Добавил:
Sekretar
kiopkiopkiop18@yandex.ru
t.me/Prokururor I Вовсе не секретарь, но почту проверяю
Опубликованный материал нарушает ваши авторские права? Сообщите нам.
Вуз:
Предмет:
Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_5626_Библиотеки_им_академика_М_И_Перельмана.pdf
6.6 Analytical Techniques in the Detection and Evaluation of Adulterants 111
can be linked to specific pharmacological or biological
activities [69]. The resulting pattern can also serve as a
benchmark for evaluating individual material or formulation tasks. Chromatographic methods, such as HPLC and
TLC are typically used to generate chemical fingerprints,
although other techniques like MS, molecular spectroscopy, capillary electrophoresis, and DNA-based methods
can also be employed for similar purposes [70]. The purpose of this evaluation was to determine how different fingerprinting techniques might be used to standardize and
control the quality of herbal medications. If quality markers have not yet been discovered, then a combination of
fingerprinting and chemometrics is the recommended
way for evaluating the quality of herbal medications.
Chemical profiles and fingerprints from herbal medications can be obtained by instrumental techniques, such as
LC-MS/MS and 1H-NMR spectroscopy. These approaches
show both similarities and differences in the contents of
the pharmaceuticals [71]. These similarities and differences can then be used to categorize samples as authentic
or adulterated herbal drugs. However, since there are
many unknown chemical responses from components in
any herbal drug, this can make data handling difficult. As
a result, powerful statistical techniques called chemometrics are frequently used to process this large chemical
data. Even in cases where the typical chemical ingredients
are not present in exactly the same amounts, the combination of chemical fingerprints with chemometrics enables
accurate sample identification [72].
6.6 Analytical Techniques in the Detection and Evaluation of Adulterants
Ensuring the safety and effectiveness of herbal and natural
therapeutic items is contingent upon their quality and
authenticity. Analytical techniques are essential for identifying adulterants and assessing the quality of crude pharmaceuticals derived from natural sources. Adulteration
and contamination of herbal products are prevalent concerns. Here, we examine some of the most important analytical methods used to achieve this goal:
6.6.1 Microscopy
Microscopic analysis entails analyzing the morphological
and physical properties of plant material. This technique
can be used to identify adulterants and assess the quality of
crude medicines. Microscopists are able to identify differences and abnormalities by contrasting the observed features with reference standards.
Ginseng is a much-desired medicinal herb that comes in
a variety of species and forms. One typical problem is adulteration with other plant components. In this case study,
adulterants in Korean ginseng products were found using a
combination of microscopy and polymerase chain reaction-restriction fragment length polymorphism (PCRRFLP) research. The presence of foreign plant materials in
ginseng samples was visually identified using microscopy,
and the plant species identity was verified by PCR-RFLP
analysis. According to the study, microscopy can be used as
a quick and affordable first screening technique, and PCRRFLP can be used to get confirmation results. This method
showed how well microscopy works to identify adulterants
in ginseng products and emphasized how crucial it is to use
supplementary techniques for thorough QC in the herbal
medicine sector [73].
6.6.2 Chromatographic Techniques
Because it can identify multiple drug components in a sample at once and has a high separation capacity using a complicated combination, the chromatographic approach is
still widely used for the detection of counterfeit pharmaceuticals. Many chromatography methods, including thinlayer, gas, and liquid chromatography, have been used.
Presently, the majority of modern chromatography techniques involve embedding and combining detectors,
including MS, Raman spectroscopy, and other detectors.
6.6.2.1 Thin-layer Chromatography
TLC is a popular and reasonably priced method for detecting and isolating different chemicals in complicated combinations. It is especially useful for determining the identity
of herbal constituents and identifying adulterants through
the comparison of test sample chromatographic profiles
with established standards.
Case Study 1: Identification of Adulterants in Extracts of
Ginkgo biloba
Popular herbal treatment, G. biloba, is well-known for its
possible advantages to the brain and blood vessels.
However, adulteration problems have surfaced because of
its market demand. TLC was utilized in this case study to
identify adulterants in store-bought G. biloba extracts. The
presence of ginkgolic acids (GAs), which are undesired
substances known to trigger allergic reactions, was the primary focus of the researchers’ TLC approach for the qualitative evaluation of G. biloba’s phytochemical profile. The
study effectively illustrated how TLC may be used to detect
adulterants and evaluate the quality of G. biloba products,
emphasizing how important it is to stop the sale of inferior
herbal treatments [74].
112 6 Adulteration and Evaluation of Crude Drugs of Natural Origin
Case Study 2: Authentication of Echinacea Species
Since Echinacea species are thought to have
immunomodulatory qualities, they are frequently employed
in herbal and traditional medicine. But because there are
so many different species of Echinacea on the market,
there are worries about adulteration and misidentification.
