SIMULTANEOUS QUALITATIVE AND QUANTITATIVE ANALYSIS OF CERTAIN FLAVONOID GLYCOSIDES AND TERPENE LACTONES IN PHARMACEUTICAL PRODUCTS CONTAINING GINKGO BILOBA L. LEAF EXTRACT BY LC-TOF/MS
Year 2023,
Issue: 053, 41 - 58, 30.06.2023
Selda Doğan
,
Hatice Fidan
,
Nefise Şahin
Abstract
In this study, three drugs and three dietary supplements containing G. biloba leaf extract were obtained from pharmacies and two dietary supplements were obtained from herbalists. Certain flavonoid glycosides and ginkgolide A, B, C, and J amounts of these products were determined simultaneously using LC-TOF/MS. The total phenol and flavonoid content of these products were also determined with spectrophotometric technique.
Objective: We aimed to emphasize that adulteration is still a critical problem in herbal products frequently used during the Covid-19 pandemic and propose a fast, validated analytical method for detecting adulteration.
Conclusions: The qualitative and quantitative results of all drugs and dietary supplements obtained from the pharmacy were compatible with the information declared by the manufacturer. However, neither qualitative nor quantitative flavonoid glycosides or ginkgolides A, B, and C were detected, although the total phenolic and flavonoid values were very high in one of the dietary supplements taken by the herbalist. The study's data is considered significant, mainly due to the considerable increase in interest in herbal products during the Covid-19 pandemic
Supporting Institution
This study was funded by the Mersin University Scientific Research Project Unit with the project no. 2021-1-TP2-4135.
Project Number
2021-1-TP2-4135
References
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- [22] Hasler, A., and Sticher, O. (1992). Identification and determination of flavonoids from Ginkgo biloba by high performance liquid chromatography. Journal of Chromatography A, 605(1), 41–48.
- [23] Liu, X.G., Yang, H., Cheng, X.L., Liu, L., Qin, Y., Wang, Q., Qi, L.W., and Li, P. (2014). Direct analysis of 18 flavonol glycosides, aglycones and terpene trilactones in Ginkgo biloba tablets by matrix solid phase dispersion coupled with ultra-high performance liquid chromatography tandem triple quadrupole mass spectrometry. Journal of Pharmaceutical and Biomedical Analysis, (97),123–128.
- [24] Lin, L.Z., Chen, P., Ozcan, M., and Harnly, J.M. (2008). Chromatographic profiles and identification of new phenolic components of Ginkgo biloba leaves and selected products. Journal of agricultural and food chemistry, 56(15), 6671–6679.
- [25] Van Beek, T.A., and Montoro, P. (2009). Chemical analysis and quality control of Ginkgo biloba leaves, extracts, and phytopharmaceuticals. Journal of Chromatography A, 1216(11), 2002–2032.
- [26] Rimmer, C.A., Howerton, S.B., Sharpless, K.E., Sander, L.C., Long, S.E., Murphy, K.E., Porter, B.J., Putzbach, K., Rearick, M.S., Wise, S.A., Wood, L.J., Zeisler, R., Hancock, D.K., Yen, J.H., Betz, J.M., Nguyenpho, A., Yang, L., Scriver, C., Willie, S., Sturgeon, R., Schaneberg, B., Nelson, C., Skamarack, J., Pan, M., Levanseler, K., Gray, D., Waysek, E.H., Blatter, A., and Reich, E. (2007). Characterization of a suite of ginkgo-containing standard reference materials. Analytical and Bioanalaytical Chemistry, 389(1), 179–96.
- [27] Chandra, A., Li, Y., Rana, J., Persons, K., Hyun, C., Shen, S., and Mulder, T. (2011). Qualitative categorization of supplement grade Ginkgo biloba leaf extracts for authenticity. Journal of Functional Foods, 3(2), 107–114.
- [28] Li,W., and Fitzloff, J.F. (2002). HPLC determination of flavonoids and terpene lactones ın commercıal Gınkgo bıloba products. Journal of Liquid Chromatography & Related Technologies, 25(16), 2501–2514.
