Planta Med 2018; 84(06/07): 475-482
DOI: 10.1055/a-0581-5203
Natural Product Chemistry and Analytical Studies
Original Papers
Georg Thieme Verlag KG Stuttgart · New York

Ginkgo biloba Food Supplements on the European Market – Adulteration Patterns Revealed by Quality Control of Selected Samples

Szilvia Czigle
1   Comenius University in Bratislava, Faculty of Pharmacy, Department of Pharmacognosy and Botany, Bratislava, Slovak Republic
,
Jaroslav Tóth
1   Comenius University in Bratislava, Faculty of Pharmacy, Department of Pharmacognosy and Botany, Bratislava, Slovak Republic
,
Nikoletta Jedlinszki
2   University of Szeged, Faculty of Pharmacy, Institute of Pharmacognosy, Szeged, Hungary
,
Erzsébet Háznagy-Radnai
2   University of Szeged, Faculty of Pharmacy, Institute of Pharmacognosy, Szeged, Hungary
,
Dezső Csupor
2   University of Szeged, Faculty of Pharmacy, Institute of Pharmacognosy, Szeged, Hungary
,
Daniela Tekeľová
1   Comenius University in Bratislava, Faculty of Pharmacy, Department of Pharmacognosy and Botany, Bratislava, Slovak Republic
› Author Affiliations
Further Information

Publication History

received 01 June 2017
revised 15 February 2018

accepted 16 February 2018

Publication Date:
05 March 2018 (online)

Abstract

The aim of this study was to prove whether Ginkgo biloba food supplements on the European market comply with pharmaceutical quality, and whether their composition satisfies the European Pharmacopoeia criteria. Medicinal products containing a standardised Ginkgo leaf extract are used for the improvement of cognitive impairment and quality of life in mild dementia. Further, Ginkgonis folium is used for the treatment of peripheral circulation disorders. Pharmacopoeial Ginkgo dry extract contains 22.0 – 27.0% flavonoids and 5.4 – 6.6% terpene lactones (ginkgolides, bilobalide). In addition to its widespread use as an herbal medicine (herbal medicinal product), the same extract can be an ingredient in food supplements. The content of active secondary metabolites was quantified in a number of European food supplements containing Ginkgo dry extract or Ginkgo leaf. Flavonoids were quantified using a modified pharmacopoeial HPLC-UV method, and terpene lactones (ginkgolides A, B, C, and bilobalide) using LC-MS/MS. Some Ginkgo leaf supplement samples were also analysed by microscopy. The quality of food supplements on the European market is dubious. In this paper, we present selected examples of several methods of adulteration and falsification, including higher/lower doses of Ginkgo dry extract or Ginkgo leaf than declared and the addition of undeclared extraneous materials. These examples reveal several patterns in the manufacturing of adulterated products.