TLC in conjunction with desorption electrospray ionization
mass spectrometry (DESI-MS) was employed in this case
study to distinguish between different Echinacea species.
The study showed the effectiveness of TLC and DESIMS in determining the right botanical species and spotting
adulteration, offering a useful tool for guaranteeing the
legitimacy and caliber of Echinacea items on the
market for herbal medicines [75].
6.6.2.2 High-performance Liquid Chromatography
HPLC is an effective method for quantitatively analyzing
the phytochemical components of herbal products. It
makes it possible to identify and measure specific
compounds present in crude medications, which aids
in the detection of adulterants and the calculation of the
amount of active ingredients.
In the field of herbal and natural product analysis,
chromatography is a very adaptable and commonly used
analytical technique. It is essential for both the assessment
of crude medication quality and the identification of
adulterants. Chromatography makes it possible to discover
adulterants and quantify active ingredients by isolating
and characterizing the different chemicals present in
herbal materials. In order to show how effective
chromatography is at assuring the quality and authenticity
of natural medications, we will be discussing its application
in the context of two case studies.
Case Study 1: Chromatographic and Spectral Fingerprints for
the Identification of Adulterated Ginkgo biloba Supplements
The National Institute of Standards and Technology provided
three G. biloba standard reference materials, 12 raw leaf
samples, and 18 commercially available G. biloba
supplements. The fingerprints were collected directly from
UV spectrometry (without the need for chromatography) and
separated using HPLC and a diode array detector. The
regions of the 21 most noticeable chromatographic peaks, the
chromatographic images, and the UV spectral images made
up the fingerprints. Principal component analysis (PCA)
and one-class soft independent modeling of class analogy
were used to analyze the data (SIMCA). It was found
that four of the commercial items included quercetin, one
contained an unidentified flavonol glycoside, and three
contained rutin. Following a MeOH–water extraction,
common chromatographic and spectral patterns were found
for G. biloba supplements that are sold commer
cially. Both genuine and adulterated supplements may be
easily separated from unprocessed leaf components [76].
Case Study 2: Analyzing Green Tea Extracts for Polyphenols
Green tea is well known for the health advantages that polyphenolic chemicals are linked to. Researchers sought to
measure and contrast the number of polyphenols in different green tea extracts in this case study. Green tea extracts
were subjected to analysis of their polyphenolic composition using HPLC. Major polyphenols, such as epicatechin
gallate, epigallocatechin gallate (EGCG), and catechins,
could be quantified thanks to chromatographic separation.
Researchers could guarantee the quality of the product by
identifying changes in the polyphenol concentration by
comparing the chromatograms of several green tea extracts
[77]. An easy, practical, and affordable analytical technique
to evaluate tea authentication is needed. To distinguish and
authenticate tea samples from chicory, a focused HPLC-UV
approach for polyphenolic profiling was presented in this
contribution. This method monitors 17 polyphenolic and
phenolic acids that are commonly found in tea. Based on
the peak regions at three different acquisition wavelengths,
the resulting HPLC-UV polyphenolic profiles were utilized
as sample chemical descriptors in PCA and partial least
squares-discriminant analysis (PLS-DA) investigations [78].
Case Study 3: Alkaloids’ Quantification in Kratom Products
With effects akin to those of an opioid, the plant Kratom
(Mitragyna speciosa) has become increasingly popular as an
herbal remedy. Quantifying the alkaloid concentration is crucial to ensuring both safety and efficacy. The alkaloid content
of different Kratom products was examined using liquid
chromatography-mass spectrometry (LC-MS). Important
alkaloids, such as mitragynine and 7-hydroxymitragynine
may be quantified thanks to chromatographic separation.
Researchers discovered variances in alkaloid concentration
by contrasting the profiles of various goods, which may have
an impact on the potency and safety of the product [79].
Using ultra-performance liquid chromatography-tandem
MS, a method for simultaneously quantifying 10 important
Kratom alkaloids in M. speciosa leaf extracts and commercial
goods. A methodology for quantifying 10 major alkaloids:
mitragynine, speciociliatine, corynoxine, corynoxine B,
corynantheidine, 7-hydroxymitragynine, paynantheine, isocorynantheidine, mitraphylline, and speciogynine was created and verified. Diastereomers or alkaloids sharing the
same ion transitions were separated chromatographically on
an Acquity BEH C18 column with gradient elution using a
mobile phase consisting of acetonitrile and aqueous
ammonium acetate buffer (10 mM, pH 3.5). The new
approach demonstrated linearity for each alkaloid throughout a concentration range of 1–200 ng/mL. Each sample took
6.6 Analytical Techniques in the Detection and Evaluation of Adulterants 113
22.5 minutes to analyze in total. The accuracy, precision, stability, and robustness of the analytical approach were confirmed. The technique was used to quantify kratom alkaloids
in lyophilized teas, ethanolic extracts, alkaloid-rich fractions,
and commercial items following a successful validation
process.