- [29] Hasler, A., Sticher, O., and Meier, B. (1992). Identification and determination of the flavonoids from Ginkgo biloba by high-performance liquid chromatography. Journal of Chromatography A, 605(1), 41–48.
- [30] Kressmann, S., Muller, W.E., and Blume, H.H. (2002). Pharmaceutical quality of different Ginkgo biloba brands. Journal of Pharmacy and Pharmacology, 54(5), 661–669.
- [31] Booker, A., Frommenwiler, D., Reich, E., Horsfield, S., and Heinrich, M. (2016). Adulteration and poor quality of Ginkgo biloba supplements. Journal of Herbal Medicine, 6(2), 79–87.
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- [33] Liu, X.G., Wu, S.Q., Li, P., and Yang, H. (2015). Advancement in the chemical analysis and quality control of flavonoid in Ginkgo biloba. Journal of Pharmaceutical and Biomedical Analysis, 113, 212–225.
- [34] Wohlmuth, H., Savage, K., Dowell, A., and Mouatt, P. (2014). Adulteration of Ginkgo biloba products and a simple method to improve its detection. Phytomedicine, 21(6), 912–918.
- [35] López-Gutiérrez, N., Romero-González, R., Vidal, J.L.M., and Frenich, A.G. (2016). Quality control evaluation of nutraceutical products from Ginkgo biloba using liquid chromatography coupled to high resolution mass spectrometry. Journal of Pharmaceutical and Biomedical Analysis, 121, 151–160.
- [36] Tokalıoglu, S. (2012). Determination of trace elements in commonly consumed medicinal herbs by ICP-MS and multivariate analysis. Food Chemistry, 134(4), 2504–2508.
- [37] Zhao, L.J., Liu, W., Xiong, S.H., Tang, J., Lou, Z.H., Xie, M.X., Xia, B.H., Lin, L.M., and Liao, D.F. (2018). Determination of total flavonoids contents and antioxidant activity of Ginkgo biloba leaf by near-infrared reflectance method. International Journal of Analytical Chemistry, 2018, 1–7.
- [38] Li, C.Y., Lin, C.H., Wu, C.C., Lee, K.H., and Wu, T.S. (2004). Efficient 1H nuclear magnetic resonance method for improved quality control analyses of Ginkgo constituents. Journal of Agricultural and Food Chemistry, 52(12), 3721–3725.
- [39] Al‐kuraishy, H.M., Al‐Gareeb, A.I., Kaushik, A., Kujawska, M., and Batiha, G.E.S. (2022). Ginkgo biloba in the management of the COVID‐19 severity. Archiv der Pharmazie, 355, 2200188.
- [40] Czigle, S., Tóth, J., Jedlinszki, N., Radnai, E.H., Csupor, D., and Tekelová, D. (2018). Ginkgo biloba food supplements on the European Market –adulteration patterns revealed by quality control of selected samples. Planta Medica, 84, 475–482.
- [41] Slinkard, K., and Singleton, V.L. (1977). Total phenols analysis: Automation and comparison with manual methods. American Journal of Enology and Viticulture, 28, 49 – 55.
- [42] Kim, D.O., Jeong, S.W., and Lee, C.Y. (2003). Antioxidant capacity of phenolic phytochemicals from various cultivars of plums. Food Chemistry, 81(3), 321 – 326.
- [43] Park, Y.G., Kim, S.J., Jung, H.Y., Kang, Y.M., Kang, S.M., Prasad, D.T., Kim, S.W., and Choi, M.S. (2004). Variation of ginkgolides and bilobalide contents in leaves and cell cultures of Ginkgo biloba L. Biotechnology and Bioprocess Engineering, 9, 35-40.
- [44] Mesbah, M.K., Khalifa, S.I., Gindy, A.E., and Tawfik, KA. (2005). HPLC determination of certain flavonoids and terpene lactones in selected Ginkgo biloba L. Phytopharmaceuticals. Farmaco, 60(6-7),583-590.
