Simultaneous analysis of mitragynine, 7-hydroxymitragynine, and other alkaloids in the psychotropic plant “kratom” (Mitragyna speciosa) by LC-ESI-MS

Abstract

The leaves of Mitragyna speciosa, a tropical plant known as “kratom,” have been traditionally used as a substitute for opium in Thailand and Malaysia. Mitragynine, a major constituent of M. speciosa, has an opioid agonistic activity, and its derivative 7-hydroxymitragynine (7-OH-mitragynine) (a minor constituent) is much more potent than mitragynine or morphine. Recently, many products containing this plant have been distributed as “incense” on the drug market in Japan for their expected narcotic effects. Despite their potency and their wide distribution for abuse, there are no reports on the quantitative analysis of mitragynine and 7-OH-mitragynine in the raw materials or in the commercial products of kratom. In this study, a method for simultaneous analysis of mitragynine, 7-OH-mitragynine, and other indole alkaloids (speciogynine, speciociliatine, and paynantheine), present in the raw materials and commercial products of kratom, was developed using liquid chromatography-electrospray ionization mass spectrometry (LC-ESI-MS). By this method, mitragynine, 7-OH-mitragynine, and the other alkaloids were detected in 11 of the 13 products. The content of mitragynine in the products ranged from 1% to 6%, and that of 7-OH-mitragynine from 0.01% to 0.04%. Because 7-OH-mitragynine is much more potent than morphine, M. speciosa abuse is a matter of major concern. The present analytical method is considered useful for the screening of M. speciosa products in the drug market.

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

References

  1. 1.

    Kikura-Hanajiri R, Hayashi M, Saisho K, Goda Y (2005). Simultaneous determination of 19 hallucinogenic tryptamines/β-calbolines and phenethylamines using GC-MS and LC-ESIMS. J Chromatogr B 825:29–37

    Article  CAS  Google Scholar 

  2. 2.

    Kikura-Hanajiri R, Kawamura M, Uchiyama N, Ogata J, Kamakura H, Saisho K, Goda Y (2008). Analytical data of designated substances (Shitei-Yakubutsu) controlled by the Pharmaceutical Affairs Law in Japan, part I: GC-MS and LC-MS. Yakugaku Zasshi 128:971–979

    PubMed  Article  CAS  Google Scholar 

  3. 3.

    Uchiyama N, Kawamura M, Kamakura H, Kikura-Hanajiri R, Goda Y (2008). Analytical data of designated substances (Shitei-Yakubutsu) controlled by the Pharmaceutical Affairs Law in Japan, part II: color test and TLC. Yakugaku Zasshi 128:981–987

    PubMed  Article  CAS  Google Scholar 

  4. 4.

    Uchiyama N, Kikura-Hanajiri R, Kawahara N, Goda Y (2008). Analysis of designer drugs detected in the products purchased in fiscal year 2006. Yakugaku Zasshi 128:1499–1505

    PubMed  Article  CAS  Google Scholar 

  5. 5.

    Min JZ, Shimizu Y, Toyoóka T, Inagaki S, Kikura-Hanajiri R, Goda Y (2008). Simultaneous determination of 11 designated hallucinogenic phenethylamines by ultra-fast liquid chromatography with fluorescence detection. J Chromatogr B 873:187–194

    Article  CAS  Google Scholar 

  6. 6.

    Maruyama T, Kamakura H, Kikura-Hanajiri R, Goda Y (2008). Authentication and ultra performance liquid chromatography (UPLC)/MS analysis of magic mint, Salvia divinorum and its related plants. Yakugaku Zasshi 128:179–183

    PubMed  Article  CAS  Google Scholar 

  7. 7.

    Kawamura M, Kikura-Hanajiri R, Goda Y (2008). Survey of current trends in the abuse of psychotropic plants using LCMS. Jpn J Food Chem 15:73–78

    CAS  Google Scholar 

  8. 8.

    Takayama H, Aimi N, Sakai S (2000). Chemical studies on the analgesic indole alkaloids from the traditional medicine (Mitragyna speciosa) used for opium substitute. Yakugaku Zasshi 120:959–967

    PubMed  CAS  Google Scholar 

  9. 9.

