Quantitative Analysis of the Marker Constituents in Yongdamsagan-Tang using Liquid Chromatography-Electrospray Ionization-Tandem Mass Spectrometry

LC-ESI-MS/MS를 이용한 용담사간탕의 주요 성분 분석

  • Seo, Chang-Seob (K-herb Research Center, Korea Institute of Oriental Medicine) ;
  • Ha, Hyekyung (K-herb Research Center, Korea Institute of Oriental Medicine)
  • 서창섭 (한국한의학연구원 K-herb연구단) ;
  • 하혜경 (한국한의학연구원 K-herb연구단)
  • Received : 2017.10.27
  • Accepted : 2017.12.01
  • Published : 2017.12.29

Abstract

Yongdamsagan-tang has been used to treat the urinary disorders, acute- and chronic-urethritis, and cystitis in Korea. In this study, an ultra-performance liquid chromatography-electrospray ionization-mass spectrometry (UPLC-ESI-MS/MS) method was established for simultaneous analysis of the 20 bioactive marker compounds, geniposidic acid, chlorogenic acid, geniposide, liquiritin apioside, acteoside, calceolarioside B, liquiritin, nodakenin, baicalin, liquiritigenin, wogonoside, baicalein, glycyrrhizin, wogonin, glycyrrhizin, wogonin, saikosaponin A, decursin, decursinol angelate, alisol B, alisol B acetate, and pachymic acid in traditional herbal formula, Yongdamsagan-tang. Chromatographic separations of all marker compounds were conducted using a Waters Acquity UPLC BEH $C_{18}$ analytical column ($2.1{\times}100mm$, $1.7{\mu}m$) at $45^{\circ}C$ using a mobile phase of 0.1% (v/v) formic acid in water and acetonitrile with gradient elution. The MS analysis was performed using a Waters ACQUITY TQD LC-MS/MS coupled with an electrospray ionization source in the positive and negative modes. The flow rate was 0.3 mL/min and injection volume was $2.0{\mu}L$. The correlation coefficient of 20 marker compounds in the test ranges was 0.9943-1.0000. The limits of detection and quantification values of the all marker components were 0.11-6.66 and 0.34-19.99 ng/mL, respectively. As a result of the analysis using the optimized LC-ESI-MS/MS method, three compounds, geniposidic acid (from Plantaginis Semen), alisol B (from Alismatis Rhizoma), and pachymic acid (from Poria Sclerotium), were not detected in this sample. While the amounts of the 17 compounds except for the geniposidic acid, alisol B, and pachymic acid were $0.04-548.13{\mu}g/g$ in Yongdamsagan-tang sample. Among these compounds, baicalin, bioactive marker compound of Scutellariae Radix, was detected at the highest amount as a $548.13{\mu}g/g$.

