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Adulteration of Ginkgo biloba Leaf Extract
By
Stefan Gafner, PhD*
American Botanical
Council, 6200 Manor Road, Austin, TX 78723
*Corresponding
author: email
Keywords: adulterant, adulteration, Ginkgo biloba, ginkgo leaf extract,
Japanese pagoda tree, Japanese sophora, kaempferol, quercetin, rutin, Sophora japonica, Styphnolobium japonicum
Goal:
The goal of this bulletin is to provide timely information and/or updates on
issues of adulteration of ginkgo (Ginkgo
biloba) leaf and ginkgo leaf extracts to the international herbal industry
and extended natural products community in general. It is intended to give a
brief overview on the occurrence of adulteration, known adulterants and
analytical means to detect them, the market situation, and consequences for the
consumer and the industry.
1 General Information
1.1 Common name:
Ginkgo1
1.2 Other common names:
English: Maidenhair tree1,2
French: Ginkgo, arbre aux quarante écus, noyer du Japon3
German: Ginkgo, Fächerblattbaum, Mädchenhaarbaum,
Elefantenohrbaum, Tempelbaum3
Italian: Ginkgo, ginko, ginco,
albero di capelvenere
Spanish: Ginkgo, árbol sagrado, árbol de las
Pagodes, árbol de los quarantos escudos
Chinese: yin xing
(银杏)4
1.3 Accepted
Latin binomial: Ginkgo biloba L.1
1.4 Synonyms: Existing synonyms, e.g., Ginkgo macrophylla K.Koch, Salisburia biloba (L.) Hoffmanns., or
Salisburia macrophylla Reyn.,5 are no longer used in science or in commerce.
1.5
Botanical family: Ginkgoaceae
1.6
Plant part: Two parts
of the ginkgo tree are sold on the market, the leaf and the seed.
This
bulletin focuses mainly on the ginkgo leaf extract characterized by 24%
flavonol glycosides and 6% triterpenes, which has been subject to repeated and
increasing levels of adulteration over the past decades. Products derived from
the seeds are not addressed in this document.
1.7
General use(s): Ginkgo leaf extract is used to improve mental performance, increase
the pain-free walking distance in peripheral arterial occlusive disease, and
for vertigo and tinnitus.6-8 Other indications include (age-associated) cognitive
impairment and quality of life improvement in patients with mild dementia.6,8,9 Ginkgo leaf extracts may help to prevent symptoms
related to altitude sickness.10,11
2 Market
2.1 Importance
in the trade: In the
United States, ginkgo is mainly sold in the Mainstream Multi-Outlet channel
(previously referred to as the Food, Drug and Mass Market channel) where it has
ranked among the top 25 best-selling dietary supplements from 2009-2014, with
sales between US $11.1 and $16.0 million (excluding sales at Walmart). Sales in
this channel have slightly increased in 2015 and 2016, but the sales rank has
dropped to number 23 at the same time (Table 1). Sales in the Natural channel
were between US $3.9 and $4.7 million (excluding sales at Whole Foods) in the
same time frame, ranking ginkgo at numbers 15-20 in the years between 2009 and 2016.12-18 Sales figures from the Nutrition Business Journal ranked ginkgo at #13 of herbal dietary
supplements in the United States in 2011, with overall sales of US $90 million.19 Total worldwide sales of ginkgo
products in 2012 were US $1.26 billion, with China accounting for 46% (US $578
million) of the sales, Germany for 12% (US $152 million), Australia for 4.8%
(US $61 million), France for 4.2% (US $53 million), and Brazil for 3.8% (US $48
million).20
Table
1: Sales data for ginkgo dietary supplements from 2013–2016
Channel
|
2013
|
2014
|
2015
|
2016
|
|
Rank
|
Sales [US$]
|
Rank
|
Sales [US$]
|
Rank
|
Sales [US$]
|
Rank
|
Sales [US$]
|
Naturala
|
20
|
3,988,705
|
18
|
4,076,228
|
17
|
4,659,417
|
20
|
4,598,986
|
Mainstream
Multi-Outletb
|
19
|
11,488,186
|
19
|
11,147,066
|
22
|
12,810,392
|
23
|
12,917,783
|
aAccording
to SPINS; This includes data from co-ops, associations, independent retailers, and large regional
chains. These data do not include sales data from Whole Foods
Market, nor does it capture non-electronic tracking systems such as sales
through health professionals, private internet distributors, and many health
food stores.