- [45] Van Beek, T.A. (2005). Ginkgolides and bilobalide: their physical, chromatographic and spectroscopic properties. Bioorganic and Medicinal Chemistry, 13(17), 5001-5012.
- [46] Sevindik, O., Guclu, G., Agirman, B., Selli, S., Kadiroglu, P., Bordiga, M., Capanoglu, E., and Kelebek, H. (2022). Impacts of selected lactic acid bacteria strains on the aroma and bioactive compositions of fermented gilaburu (Viburnum opulus) juices. Food Chemistry, 378, 132079.
- [47] Fransen, H.P., Pelgrom, S.M.G.J., Stewart-Knox, B., de Kaste, D., and Verhagen, H. (2010). Assessment of health claims, content, and safety of herbal supplements containing Ginkgo biloba. Food and Nutrition Research, 54, 5221.
- [48] Chen, P., Ozcan, M., and Harnly, J. (2007). Chromatographic fingerprint analysis for evaluation of Ginkgo biloba products. Analytical and Bioanalytical Chemistry, 389(1), 251–61.
- [49] Demirezer, L.Ö., Büyükkaya, A., Uçaktürk, E, Uz, A.K., Güvenalp, Z., and Palaska, E. (2014). Adulteration determining of pharmaceutical forms of Ginkgo biloba extracts from different international manufacturers. Records of Natural Products, 8, 4, 394-400.
- [50] Dubber, M.J., and Kanfer, I. (2004). High-performance liquid chromatographic determination of selected flavonols in Ginkgo biloba solid oral dosage forms. Journal of Pharmaceutical Sciences, 24, 7(3), 303-309.
Year 2023,
Issue: 053, 41 - 58, 30.06.2023
Selda Doğan
,
Hatice Fidan
,
Nefise Şahin
Project Number
2021-1-TP2-4135
References
- [1] Mohanta, T.K., Occhipinti, A., Zebelo, S.A., Foti, M., Fliegmann, J., Bossi, S., Maffei, M.E., and Bertea, C.N. (2012). Ginkgo biloba responds to herbivory by activating early signaling and direct defenses. Plos One, 7(3), 1-14.
- [2] Lin, H.Y., Li, W.H., Lin, C.F., Wu, H.R., and Zhao, Y.P. (2022). International biological flora: Ginkgo biloba. Journal of Ecology, 110(4), 951-982.
- [3] Singh, B., Kaur, P., Gopichand, S.R.D., and Ahuja, P.S. (2008). Biology and chemistry of Ginkgo biloba. Fitoterapia, 79(6), 401–418.
- [4] Belwal, T., Giri, L., Bahukhandi, A., Tariq, M., Kewlani, P., Bhatt, I.D., and Rawl, R.S. (2019). Ginkgo Biloba. Nonvitamin and Nonmineral Nutritional Supplements, 241-250.
- [5] Tronnier, H. (1968). Clinical-pharmacological studies on the effect of an extract from Ginkgo biloba L. in the postthrombotic syndrome. Arzneimittelforschung, 18 (5), 551–554.
- [6] Mussgnug, G., and Alemany, J. (1968). Studies on peripheral arterial blood circulation disorders. XV. On the problems of conservative therapy of obliterating peripheral blood circulation disorders demonstrated on tincture and extract from Ginkgo biloba L. Arzneimittelforschung, 18 (5), 543–550.
- [7] Montanini, R., and Gaspari, G. (1969). Use of an extract of Ginkgo biloba (Tebonin) in the therapy of cerebral vascular diseases. Minerva Cardioangiologica, 17 (12), 1096–1102.
- [8] Locatelli, G.R., and Sorbini, E. (1969). Effects of Tebonin (extract from leaves of Ginkgo biloba L.) in the treatment of senile peripheral arteriopathies. Minerva Cardioangiologica, 17 (12), 1103–1108.