Keywords

References

  1. Lee, I. J., Lee, D. N., Seo, I. B. and Kim, H. J. (2011) Effects of Yongdamsagan-tang on the progression of the estradiol valerate-induced polycystic ovaries and on the conception in rats. J. Orient. Obstet. Gynecol. 24: 48-72.
  2. Heo, J. (2004) Donguibogam, 313. Namsandang, Seoul.
  3. Yun, H. J., Kim, H. S., Heo, S. K., Hwang, S. G., Park, W. H. and Park, S. D. (2007) Effect of Yong-dan-sa-gan-tang on apoptosis in human hepatoma HepG2. Korean J. Orient. Med. Prescr. 15: 127-137.
  4. Qi, F., Wang, Z., Cai, P., Zhao, L., Gao, J., Kokudo, N., Li, A., Han, J. and Tang, W. (2013) Traditional Chinese medicine and related active compounds: A review of their role on hepatitis B virus infection. Drug Discov. Ther. 7: 212-224.
  5. Jung, M. Y., Kin, D. S., Kim, M. J., Song, J. S., Park, S. Y., Kim, J. H. and Choi, J. H. (2008) Three cases of herpes zoster improved by Yongdamsagantang. J. Korean Orient. Med. Ophthalmol. Otolaryngol. Dermatol. 21: 176-183.
  6. Koo, C. M., Park, Y. J., Park, J. H., Heo, G. J., Nam, C. G. and Sun, J. K. (2003) A case report of herpes zoster with acute pain by Yongdamsagan-tang (longdanxiegan-tang). Korean J. Orient. Int. Med. 24: 151-156.
  7. Kang, D. H., Kim, Y. D., Kim, C. N. and Min, J. Y. (2003) The effect of Youndamsagan-tang on a case of septic knee: A case report. Korean J. Physiol. Pathol. 17: 1547-1551.
  8. He, Y. M., Zhu, S., Ge, Y. W., Kazuma, K., Zou, K., Cai, S. Q. and Komatsu, K. (2015) The anti-inflammatory secoiridoid glycosides from Gentianae Scabrae Radix: the root and rhizome of Gentiana scabra. J. Nat. Med. 69: 303-312. https://doi.org/10.1007/s11418-015-0894-8
  9. Han, D. S. and Lee. D. K. (1985) Separation and determination of saikosaponins in Bupleuri Radix with HPLC. Kor. J. Pharmacogn. 16: 175-179.
  10. Lee, J. H., Kwon, O. S., Jin, H. G., Woo, E. R., Kim, Y. S. and Kim, H. P. (2012) The rhizomes of Alisma orientale and alisol derivatives inhibit allergic response and experimental atopic dermatitis. Biol. Pharm. Bull. 35: 1581-1587. https://doi.org/10.1248/bpb.b110689
  11. Gao, H. M., Wang, Z. M., Qu, L., Fu, X. T. and Li, L. (2007) Determination of calceolarioside B in Caulis Akebiae by RPHPLC. Zhongguo Zhong Tao Za Zhi 32: 476-478.
  12. Sung, Y. Y., Kim, D. S. and Kim, H. K. (2015) Akebia quinata extract exerts anti-obesity and hypolipidemic effects in high-fat diet-fed mice and 3T3-L1 daipocytes. J. Ethnopharmacol. 168: 17-24. https://doi.org/10.1016/j.jep.2015.03.051
  13. Oh, J. S., Lee, J. G., Jung, H. W., Choi, J. Y., Choi, E. H., Kim, D. C., Kim, J. A., Son, J. K. and Lee, S. H. (2007) Isolation of melanin biosynthesis inhibitory compounds from the seeds of Plantago asiatica L. Kor. J. Pharmacogn. 38: 376-381.
  14. Kim, B. H., Park, K. s. and Chang, L. M. (2009) Elucidation of anti-inflammatory potencies of Eucommia ulmoides bark and Plantago asiatica seeds. J. Med. Food 12: 764-769. https://doi.org/10.1089/jmf.2008.1239
  15. Li, G., Xu, M. L., Lee, C. S., Woo, M. H., Chang, H. W. and Son, J. K. (2004) Cytotoxicity and DNA topoisomerases inhibitory of constituents from the sclerotium of Poria cocos. Arch. Pharm. Res. 27: 829-833. https://doi.org/10.1007/BF02980174
  16. Kim, N. J., Jung, E. A., Kim, H. J., Sim, S. B. and Kim, J. W. (2000) Quality evaluation of various dried roots of Rehmannia glutinosa. Kor. J. Pharmacogn. 31: 130-141.
  17. Ahn, M. J., Lee, M. K., Kim, Y. C. and Sung, S. H. (2008) The simultaneous determination of coumarins in Angelica gigas root by high performance liquid chromatography-diode array detector coupled with electrospray ionization/mass spectrometry. J. Pharm. Biomed. Anal. 46: 258-266. https://doi.org/10.1016/j.jpba.2007.09.020
  18. Lee, E. J., Hong, J. K. and Whang, W. K. (2014) Simultaneous determination of bioactive marker compounds from Gardeniae Fructus by high performance liquid chromatography. Arch. Pharm. Res. 37: 992-1000. https://doi.org/10.1007/s12272-013-0293-1
  19. Tong, L., Wan, M., Zhang, L., Zhu, Y., Sun, H. and Bi, K. (2012) Simultaneous determination of baicalin, wogonoside, baicalein, wogonin, oroxylin A and chrysin of Radix Scutellariae extract in rat plasma by liquid chromatography tandem mass spectrometry. J. Pharm. Biomed. Anal. 70: 6-12. https://doi.org/10.1016/j.jpba.2012.03.051
  20. Zhang, Q. and Ye, M. (2009) Chemical analysis of the Chinese herbal medicine Gan-Cao (licorice). J. Chromatogr. A. 1216: 1954-1969. https://doi.org/10.1016/j.chroma.2008.07.072