bAccording to SPINS/IRI; This
channel coverage includes the food, drug, and mass-market sector, military
commissaries, and select buyer’s clubs and so-called dollar stores. SPINS/IRI
data does not include discount department store sales, e.g., possible sales at
Walmart and club stores are excluded)
Sources:
Smith T, et al.18 T. Smith (American
Botanical Council) e-mail to S. Gafner, September 2, 2015 and September 3,
2015. K. Kawa (SPINS) e-mail to S. Gafner, July 11, 2016.
2.2 Supply
sources: The majority
of the ginkgo extracts on the market are made from leaves cultivated on plantations
in China (Jiangsu, Shandong, Zhejiang, Hubei, Anhui, and Guangxi provinces),
France, and the United States.6 Other ginkgo plantations are found in
Australia, Korea, Japan and New Zealand. (H. Wohlmuth [MediHerb/Integria
Healthcare] e-mail communication, September 25, 2015) In China, ginkgo trees
are cultivated in small family farms under the supervision of the local
Government.21
2.3 Raw
material and finished product forms:
Whole, cut, and powdered dry leaf, dry leaf extracts, and liquid leaf extracts
(e.g., tinctures). The extracts are primarily quantified to contain 24%
flavonol glycosides and 6% terpene lactones (24/6), based on the widely clinically
tested extract EGb 761®, manufactured by Willmar Schwabe GmbH &
Co. KG (Karlsruhe, Germany). The Schwabe extract is patented and follows a
complex production process: the leaves are harvested from plantations only when
chemical tests show the flavonoid content at a maximum. When the leaves have
lost 75% of their weight after the drying process, they are subjected to an
acetone-water (6:4) extraction. Successive treatments are used to remove other,
less desirable compounds (e.g., ginkgolic acids). The extract is eventually
concentrated (30–70:1), and quantified to the labeled content.3 There are many other dry extracts
that use a manufacturing process different from the EGb 761 on the market;
additionally, a number of liquid extracts are sold, which are usually made
using water-alcohol mixtures at various ratios; with some exceptions, these
ginkgo preparations are not the subject of published human clinical trials.
2.4
Market dynamics: Statistics
on the annual production volume of ginkgo leaves are difficult to find and the
available numbers show some discrepancies. According to a review on ginkgo
published in 2008, the production of ginkgo leaves from China, France, and the United
States (specifically, South Carolina) was approximately 8,000 metric tons.22 However, another report in 2008 estimated
the yearly production in China alone at 20,000 metric tons.23 Global demand for dried ginkgo leaves
was estimated at 60,000 metric tons in 2014.24 Between 2009 and 2016, the sales of
ginkgo supplements in the United States have been relatively flat, or even
declining, at least in the Mainstream Multi-Outlet channel.12-17 However, global demand in leaf extracts has seen a
consistent growth from US $118 million in 2013 to US $162 million in 2016.25 Given that the supply chain and
market for ginkgo seem fairly steady, it is not likely that the factors
underlying ginkgo adulteration are due to changing market dynamics.
3 Adulteration
3.1 Known
adulterants: The main
concern with ginkgo adulteration is the addition of pure flavonols/flavonol
glycosides or extracts from other botanicals which are rich in flavonol
glycosides:
Pure
flavonols:
Flavonol
glycoside-rich extracts:
- Styphnolobium japonicum (L.) Schott, (syn: Sophora japonica L., Fabaceae)
- Fagopyrum
esculentum Moench, Polygonaceae
A different type of issue was
evidenced in regulatory actions by the Chinese
government in 2015,
which took actions against companies that allegedly adulterated ginkgo extracts
by using 3% hydrochloric acid instead of the more expensive organic solvents
(ethanol, acetone) in the manufacturing process of ginkgo extracts, providing
extracts with higher amounts of free quercetin, kaempferol, and isorhamnetin.26 The use of unconventional solvents in
the manufacturing process also raises the question of just how similar the
phytochemical composition of some 24/6 extracts from China are to the
clinically tested EGb 761 extract. This is especially relevant considering the
active constituents of ginkgo extract are not well defined.
