, Caldas LNB, Vieira ML, Machado AHL. Development and validation of analytical method for identification of new psychoactive substances using linear retention indexes and gas chromatography-mass spectrometry. J Chromatogr A. 2021 Jan 11;1636:461783.
  • Grafinger KE, Hädener M, König S, Weinmann W. Study of the in vitro and in vivo metabolism of the tryptamine 5-MeO-MiPT using human liver microsomes and real case samples. Drug Test Anal. 2017;(June):1–13.
  • Fantegrossi WE, Harrington AW, Kiessel CL, Eckler JR, Rabin RA, Winter JC, et al. Hallucinogen-like actions of 5-methoxy-N,N-diisopropyltryptamine in mice and rats. Pharmacol Biochem Behav. 2006;83(1).
  • Altuncı YA, Aydoğdu M, Açıkgöz E, Güven Ü, Duzağa F, Atasoy A, et al. New Psychoactive Substance 5-MeO-MIPT In vivo Acute Toxicity and Hystotoxicological Study. Balkan Med J. 2020; 34-42 p.
  • Shimizu E, Watanabe H, Kojima T, Hagiwara H, Fujisaki M, Miyatake R, et al. Combined intoxication with methylone and 5-MeO-MIPT. Prog Neuro-Psychopharmacology Biol Psychiatry. 2007;31(1):288–91.
  • Wilson JM, McGeorge F, Smolinske S, Meatherall R. A foxy intoxication. Forensic Sci Int. 2005;148(1).
  • Kamata T, Katagi M, Kamata HT, Miki A, Shima N, Zaitsu K, et al. Metabolism of the psychotomimetic tryptamine derivative 5-methoxy-N, N-diisopropyltryptamine in humans: Identification and quantification of its urinary metabolites. Drug Metab Dispos. 2006;34(2): 281-287
  • Yan X, Xiang P, Zhao Y, Yu Z, Yan H. Determination of 5-MeO-DIPT in Human Urine Using Gas Chromatography Coupled with High-Resolution Orbitrap Mass Spectrometry. J Anal Toxicol. 2020;44(5):461–469.
  • Caspar AT, Gaab JB, Michely JA, Brandt SD, Meyer MR, Maurer HH. Metabolism of the tryptamine-derived new psychoactive substances 5-MeO-2-Me-DALT, 5-MeO-2-Me-ALCHT, and 5-MeO-2-Me-DIPT and their detectability in urine studied by GC–MS, LC–MS, and LC-HR-MS/MS. Drug Test Anal. 2018;10(1):184–95.
  • Yan X, Yuan S, Yu Z, Zhao Y, Zhang S, Wu H, et al. Development of an LC-MS/MS method for determining 5-MeO-DIPT in dried urine spots and application to forensic cases. J Forensic Leg Med. 2020;72.
  • Shi Y, Wang R, Yuan S, Qiang H, Shen M, Shen B, et al. UHPLC-MS/MS method for simultaneously detecting 16 tryptamines and their metabolites in human hair and applications to real forensics cases. J Chromatogr B Anal Technol Biomed Life Sci. 2020 Nov 30;1159:122392.
There are 24 citations in total.

Details

Primary Language English
Subjects Subtance Abuse
Journal Section Research Articles
Authors

Ezgi Emen 0000-0002-4598-5080

Rukiye Aslan 0000-0002-4012-3684

Melike Aydoğdu 0000-0002-6324-0234

Hasan Ertaş 0000-0002-5539-3732

Serap Annette Akgür 0000-0001-9638-2311

Publication Date September 18, 2023
Submission Date May 23, 2022
Published in Issue Year 2023

Cite

Vancouver Emen E, Aslan R, Aydoğdu M, Ertaş H, Annette Akgür S. Development of a chemometric method in urine sample for newly designed hallucinating psychoactive substances: 5-MeO-MiPT. ETD. 2023;62(3):355-63.

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