  21. Lee, K. H. (2013) The dispensatory on the visual and organoleptic examination of herbal medicine, 24-723. National Institute of Food and Drug Safety Evaluation, Seoul.
  22. Peng, M., Zhang, Y., Shi, S. and Peng, S. (2013) Simultaneous ligand fishing and identification of human serum albumin binders from Eucommia ulmoides bark using surface plasmon resonance-high performance liquid chromatography-tandem mass spectrometry. J. Chromatogr. B 940: 86-93. https://doi.org/10.1016/j.jchromb.2013.09.032
  23. Jaiswal, R., Muller, H., Muller, A., Karar, M. G. E. and Kuhnert, N. (2014) Identification and characterization of chlorogenic acid, chlorogenic acid glycosides and flavonoids from Lonicera henryi L. (Caprifoliaceae) leaves by $LC-MS^{n}$. Phytochemistry 108: 252-263. https://doi.org/10.1016/j.phytochem.2014.08.023
  24. Zhou, T., Liu, H., Wen, J., Fan, G., Chai, Y. and Wu, Y. (2010) Fragmentation study of iridoid glycosides including epimers by liquid chromatography-diode array detection/electrospray ionization mass spectrometry and its application in metabolic fingerprint analysis of Gardenia jasminoides Ellis. Rapid Commun. Mass Spectrom. 24: 2520-2528. https://doi.org/10.1002/rcm.4643
  25. Li, L., Liang, S., Du, F. and Li, C. (2007) Simultaneous quantification of multiple licorice flavonoids in rat plasma. J. Am. Soc. Mass Spectrom. 18: 778-782. https://doi.org/10.1016/j.jasms.2006.12.011
  26. Li, Y., Gan, L., Li, G. Q., Deng, L., Zhang, X. and Deng, Y. (2014) Pharmacokinetics of plantamajoside and acteoside from Plantago asiatica in rats by liquid chromatography-mass spectrometry. J. Pharm. Biomed. Anal. 89: 251-256. https://doi.org/10.1016/j.jpba.2013.11.014
  27. Tan, G., Zhu, Z., Jing, J., Lv, L., Lou, Z., Zhang, G. and Chai, Y. (2011) Characterization of constituents in Sini decoction and rat plasma by high-performance liquid chromatography with diode array detection coupled to time-of-flight mass spectrometry. Biomed. Chromagogr. 25: 913-924. https://doi.org/10.1002/bmc.1544
  28. Kim, M. K., Yang, D. H., Jung, M., Jung, E. H., Eom, H. Y., Suh, J. H., Min, J. W., Kim, U., Min, H., Kim, J. and Han, S. B. (2011) Simultaneous determination of chromones and coumarins in Radix Saposhnikoviae by high performance liquid chromatography with diode array and tandem mass detectors. J. Chromatogr. A. 1218: 6319-6330. https://doi.org/10.1016/j.chroma.2011.06.103
  29. Xu, L., Song, R., Tian, J. X., Tian, Y., Liu, G. Q. and Zhang, Z. J. (2012) Analysis of saikosaponins in rat plasma by anionic adducts-based liquid chromatography tandem mass spectrometry method. Biomed. Chromatogr. 26: 808-815. https://doi.org/10.1002/bmc.1734
  30. Tong, L., Wan, M., Zhang, L., Zhu, Y., Sun, H. and Bi, K. (2012) Simultaneous determination of baicalin, wogonoside, baicalein, wogonin, oroxylin A and chrysin of Radix Scutellariae extract in rat plasma by liquid chromatography tandem mass spectrometry. J. Pharm. Biomed. Anal. 70: 6-12. https://doi.org/10.1016/j.jpba.2012.03.051
  31. Zhao, J., Su, C., Yang, C., Liu, M., Tang, L., Su, W. and Liu, Z. (2012) Determination of ginsenosides Rb1, Rb2, and Rb3 in rat plasma by a rapid and sensitive liquid chromatography tandem mass spectrometry method: Application in a pharmacokinetic study. J. Pharm. Biomed. Anal. 64-65: 94-97. https://doi.org/10.1016/j.jpba.2012.02.017
  32. Wang, Y., Yang, L., He, Y. Q., Wang, C. H., Welbeck, E. W., Bligh, S. W. and Wang, Z. T. (2008) Characterization of fiftyone flavonoids in a Chinese herbal prescription Longdan Xiegan Decoction by high-performance liquid chromatography coupled to electrospray ionization tandem mass spectrometry and photodiode array detection. Rapid Commun. Mass Spectrom. 22: 1767-1778. https://doi.org/10.1002/rcm.3536
  33. Ahn, M. J., Lee, M. K., Kim, Y. C. and Sung, S. H. (2008) The simultaneous determination of Coumarin in Angelica gigas root by high performance liquid chromatography-diode array detector coupled with electrospray ionization/mass spectrometry. J. Pharm. Biomed. Anal. 46: 258-266. https://doi.org/10.1016/j.jpba.2007.09.020
  34. Chen, L., Qi, J., Chang, Y., Zhu, D. and Yu, B. (2009) Identification and determination of the major constituents in traditional Chinese medicinal formula Danggui-Shaoyao-San by HPLC-DAD-ESI-MS/MS. J. Pharm. Biomed. Anal. 50: 127-137. https://doi.org/10.1016/j.jpba.2009.03.039