3.2 Sources
of information supporting confirmation of adulteration:
There is ample evidence of the
production and sale of adulterated ginkgo extracts in the international supply
chain.
In 2003, an investigation of the
quality of nine commercial ginkgo extracts from suppliers in Europe, Asia, and
North America found one sample with an unusually high content of rutin, a
flavonol glycoside that occurs in many plant species, and one sample with
almost no ginkgo terpene lactones and no ginkgo flavonols. The authors
suggested that pure rutin was added to one sample to increase the contents of
total flavonols.27
Similarly, four out of 14 commercial
ginkgo products sourced in the Edmonton, Alberta (Canada) area were likely
adulterated with pure flavonols (rutin, quercetin, kaempferol, and
isorhamnetin),28 and in a comparison of
high-performance liquid chromatography (HPLC) fingerprints of ginkgo extracts
from 19 suppliers from the Jiangsu and Zhejiang provinces in China, three
products were found to be adulterated with exogenous rutin.29 Whether the deviations in
concentrations of quercetin, kaempferol, and isorhamnetin are indeed due to spiking of ginkgo extracts
with synthetic flavonols, as
suggested by Liu et al.,28 is an issue that has been questioned by experts. Higher amounts of these flavonols,
which are present in only trace amounts in fresh ginkgo leaves, may be found in
an extract due to an unusual manufacturing process or improper storage (H.
Wohlmuth e-mail communication, September 27, 2015).
The issue of ginkgo adulteration was
again raised in a presentation by Kurth in 2008. In this presentation, rutin
(sourced from buckwheat [F. esculentum]
or Japanese sophora [S. japonicum],
also known as Japanese pagoda tree), and/or quercetin, and/or kaempferol were
found as adulterants of ginkgo extracts.30
In 2010, the German Central Laboratory
for Pharmacists (Zentrallaboratorium Deutscher Apotheker) investigated 10
ginkgo food supplements purchased in Germany. The researchers calculated the
quercetin/(kaempferol + isorhamnetin) ratio after hydrolysis, and found a range
of 0.8 – 1.2 for authentic ginkgo leaf material. However, in seven of the ten
commercial samples, the ratio was above 1.7 (1.78 – 7.70), suggesting that these
products were adulterated.31
The adulteration of ginkgo extracts
with pure flavonoids or flavonoid-rich extracts was also detailed in 2011. In
this study, Chandra et al. reported that chromatographic profiles of three out
of eight products labeled to contain ginkgo extracts closely resembled those of
commercial extracts obtained from Japanese sophora. The HPLC chromatogram of
the unhydrolyzed products at 370 nm of the particular commercial sophora fruit
extract showed rutin as a single peak, while quercetin was the main peak in the
commercial sophora flower extract. Isoflavonoids from sophora, like genistein and
its glycosides that are proposed by some experts as markers for adulteration,
barely absorb at 370 nm, and may therefore go undetected.32
A study in Japan looked at 22
commercial products (16 ginkgo products from Japan and six from Germany and
France) by HPLC-UV/MS without prior hydrolysis, finding three products with
unusually high amounts of quercetin.33
Also in 2012, Harnly et al. analyzed
18 ginkgo dietary supplements purchased in the Beltsville, MD area or from the internet.
Comparison of chromatographic and spectral fingerprints with authentic ginkgo
extract led to the conclusion that seven products were clearly adulterated with
either rutin, quercetin, or an unidentified flavonol glycoside.34
Adulteration of commercial ginkgo
products with rutin purchased in the Turkish market was reported by Demirezer
in 2014.35
In 2014, Australian researchers
published a relatively simple method to detect adulteration of ginkgo extract
in commercial dietary supplement products. The authors
discovered admixtures of the free flavonols quercetin and kaempferol without
prior hydrolysis in three of the eight commercial samples that were analyzed.
