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HPLC analysis of ammonium glycyrrhizate listed in the European, United States, and Japanese Pharmacopoeias under reported and modified conditions: revision of the peak assignment for 18α-glycyrrhizin in the European and United States Pharmacopoeias

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Abstract

We examined ammonium glycyrrhizate listed in the monographs of the European Pharmacopoeia (EP) and United States Pharmacopoeia (USP) as well as in the reagents and solutions used in the general test of the Japanese Pharmacopoeia by performing HPLC on their sample standards or reference reagents under reported and modified conditions. Comparative experiments involving five authentic samples, namely, 18β-glycyrrhizin (1), 18α-glycyrrhizin (2), licorice–saponin G2 (3), licorice–saponin H2 (4), and galacturonic acid-replaced glycyrrhizin (the 4″-epimer of 18β-glycyrrhizin) (5), led us to propose the revision of the peak assignment of 18α-glycyrrhizin (2) and postscript a possible co-existence of galacturonic acid-replaced glycyrrhizin (5) as a hidden component in the EP and USP. We also proposed that the α-configuration used in the nomenclature of the glycosidic bond between aglycone and the sugar units of ammonium glycyrrhizate and impurities in the EP and USP should be revised to the β-configuration.

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References

  1. Hosseinzadeh H, Nassiri-Asl M (2015) Pharmacological effects of Glycyrrhiza spp. and its bioactive constituents: update and review. Phytother Res 29:1868–1886

    Article  Google Scholar 

  2. Kao T-C, Wu C-H, Yen G-C (2014) Bioactivity and potential health benefits of licorice. J Agric Food Chem 62:542–553

    Article  CAS  Google Scholar 

  3. Tolstikovy GA, Baltina LA et al (1997) Glycyrrhizic acid. Russ J Bioorg Chem 23:625–642

    Google Scholar 

  4. Ito Y, Ishizaki K, Sugimoto N, Tada A, Akiyama T, Sato K, Akiyama H, Goda Y (2015) Confirmation of the configuration of two glucuronic acid units in glycyrrhizic acid. Jpn J Food Chem Safety 22:32–37

    CAS  Google Scholar 

  5. Miyashita A, Kuramoto T, Okada K (1981) 18α-Glycyrrhizinic acid. UK Patent GB 2071665 A

  6. Baltina LA Jr, Stolyarova OV, Baltina LA, Kondratenko RM, Plyasunova OA, Pokrovskii AG (2010) Synthesis and antiviral activity of 18α-glycyrrhizic acid and its esters. Pharm Chem J 44:299–302

    Article  CAS  Google Scholar 

  7. Jitrangsri K, Kamata K, Akiba M, Yajiri Y, Ishibashi M, Tatsuzaki J, Ishikawa T (2022) Is 18α-glycyrrhizin a real natural product? Improved preparation of 18α-glycyrrhizin from 18β-glycyrrhizin as a positive standard for HPLC analysis of licorice extracts. J Nat Med 76:376–378

    Article  Google Scholar 

  8. “Ammonium glycyrrhizate” in European Pharmacopoeia-10th ed (2019) Vol II Monographs A 01/2017:1772, p 1833–1834

  9. “Ammonium glycyrrhizinate” in British Pharmacopoeia (2021) Vol II-166

  10. “Ammonium glycyrrhizate” in United States Pharmacopoeia-US42/NF37 (2019) NF Monographs: p 5573–5574

  11. Kitagawa I, Hori K, Sakagami M, Zhou J-L, Yoshikawa M (1993) Saponin and sapogenol. XLVIII. On the constituents of the roots of Glycyrrhiza uralensis Fischer from northern China (2). Licorice-saponin D3, E2, F3, G2, H2, J2, and K2. Chem Pharm Bull 41:1337–1345

    Article  CAS  Google Scholar 

  12. Vora PS (1982) High pressure liquid chromatographic determination of glycyrrhizic acid or glycyrrhizic acid salts in various licorice products: collaborative study. J Assoc Off Anal Chem 65:572–574

    CAS  Google Scholar 

  13. Spinks EA, Fenwick GR (1990) The determination of glycyrrhizin in selected UK liquorice products. Food Add Contam 7:769–778

    Article  CAS  Google Scholar 

  14. Koga K, Ohmachi K, Kawashima S, Takeda K, Murakami M (2000) Determination of 18α-glycyrrhizin and 18β-glycyrrhizin in dog plasma by high-performance liquid chromatography. J Chromatogr B 738:165–158

    Article  CAS  Google Scholar 

  15. “Monoammonium glycyrrhizinate for resolution check” in The Japanese Pharmacopoeia 18th ed (JP XVIII) (2021) p 328

  16. Uchida M, Wada M, Nakamura H, Ishihara S, Mano N, Komoda Y (1988) Isolation of triterpene glycoside and sweeteners containings it. Japanese Patent JP63267795A

  17. Masada S, Yamaji H, Takeda O, Shimada Y, Komatsu K, Uchiyama N, Hakamatsuka T (2017) 新疆甘草に含まれるグリチルリチン酸及びガラクツログリチルリチン酸量の調査. Nihon Shouyaku Gakkai, 64th annual meeting 1P–76: 199

  18. Goda Y (2017) Studies for quality control of pharmaceuticals focusing on revision of monographs. The Japanese Pharmacopoeia. Research on Regulatory Science of Pharmaceutical and Medical Devices

  19. Kanai K, Hori C, Daikonya A, Harai K, Ou B, Okonogi A, Yokoya Y (2018) Study on shortening of analysis time in high performance liquid chromatography X -Study on quantification of glycyrrhizic acid in JP17 Glycyrrhiza and Powdered Glycyrrhiza. Res Home Med No 37:33–41

    Google Scholar 

  20. Koseki Y (2018) Manufacturing method of glycyrrhizic acid and galacturonic acid glycyrrhizic acid and intermediates used in the method. Japanese Patent P2018104352A

  21. The Pharmaceutical and Medical Device Regulatory Science Society of Japan (ed) (2021) The Japanese Pharmacopoeia 18th ed. In: Technical Information (JPTI 2021). Jiho Inc., Tokyo, pp 1277–1281

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Correspondence to Tsutomu Ishikawa or Nahoko Uchiyama.

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Kamata, K., Tatsuzaki, J., Ishikawa, T. et al. HPLC analysis of ammonium glycyrrhizate listed in the European, United States, and Japanese Pharmacopoeias under reported and modified conditions: revision of the peak assignment for 18α-glycyrrhizin in the European and United States Pharmacopoeias. J Nat Med 77, 202–206 (2023). https://doi.org/10.1007/s11418-022-01649-8

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