    Takayama H (2004). Chemistry and pharmacology of analgesic indole alkaloids from the rubiaceous plant, Mitragyna speciosa. Chem Pharm Bull 52:916–928

    PubMed  Article  CAS  Google Scholar 

  10. 10.

    Ponglux D, Wongseripipatana S, Takayama H, Kikuchi M, Kurihara M, Kitajima M, Aimi N, Sakai S (1994). A new indole alkaloid, 7 alpha-hydroxy-7H-mitragynine, from Mitragyna speciosa in Thailand. Planta Med 60:580–581

    PubMed  Article  CAS  Google Scholar 

  11. 11.

    Matsumoto K, Mizowaki M, Suchitra T, Takayama H, Sakai S, Aimi N, Watanabe H (1996). Antinociceptive action of mitragynine in mice: evidence for the involvement of supraspinal opioid receptors. Life Sci 59:1149–1155

    PubMed  Article  CAS  Google Scholar 

  12. 12.

    Thongpradichote S, Matsumoto K, Tohda M, Takayama H, Aimi N, Sakai S, Watanabe H (1998). Identification of opioid receptor subtypes in antinociceptive actions of supraspinally administered mitragynine in mice. Life Sci 62:1371–1378

    PubMed  Article  CAS  Google Scholar 

  13. 13.

    Matsumoto K, Horie S, Ishikawa H, Takayama H, Aimi N, Ponglux D, Watanabe K (2004). Antinociceptive effect of 7-hydroxymitragynine in mice: discovery of an orally active opioid analgesic from the Thai medicinal herb Mitragyna speciosa. Life Sci 74:2143–2155

    PubMed  Article  CAS  Google Scholar 

  14. 14.

    Horie S, Koyama F, Takayama H, Ishikawa H, Aimi N, Ponglux D, Matsumoto K, Murayama T (2005). Indole alkaloids of a Thai medicinal herb, Mitragyna speciosa, that has opioid agonistic effect in guinea-pig ileum. Planta Med 71:231–236

    PubMed  Article  CAS  Google Scholar 

  15. 15.

    Matsumoto K, Horie S, Takayama H, Ishikawa H, Aimi N, Ponglux D, Murayama T, Watanabe K (2005). Antinociception, tolerance and withdrawal symptoms induced by 7-hydroxymitragynine, an alkaloid from the Thai medicinal herb Mitragyna speciosa. Life Sci 78:2–7

    PubMed  Article  CAS  Google Scholar 

  16. 16.

    Matsumoto K, Hatori Y, Murayama T, Tashima K, Wongseripipatana S, Misawa K, Kitajima M, Takayama H, Horie S (2006). Involvement of mu-opioid receptors in antinociception and inhibition of gastrointestinal transit induced by 7-hydroxymitragynine, isolated from Thai herbal medicine Mitragyna speciosa. Eur J Pharmacol 549:63–70

    PubMed  Article  CAS  Google Scholar 

  17. 17.

    Maruyama T, Kawamura M, Kikura-Hanajiri R, Takayama H, Goda Y (2009). The botanical origin of Kratom (Mitragyna speciosa; Rubiaceae) available as abused drugs in the Japanese markets. J Nat Med. doi:10.1007/s11418-009-0325-9

  18. 18.

    Kitajima M, Nakayama T, Kogure N, Wongseripipatana S, Takayama H (2007). New heteroyohimbine-type oxindole alkaloid from the leaves of Thai Mitragyna hirsute. J Nat Med 61:192–195

    Article  CAS  Google Scholar 

Download references

Author information

Affiliations

Authors

Corresponding author

Correspondence to Ruri Kikura-Hanajiri.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Kikura-Hanajiri, R., Kawamura, M., Maruyama, T. et al. Simultaneous analysis of mitragynine, 7-hydroxymitragynine, and other alkaloids in the psychotropic plant “kratom” (Mitragyna speciosa) by LC-ESI-MS. Forensic Toxicol 27, 67–74 (2009). https://doi.org/10.1007/s11419-009-0070-5

Download citation

Keywords

  • Mitragynine
  • 7-Hydroxymitragynine
  • Mitragyna speciosa
  • Kratom
  • Opioid agonist
  • LC-MS