The three adulterated samples also contained genistein, an isoflavone that is
characteristic of some plants in the pea family (Fabaceae), as noted above. The
authors hypothesize that the genistein could have come from extracts of the
fruit of Japanese sophora.36
Clear evidence of ginkgo adulteration
with Japanese sophora extracts was provided in a study by Avula et al., where 11
out of 25 tested supplements, purchased online from suppliers in the United
States, showed flavonol-glycosides that are typically found in S. japonica fruit, such as genistein-4’-O-glucoside and genistein-4’-O-neohesperidoside.37
The authenticity of bulk standardized
ginkgo leaf extracts (n = 15) and commercial finished ginkgo products (n = 14)
were also investigated by Canadian researchers Ma et al. in 2016. The powdered
extracts were received from various Canadian suppliers, and commercial samples
were purchased in local pharmacies in Canada (n = 7) or China (n = 7). Based on
comparison of the HPLC-UV fingerprints with those of authentic samples, occurrence
of adulteration was confirmed in four of 15 (27%) bulk standardized extracts
and 10 of 14 (71%) finished commercial products.38
An analysis of 20 batches of ginkgo
extract from one manufacturer in Jiangsu province, China was conducted by Chinese
researchers in 2016. The samples were analyzed by HPLC-UV with subsequent
multivariate statistical evaluation; 17 batches could be separated into two
clusters according to their phytochemical composition, with three samples not
clustering within either of these two clusters. Of these three batches, one
batch was adulterated, based on the presence of genistin and genistein, one
contained unusually high amounts of quercetin, kaempferol, and isorhamnetin,
and one had lower amounts of many of the ginkgo compounds overall.39
Another report on ginkgo quality was
published by Booker et al.40 The 35 food supplements analyzed in
this study were obtained from health food stores, supermarkets, and pharmacies
in the area of Central London, UK, and from the internet. Samples were analyzed
by high-performance thin-layer chromatography (HPTLC), or proton nuclear
magnetic resonance (1H NMR) with subsequent principal component
analysis (PCA) using soft independent modeling by class analogy (SIMCA)
software. Of the 35 samples, 33 (94%) exhibited elevated levels of rutin (n = 8)
and/or quercetin (n=26), or low levels of ginkgo metabolites when compared to
reference samples. One sample did not have any ginkgo, but contained a compound
with structural similarity to 5-hydroxytryptophan.
López-Gutiérrez et al. analyzed 11
commercial finished ginkgo products purchased in local stores in Almeida,
Spain, and Krakow, Poland.41 The authors found the characteristic terpene lactones in
all products, and ginkgolic acids in 10 out of 11 ginkgo supplements. However,
they also found unusually high concentrations (27.2 – 38.2 mg/g) of rutin in three
products, and isoflavonoid (predominantly genistein) concentrations between
0.02 and 2.41 mg/g.41 Of particular interest, these authors reported the
presence of glycitein in addition to genistein in two products. Glycitein is
known from a number of plants from the family Fabaceae, including Japanese sophora.
Evaluation of 18 commercial ginkgo
supplements from the North American and European markets, obtained between 2015
and 2017, by reverse phase HPTLC and HPLC-UV (detection at 370 and 260 nm) by
NSF International showed that only three products contained authentic ginkgo
leaf extracts. Adulteration included uncharacteristically high levels of rutin,
quercetin, kaempferol, or extracts from Japanese sophora or green tea. (M. Pan
[NSF International] email communication, October 25, 2017)
3.3 Genistein
controversy: Many
researchers have suggested that the isoflavone genistein can be used as a
marker to detect adulteration with extracts of Japanese sophora.
However, other authors have reported
that genistein is a genuine constituent in ginkgo leaf, albeit at very small
amounts.42-44 Yao et al. (2017) reported genistein concentrations
between 5-28 μg/g dry leaf using a validated HPLC-UV method with detection at
350 nm. The HPLC conditions allowed for a clear separation between genistein
and apigenin, two compounds that have the same molecular weight and may be
confused even if an MS detector is used. The amounts of genistein in the leaves
was dependent on the season, and was found to be highest in September and
October.44 Genistein has also been reported from
leaf extracts45-48 but since ginkgo extract adulteration is widespread,
questions about the authenticity of the materials used in these studies remain.