- [9] Kramer, F., and Ortigoza, A. (2018). Ginkgo biloba for the treatment of tinnitus. Medwave, 18 (26), 7295.
- [10] Yang, G., Wang, Y., Sun, J., Zhang, K., and Liu, J. (2016). Ginkgo biloba for mild cognitive impairment and Alzheimer’s disease: a systematic review and meta-analysis of randomized controlled trials. Current Topics in Medicinal Chemistry, 16(5), 520–528.
- [11] Solis, M.I., Acero, N., Morell, F.B., Castillo, E., Rosende, M.E.G., Mingarro, D.M., Ortega, T., Sanahuja, M.A., and Villagrasa, V. (2019). Neuroprotective potential of Ginkgo biloba in retinal diseases. Planta Medica, 85 (17), 1292–1303.
- [12] Rodriguez, M., Ringstad, L., Schäefer, P., Just, S., Hofer, H.W., Malmsten, M., and Siegel, G. (2007). Reduction of atherosclerotic nanoplaque formation and size by Ginkgo biloba (EGb 761) in cardiovascular high-risk patients. Atherosclerosis, 192 (2), 438–444.
- [13] Oskouei, D.S., Rikhtegar, R., Hashemilar, M., Bazargani, H.S., Bonab, M.S., Hokmabadi, E.S., Zarrintan, S., and Sharifipour, E. (2013). The effect of Ginkgo biloba on functional outcome of patients with acute ischemic stroke:a double-blind, placebo-controlled, randomized clinical trial. Journal of Stroke Cerebrovascular Diseases, 22(8), 557-563.
- [14] Muir, A.H., Robb, R., McLaren, M., Daly, F., and Belch, J.J.F. (2002). The use of Ginkgo biloba in Raynaud’s disease: a double-blind placebo-controlled trial. Vascular Medicine, 7(4) 265–267.
- [15] Zhu, H.W., Shi, Z.F., and Chen, Y.Y. (2005). Effect of extract of Ginkgo biloba leaf on early diabetic nephropathy. Zhongguo Zhong Xi Yi Jie He Za Zhi, 25 (10), 889–910.
- [16] Van Beek, T.A. (2002). Chemical analysis of Ginkgo biloba leaves and extracts. Journal Chromatography A, 967(1), 21–55.
- [17] Tabassum, N.E., Das, R., Lami, M.S., Chakraborty, A.J., Mitra, S., Tallei, T.E., Idroes, R., Mohamed, A.A.R., Hossain, M.J., Dhama, K., Hedeab, G.M., and Emran, T.B. (2022). Ginkgo biloba: A treasure of functional phytochemicals with multimedicinal applications. Evidence-Based Complementary and Alternative Medicine, 2022,1-30.
- [18] Mahadevan, S., and Park, Y. (2008). Multifaceted therapeutic benefits of Ginkgo biloba L.: chemistry, efficacy, safety, and uses. Journal of Food Science, 73(1), 14–19.
- [19] RxMediaPharma, (2022), [online], Website https://portal.rxmediapharma.com.tr/ [accessed 25 May 2022].
- [20] Ma, G.L., Xiong, J., Yang, G.X., Pan, L.L., Hu, C.L., Wang, W., Fan, H., Zhao, Q.H., Zhang, H.Y., and Hu, J.F. (2016). Biginkgosides A–I, unexpected minor dimeric flavonol diglycosidic truxinate and truxillate esters from Ginkgo biloba leaves and their antineuroinflammatory and neuroprotective activities. Journal of Natural Products, 79(5), 1354–1364.
- [21] Beck, S., and Stengel, J. (2016). Mass spectrometric imaging of flavonoid glycosides and biflavonoids in Ginkgo biloba L. Phytochemistry, 130, 201–206.
- [22] Hasler, A., and Sticher, O. (1992). Identification and determination of flavonoids from Ginkgo biloba by high performance liquid chromatography. Journal of Chromatography A, 605(1), 41–48.