Supporting Information

 
  • References

  • 1 Bensky D, Gamble A, Bensky LL. Chinese herbal Medicine Materia Medica. Washington: Eastland Press; 1986
  • 2 Czigle S. Pharmacognostic analysis of Ginkgo biloba L. [habilitation thesis]. Bratislava: Comenius University in Bratislava, Faculty of Pharmacy; 2013: 217
  • 3 Committee on Herbal Medicinal Products (HMPC). European Union herbal monograph on Ginkgo biloba L., folium. EMA/HMPC/321097/2012. Available at. http://www.ema.europa.eu/docs/en_GB/document_library/Herbal_-_Community_herbal_monograph/2015/04/WC500185243.pdf Accessed February 28, 2018
  • 4 van Beek TA, Bombardelli E, Morazzoni P, Peterlongo F. Ginkgo biloba L. Fitoterapia 1998; 69: 195-245
  • 5 Hasler A, Sticher O. Identification and determination of the flavonoids from Ginkgo biloba by high-performance liquid chromatography. J Chromatogr 1992; 605: 41-48
  • 6 Hasler A, Meier B. Ginkgo biloba – content of flavonoids and terpenes from leaves during the harvest time and from full extracts determined by chromatographic and biological methods. Planta Med 1993; 59: A632
  • 7 Hasler A, Gross GA, Meier B, Sticher O. Complex flavonol glycosides from the leaves of Ginkgo biloba . Phytochemistry 1992; 31: 1391-1394
  • 8 Hasler A, Meier B, Sticher O. Botanische, analytische und pharmakologische Aspekte. Ginkgo biloba . Schweiz Apoth Ztg 1990; 128: 341-347
  • 9 Hasler A, Sticher O, Meier B. High-performance liquid chromatographic determination of five widespread flavonoid aglycones. J Chromatogr 1990; 508: 236-240
  • 10 Vanhaelen M, Vanhaelen-Fastré R. Flavonol triglycosides from Ginkgo biloba . Planta Med 1989; 55: 202
  • 11 van Beek TA. Chemical analysis of Ginkgo biloba leaves and extracts. J Chromatogr A 2002; 967: 21-55
  • 12 Van Beek TA, Lankhorst PP. Confirmation of the C-1 stereochemistry of ginkgolides by NMR. Tetrahedron 1996; 52: 4505-4514
  • 13 van Beek TA, Lelyveld GP. Concentration of ginkgolides and bilobalide in Ginkgo biloba leaves in relation to the time of year. Planta Med 1992; 58: 413-416
  • 14 van Beek TA, Lelyveld GP. Preparative isolation and separation procedure for ginkgolides A, B, C and J and bilobalide. J Nat Prod 1997; 60: 735-738
  • 15 van Beek TA, Scheeren HA, Rantio T, Melger WC, Lelyveld GP. Determination of ginkgolides and bilobalide in Ginkgo biloba leaves and phytopharmaceuticals. J Chromatogr 1991; 543: 375-387
  • 16 van Beek TA, Wintermans MS. Preparative isolation and dual column high-performance liquid chromatography of ginkgolic acids from Ginkgo biloba . J Chromatogr A 2001; 930: 109-117
  • 17 Huh H, Singh J, Staba EJ. Ontogenic aspects of Ginkgo polyprenols. Planta Med 1993; 59: 379-380
  • 18 Chen P, Su XL, Nie LH, Yao SZ, Zeng JG. Analysis of ginkgolides and bilobalides in Ginkgo biloba L. high-performance liquid chromatography. J Chromatogr Sci 1998; 36: 197-200
  • 19 DeFeudis FV. Ginkgo biloba Extract (EGb 761): pharmacological Activities and clinical Applications. Paris: Elsevier; 1991
  • 20 Ginkgo leaf. European Pharmacopoeia 9. Strasbourg: Council of Europe; 2017: 01/2011:1828
  • 21 Ginkgo dry extract, refined and quantified. European Pharmacopoeia 9. Strasbourg: Council of Europe; 2017: 04/2008:1827
  • 22 Directive 2011/62/EU of the European Parliament and of the Council of 8 June 2011 amending Directive 2001/83/EC on the Community code relating to medicinal products for human use, as regards the prevention of the entry into the legal supply chain of falsified medicinal products. Available at. http://data.europa.eu/eli/dir/2011/62/oj Accessed February 28, 2018
  • 23 Decree No. 225/2008 Coll., laying down requirements on food supplements and enrichment of foodstuffs. Available at. http://www.mvcr.cz/soubor/sb071-08-pdf.aspx Accessed October 5, 2017
  • 24 Directive 2002/46/EC of the European Parliament and of the Council of 10 June 2002 on the approximation of the laws of the Member States relating to food supplements. Available at. http://data.europa.eu/eli/dir/2002/46/oj Accessed February 28, 2018
  • 25 European Food Safety Authority: Register of questions. Available at. http://registerofquestions.efsa.europa.eu/roqFrontend/ Accessed October 5, 2017
  • 26 Sticher O. Quality of Ginkgo preparations. Planta Med 1993; 59: 2-11
  • 27 Ding S, Dudley E, Plummer S, Tang J, Newton RP, Brenton AG. Fingerprint profile of Ginkgo biloba nutritional supplements by LC/ESI-MS/MS. Phytochemistry 2008; 69: 1555-1564
  • 28 Wagner H, Bladt S, Hartmann U, Daily A, Berkulin W. Ginkgo biloba (DC- und HPLC-Analyse von Ginkgo-Extrakten und Ginkgo-Extrakte enthaltenden Phytopräparaten). Dtsch Apoth Ztg 1989; 129: 2421-2429
  • 29 Dubber MJ, Kanfer I. Determination of terpene trilactones in Ginkgo biloba solid oral dosage forms using HPLC with evaporative light scattering detection. J Pharm Biomed Anal 2006; 42: 135-140
  • 30 Dubber MJ, Sewram V, Mshicileli N, Shephard GS, Kanfer I. The simultaneous determination of selected flavonol glycosides and aglycones in Ginkgo biloba oral dosage forms by high-performance liquid chromatography-electrospray ionisation-mass spectrometry. J Pharm Biomed Anal 2005; 37: 723-731
  • 31 Chen P, Ozcan M, Harnly J. Chromatographic fingerprint analysis for evaluation of Ginkgo biloba products. Anal Bioanal Chem 2007; 389: 251-261
  • 32 Wohlmuth H, Savage K, Dowell A, Mouatt P. Adulteration of Ginkgo biloba products and a simple method to improve its detection. Phytomedicine 2014; 21: 912-918
  • 33 Rimmer CA, Howerton SB, Sharpless KE, Murphy KE, Porter BJ, Putzbach K, Rearick MS, Wise SA, Wood LJ, Zeisler R, Hancock DK, Yen JH, Betz JM, NguyenPho A, Yang LL, Scriver C, Willie S, Sturgeon R, Schaneberg B, Nelson C, Skamarack J, Pan M, Levanseler K, Gray D, Wayse EH, Blatter A, Reich E. Characterization of a suite of ginkgo-containing standard reference materials. Anal Bioanal Chem 2007; 389: 179-196
  • 34 Košťálová D, Tekeľová D, Czigle S, Tóth J, Mrlianová M, Lalkovič Š. The content of flavonoids in selected drug formulations containing Ginkgo biloba . Farm obzor 2005; 74: 119-123
  • 35 Avula B, Sagi S, Gafner S, Upton R, Wang YH, Wang M, Khan IA. Identification of Ginkgo biloba supplements adulteration using high performance thin layer chromatography and ultra high performance liquid chromatography-diode array detector-quadrupole time of light-mass spectrometry. Anal Bioanal Chem 2015; 407: 7733-7746
  • 36 Czigle S, Tekeľová D, Tóth J, Mrlianová M. Variability of flavonoid content in leaves of young trees of Ginkgo biloba L. during a vegetation period. Farm obzor 2011; 80: 169-175
  • 37 Tekeľová D, Tóth J, Mrlianová M, Czigle S, Filippová D, Grančai D. Quantitative determination of flavonoids in autumnal leaves of Ginkgo biloba L. using spectrophotometric and HPLC methods. Farm obzor 2006; 75: 272-279
  • 38 Harnly JM, Luthria D, Chen P. Detection of adulterated Ginkgo biloba supplements using chromatographic and spectral fingerprints. J AOAC Int 2012; 95: 1579-1587