While genistein is known to occur in S. japonica, the majority of
investigations into the chemistry of ginkgo failed to detect this isoflavone.49 In addition, the enzyme isoflavone synthase, which is
needed to produce isoflavones biosynthetically, has not been reported from
ginkgo. Another aspect to consider is the absence of isoflavone glycosides in
authentic ginkgo leaves. Since flavonoids in ginkgo are predominantly found as
glycosides — e.g., rutin is present in much larger concentrations compared to
quercetin — one would expect genistein glycosides (such as genistin) to occur
in larger amounts than genistein. On the other hand, biflavones reportedly are
mainly found as aglycones, so it cannot be excluded that the same could be true
for the isoflavones.
A recent investigation into the
question of genistein occurrence in six samples of authentic ginkgo whole leaf
material by four separate analytical laboratories (two academic laboratories,
one contract analytical laboratory, and one in-house research laboratory at a
dietary supplement supplier) by HPLC-MS gave contradictory results, with
genistein not detected in two laboratories, while the other two either reported
it as “detected” or to occur at concentrations between 37 – 217 ng/g dry leaf (Gafner
S, unpublished results). If present in ginkgo leaves, genistein is found at low
concentrations. Therefore, establishing a maximal acceptable limit for
genistein could be a way to distinguish authentic ginkgo materials from those
containing extracts of S. japonica. A
limit of 1% sophoricoside (genistein-4'-O-glucoside)
in ginkgo extracts was set in 2015 by the Chinese Food and Drug Administration.50 Sophoricoside is a marker compound
for the presence of Japanese sophora fruit extracts.
3.4
Accidental or intentional adulteration: Industry experts agree that the adulteration of ginkgo
extracts is intentional, due to the financial advantage of adding cheaply-sourced
flavonols like rutin or quercetin. According to William Obermeyer, PhD, former
FDA natural products chemist and former technical director of ConsumerLab.com,
the costs for a Ginkgo biloba extract
in 2009 varied between $35-$90/kg, while the price of rutin isolated from buckwheat
is ca. $10/kg, giving an incentive for adulteration to unscrupulous suppliers
and manufacturers.51 Herrmann Kurth, PhD, director of
quality control at Finzelberg GmbH & Co. KG, places the cost for the
EGb 761 extract at >200€/kg (US $220 at the exchange rate from July 8, 2015),
making lower-cost sources to boost flavonol glycoside contents attractive to less
scrupulous companies.30 Costs in 2015 for ginkgo extracts
from Chinese manufacturers ranged between US $150-240/kg, while Japanese
sophora flower extracts sold for US $30/kg (J. Xie, Y-C Ma, J. Zhang [Canadian
Phytopharmaceutical Corp.] oral communications, October 7, 2015). Jay Lee, PhD,
president of Beijing Ginkgo Group, said in an interview that “The vast majority
of the prices we’re up against in the U.S. market do not even support the cost
of the raw materials used to manufacture a high quality ginkgo extract. Most
contract manufacturers tell us they are simply meeting their customer’s
specifications, so if the customer simply states 24/6 [24% flavonoids/6%
terpenes], then the contract manufacturer will seek the lowest cost 24/6.”52 Conversely, manufacturers unaware of
the complexity of ginkgo analysis may unknowingly incorporate adulterated
ginkgo extracts into their products, depending on either internal or external
analysis that confirm the constituent profile desired, namely 24% flavonol
glycosides and 6% diterpene lactones. At the same time, knowledge of ginkgo
extract adulteration has been reported for two decades. Therefore, if a
supplier or contract manufacturer does not take steps to ensure the extract
they are selling or buying is made from authentic ginkgo leaves and is free of
adulterations as outlined in this bulletin, they are likely entering
adulterated products into trade and are subject to the liability that their
actions entail.