- [23] Liu, X.G., Yang, H., Cheng, X.L., Liu, L., Qin, Y., Wang, Q., Qi, L.W., and Li, P. (2014). Direct analysis of 18 flavonol glycosides, aglycones and terpene trilactones in Ginkgo biloba tablets by matrix solid phase dispersion coupled with ultra-high performance liquid chromatography tandem triple quadrupole mass spectrometry. Journal of Pharmaceutical and Biomedical Analysis, (97),123–128.
- [24] Lin, L.Z., Chen, P., Ozcan, M., and Harnly, J.M. (2008). Chromatographic profiles and identification of new phenolic components of Ginkgo biloba leaves and selected products. Journal of agricultural and food chemistry, 56(15), 6671–6679.
- [25] Van Beek, T.A., and Montoro, P. (2009). Chemical analysis and quality control of Ginkgo biloba leaves, extracts, and phytopharmaceuticals. Journal of Chromatography A, 1216(11), 2002–2032.
- [26] Rimmer, C.A., Howerton, S.B., Sharpless, K.E., Sander, L.C., Long, S.E., Murphy, K.E., Porter, B.J., Putzbach, K., Rearick, M.S., Wise, S.A., Wood, L.J., Zeisler, R., Hancock, D.K., Yen, J.H., Betz, J.M., Nguyenpho, A., Yang, L., Scriver, C., Willie, S., Sturgeon, R., Schaneberg, B., Nelson, C., Skamarack, J., Pan, M., Levanseler, K., Gray, D., Waysek, E.H., Blatter, A., and Reich, E. (2007). Characterization of a suite of ginkgo-containing standard reference materials. Analytical and Bioanalaytical Chemistry, 389(1), 179–96.
- [27] Chandra, A., Li, Y., Rana, J., Persons, K., Hyun, C., Shen, S., and Mulder, T. (2011). Qualitative categorization of supplement grade Ginkgo biloba leaf extracts for authenticity. Journal of Functional Foods, 3(2), 107–114.
- [28] Li,W., and Fitzloff, J.F. (2002). HPLC determination of flavonoids and terpene lactones ın commercıal Gınkgo bıloba products. Journal of Liquid Chromatography & Related Technologies, 25(16), 2501–2514.
- [29] Hasler, A., Sticher, O., and Meier, B. (1992). Identification and determination of the flavonoids from Ginkgo biloba by high-performance liquid chromatography. Journal of Chromatography A, 605(1), 41–48.
- [30] Kressmann, S., Muller, W.E., and Blume, H.H. (2002). Pharmaceutical quality of different Ginkgo biloba brands. Journal of Pharmacy and Pharmacology, 54(5), 661–669.
- [31] Booker, A., Frommenwiler, D., Reich, E., Horsfield, S., and Heinrich, M. (2016). Adulteration and poor quality of Ginkgo biloba supplements. Journal of Herbal Medicine, 6(2), 79–87.
- [32] Harnly, J.M., Luthria, D., and Chen, P. (2012). Detection of adulterated ginkgo biloba supplements using chromatographic and spectral fingerprints. Journal of AOAC International, 95(6), 1579–1587.
- [33] Liu, X.G., Wu, S.Q., Li, P., and Yang, H. (2015). Advancement in the chemical analysis and quality control of flavonoid in Ginkgo biloba. Journal of Pharmaceutical and Biomedical Analysis, 113, 212–225.
- [34] Wohlmuth, H., Savage, K., Dowell, A., and Mouatt, P. (2014). Adulteration of Ginkgo biloba products and a simple method to improve its detection. Phytomedicine, 21(6), 912–918.
- [35] López-Gutiérrez, N., Romero-González, R., Vidal, J.L.M., and Frenich, A.G. (2016). Quality control evaluation of nutraceutical products from Ginkgo biloba using liquid chromatography coupled to high resolution mass spectrometry. Journal of Pharmaceutical and Biomedical Analysis, 121, 151–160.
- [36] Tokalıoglu, S. (2012). Determination of trace elements in commonly consumed medicinal herbs by ICP-MS and multivariate analysis. Food Chemistry, 134(4), 2504–2508.
- [37] Zhao, L.J., Liu, W., Xiong, S.H., Tang, J., Lou, Z.H., Xie, M.X., Xia, B.H., Lin, L.M., and Liao, D.F. (2018). Determination of total flavonoids contents and antioxidant activity of Ginkgo biloba leaf by near-infrared reflectance method. International Journal of Analytical Chemistry, 2018, 1–7.
- [38] Li, C.Y., Lin, C.H., Wu, C.C., Lee, K.H., and Wu, T.S. (2004). Efficient 1H nuclear magnetic resonance method for improved quality control analyses of Ginkgo constituents. Journal of Agricultural and Food Chemistry, 52(12), 3721–3725.
- [39] Al‐kuraishy, H.M., Al‐Gareeb, A.I., Kaushik, A., Kujawska, M., and Batiha, G.E.S. (2022). Ginkgo biloba in the management of the COVID‐19 severity. Archiv der Pharmazie, 355, 2200188.
- [40] Czigle, S., Tóth, J., Jedlinszki, N., Radnai, E.H., Csupor, D., and Tekelová, D. (2018). Ginkgo biloba food supplements on the European Market –adulteration patterns revealed by quality control of selected samples. Planta Medica, 84, 475–482.
- [41] Slinkard, K., and Singleton, V.L. (1977). Total phenols analysis: Automation and comparison with manual methods. American Journal of Enology and Viticulture, 28, 49 – 55.
- [42] Kim, D.O., Jeong, S.W., and Lee, C.Y. (2003). Antioxidant capacity of phenolic phytochemicals from various cultivars of plums. Food Chemistry, 81(3), 321 – 326.
- [43] Park, Y.G., Kim, S.J., Jung, H.Y., Kang, Y.M., Kang, S.M., Prasad, D.T., Kim, S.W., and Choi, M.S. (2004). Variation of ginkgolides and bilobalide contents in leaves and cell cultures of Ginkgo biloba L. Biotechnology and Bioprocess Engineering, 9, 35-40.
- [44] Mesbah, M.K., Khalifa, S.I., Gindy, A.E., and Tawfik, KA. (2005). HPLC determination of certain flavonoids and terpene lactones in selected Ginkgo biloba L. Phytopharmaceuticals. Farmaco, 60(6-7),583-590.
- [45] Van Beek, T.A. (2005). Ginkgolides and bilobalide: their physical, chromatographic and spectroscopic properties. Bioorganic and Medicinal Chemistry, 13(17), 5001-5012.
- [46] Sevindik, O., Guclu, G., Agirman, B., Selli, S., Kadiroglu, P., Bordiga, M., Capanoglu, E., and Kelebek, H. (2022). Impacts of selected lactic acid bacteria strains on the aroma and bioactive compositions of fermented gilaburu (Viburnum opulus) juices. Food Chemistry, 378, 132079.
- [47] Fransen, H.P., Pelgrom, S.M.G.J., Stewart-Knox, B., de Kaste, D., and Verhagen, H. (2010). Assessment of health claims, content, and safety of herbal supplements containing Ginkgo biloba. Food and Nutrition Research, 54, 5221.
- [48] Chen, P., Ozcan, M., and Harnly, J. (2007). Chromatographic fingerprint analysis for evaluation of Ginkgo biloba products. Analytical and Bioanalytical Chemistry, 389(1), 251–61.
- [49] Demirezer, L.Ö., Büyükkaya, A., Uçaktürk, E, Uz, A.K., Güvenalp, Z., and Palaska, E. (2014). Adulteration determining of pharmaceutical forms of Ginkgo biloba extracts from different international manufacturers. Records of Natural Products, 8, 4, 394-400.
- [50] Dubber, M.J., and Kanfer, I. (2004). High-performance liquid chromatographic determination of selected flavonols in Ginkgo biloba solid oral dosage forms. Journal of Pharmaceutical Sciences, 24, 7(3), 303-309.