3.5 Frequency of occurrence: There are no reliable comprehensive data
on the number of adulterated ginkgo products on the market. Most of the
published studies included only a small number of samples. The largest study on
commercial ginkgo supplements evaluated 40 products using DNA mini-barcodes. In
this study, DNA was retrieved in 37 products, and 31 of these 37 products (84%)
contained ginkgo DNA. However, since the DNA barcoding is unable to detect pure
isolates, and the author did not use specific primers to detect DNA from
Japanese sophora, or any other potential adulterant, the addition of pure
flavonols, or flavonol-rich materials would have gone undetected.53 The largest studies specifically
looking at admixture of flavonols from origins other than ginkgo leaf found
adulteration rates of 14% (three of 22 samples), 48% (10 of 21 samples), 44%
(11 of 25) and 48% (14 of 29 samples).33,37,38,54 In the study by Avula et al., eight additional samples
(32%) contained variable amounts of genistein, a proposed marker compound for
ginkgo adulteration (although the presence of genistein could be also due to
soy-based excipients, which would not be considered a case of adulteration),
increasing the number of potentially adulterated products to 76%.37 Finally, an investigation initiated
by the British Broadcasting Corporation (BBC), which linked up with a research
team of the University College of London’s College of Pharmacy, concluded that many
ginkgo food supplements had little or
no ginkgo extract in them.55 (Food supplements are regulated in
the European Union under different quality control requirements than
“Traditional Herbal Remedies,” which are a type of drug, requiring higher
quality assessments for identity and authenticity.) Additional details of this
study were published in 2016. Of the 35 food supplements analyzed, 26 (74%)
contained elevated levels of rutin and/or quercetin, and one sample did not
contain any chemistry consistent with ginkgo at all.40
3.6
Possible therapeutic issues:
The admixture of pure rutin, quercetin, kaempferol, isorhamnetin, or extracts
of flavonol-rich plant materials is not considered a safety concern. However,
the adulterated products are not phytoequivalent to the EGb 761 extract, or
other clinically tested ginkgo products. In addition, adulterated low quality
ginkgo extracts may contain higher concentrations of less desirable ginkgo leaf
constituents, e.g., ginkgolic acids, which are known contact allergens and have
shown to cause contact dermatitis.56 (Ginkgolic acid levels are required
to be no more than 5 ppm [μg/g] in the European
Pharmacopoeia [Ph. Eur] and the
United States Pharmacopeia [USP]).57,58
3.7
Analytical methods to detect adulteration: Most often, extracts of ginkgo in bulk or finished
products are analyzed by HPLC using evaporative light scattering (ELSD) or mass
spectrometric (MS) detection for the terpene lactones, and ultraviolet
detection (UV) at 370 nm for the flavonols. Since ginkgo leaves contain over 20
flavonols, predominantly glycosides of quercetin, kaempferol, and isorhamnetin,
the total flavonol content is generally measured after hydrolysis, which
cleaves the sugar portion from the flavonol aglycone, greatly simplifying the
analysis to the quantification of quercetin, kaempferol, and isorhamnetin. Thus,
although the 24/6 specification in pharmacopeias refers to 24% flavonol glycosides, the prescribed analytical
methods quantify the free aglycones that form as a result of hydrolysis. Accordingly,
since glycosides of quercetin, kaempferol, and isorhamnetin are found in many
plants, materials that are particularly rich in these flavonols can potentially
be added to ginkgo in order to increase the flavonol content.
Once
the hydrolysis reaction is performed, signs of adulteration become less
obvious. The American Herbal Pharmacopoeia monograph lists the typical ratio of
quercetin, kaempferol, and isorhamnetin in ginkgo leaf extracts after
hydrolysis as between 6:5:1 and 5:4:1.6 In order to prevent the adulteration
of ginkgo extracts with extraneous flavonols, the USP adopted criteria in 2012 for
the kaempferol to quercetin (not less than 0.7) and isorhamnetin to quercetin
(not less than 0.1) peak ratios after hydrolysis.59 Despite this, some manufacturers have
found ways to fraudulently spike ginkgo extracts while complying with the USP
criteria.36 Therefore, the USP monograph for Powdered Ginkgo Extract now includes an
additional test: Limit of Rutin and
Quercetin, which specifies maxima of 4% for rutin and 0.5% for quercetin in
unhydrolyzed extracts.58,60
In
May 2013 the California company Ethical Naturals, Inc. issued the report
“Ginkgo Adulteration & Identification with Fructus sophorae (Sophora japonica)”, a revised version of
its 2006 report on ginkgo adulteration, which suggests the use of HPLC with an
UV detection wavelength of 260 nm in addition to 360 nm as a means to detect
genistein.48
Other
HPLC-UV methods propose to measure the entire chemical composition without
hydrolysis and compare this HPLC fingerprint to a fingerprint of authentic ginkgo
leaves.32,34,38 Wohlmuth et al. suggest using the HPLC conditions
outlined in the USP and analyzing the ginkgo extracts before and after
hydrolysis in order to detect admixture of pure flavonol aglycones, and to test
for the presence of genistein.36 Other identity tests use HPTLC for
identification,37,57,58 but the admixture of pure flavonols may be difficult to
detect. However, this technique has proven successful in the detection of
spiking with fruit or flower extracts from Japanese sophora.37 An additional
derivatization step added to the original HPTLC method for identification was presented
in 2017 by Frommenwiler et al. Besides added rutin and/or quercetin, the
modified method allows the detection of buckwheat and Japanese sophora fruit or
flower extracts.61
Finally,
a comparison among HPLC-UV, UV spectrophotometry, and near infrared (NIR)
spectroscopy with subsequent statistical evaluation by multivariate statistical
analysis concluded that UV spectrophotometry was more sensitive to minor
variations in the chemical composition than HPLC-UV. The NIR approach was not
able to distinguish between authentic and adulterated samples since the
excipients, which are part of a solid-state NIR spectrum, have a significant
impact on the final result.34
3.8 Perspectives: In the report on ginkgo adulteration published by Natural Products
Insider, a dietary supplement industry trade publication, William Obermeyer,
PhD looked back at ginkgo dietary supplement testing at ConsumerLab. Based on tracking of the kaempferol
to quercetin ratios, he suggested that the quality of ginkgo products worsened over the years from 1999 to 2007. In the same article, Jochen
Muehlhoff, PhD, former Marketing Information Manager at Willmar Schwabe GmbH
& Co. KG, called the adulteration of ginkgo extracts a global problem,
though he noted that it is less of a problem in Europe, but definitely a
problem in the United States, and even more pronounced in some Asian countries.
4 Conclusions: Economically motivated adulteration of
ginkgo extracts with pure flavonol-glycosides, flavonols, or flavonol-rich
extracts of other species is an ongoing problem in the dietary supplement
industry and elsewhere. While the addition of flavonols is not considered a
safety problem, the health benefits of sub-standard ginkgo extracts spiked with
pure flavonols or flavonol-rich extracts have not been established. The
addition of extraneous flavonols can be detected by HPLC with UV or MS
detection. Considering this adulteration has been reported for decades and that
methods for the detection of adulteration have been available, there is little
excuse for this to continue to occur. It is suggested that contract
manufacturers, independent analytical laboratories, and manufacturers with
internal analytical capabilities need to take the lead in preventing low-cost
adulterated extracts from unscrupulous extract manufacturers, most of which
appear to originate from China, from entering the global market.
5 References
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Leung AY, Tucker AO. Herbs of Commerce.
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- Gruenwald
J, Brendler T, Jaenicke C. PDR for Herbal
Medicines. 2nd ed. Montvale, NJ:
Medical Economics Co; 2000.
- Wichtl
M. Ginkgo folium – Ginkgo leaf. In: Wichtl M, ed. Herbal Drugs and Phytopharmaceuticals. 3rd ed. Stuttgart, Germany:
Medpharm Scientific Publishers; 2004.
- Flora
of China. Missouri Botanical Garden & Harvard University Herbaria. Available
at: http://www.efloras.org/florataxon.aspx?flora_id=2&taxon_id=200028370.
Accessed May 25, 2017.
- Ginkgo biloba. The Plant List. Version
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