6.6.2.3 Gas Chromatography
Gas chromatography (GC) is an additional technique that
can be used to identify the adulteration of herbal remedies.
It is less expensive, more accurate, sensitive, and repeatable than HPLC, although it is less frequently used than
TLC and liquid chromatography (LC) since it has a volatile
chemical and needs extra pretreatment to attain excellent
thermal stability [30]. The main distinction between the
principles of GC and LC is that, whereas GC employs inert
gases in the same capacity.
As an alternative gas carrier, hydrogen is used in a recent
study by Lin et al. in case there is a future helium scarcity
issue, limited supply, or high cost. Chromatography can
benefit from hydrogen’s speed gains, temperature separations that are lower, longer column life, reduced environmental issues, and enhanced availability. MS is frequently
used as a detector in conjunction with GC. The MS uses a
high-energy electron beam to break up each distinct compound arriving from the GC into ionized fragments, which
are then produced as electrically charged particles or ions
inside the sample molecule. Each charged fragment will
have a distinct mass. The mass-to-charge ratio (m/z) is the
fragment mass divided by its charge. The fragments then
experience acceleration and deflection as they pass through
a brief tunnel and come into contact with a magnetic field.
At the end of the tunnel, they ultimately come into contact
with a detecting plate where the relative abundance and
m/z are computed.
Chromatography methods like HPLC and LC-MS have
shown to be quite useful in identifying adulterants and
assessing natural-source crude pharmaceuticals. We can
see how chromatography techniques enable the separation, identification, and quantification of chemicals within
herbal materials by looking at these case examples.
Through chromatographic profile comparisons with genuine samples, researchers can identify adulterants, measure
active ingredients, and verify the validity and quality of
natural medications. These chromatographic applications
help patients and consumers by enhancing the efficacy and
safety of herbal and natural goods.
Case Study 1: Identification of the Adulteration of the Red
Wines by Isotopic and Chromatographic Methods
The isotopic and chromatographic studies, along with multivariate statistical analysis of the data, were used to evaluate
red wine adulteration. The study makes use of 29 table wine
samples that were bought from the market and placed in
PET bottles. When evaluating the stable isotope content
(δ13C and δ18O), which are known as origin markers, it was
possible to determine the exogenous addition of sugar and
water to the counterfeit table red wines. Additional classical
factors that further supported this were the wines’ alcoholic
strength (vol.) and the use of artificial sweeteners, artificial
red dyes (used to remedy for inadequacies in taste and color),
and 5-(hydroxymethyl)-2-furaldehyde (HMF) [80].
6.6.3 Hyphenated Techniques
6.6.3.1 Gas Chromatography-mass Spectrometry
For the analysis of volatile chemicals in natural products,
GC-MS works well. It is employed to verify the legitimacy
of herbal medications, identify impurities, and validate the
presence of particular chemicals.
The detection of meprobamate, cyamemazine, caffeine,
morphine, diazepam, and citalopram using WB and VH
from humans and rabbits was identified in 2015. The group
reports that whereas all six medications were found and
correlated with WB in rabbits, this was not the case in
human subjects for cyamemazine and diazepam.
Nevertheless, human detections of all six substances were
made. Gas chromatography-tandem mass spectrometry
(GC-MS/MS), which is distinct from traditional GC-MS in
that it adds a second quadrupole inline that is spaced apart
by a collision cell, was interestingly employed by this
group. After entering the collision cell and additional fragmentation, the ions from the first quadrupole proceed to
the second quadrupole in order to be detected [81].
Case Study 1: Authentication of Ginkgo biloba Extract Using
GC-MS
An approach to the quantitative analysis and characterization of GAs in plant materials, extracts, and commercial
products of G. biloba L. is high-resolution GC-MS with a
chosen ion monitor. Popular natural treatment G. biloba is
well-known for improving cognitive function. Nevertheless,
there have been cases of adulteration with other plant species on the market. G. biloba extracts were verified through
the use of GC-MS. A GC-MS technique was employed in
the study to examine the volatile components present in
extracts of G. biloba. The purportedly tampered samples
were contrasted with the real ones. To locate and measure
the adulterants, the mass spectra and chromatographic
profile were examined. An unexpected peak was detected
in the suspected samples by GC-MS analysis. Sophora
japonica was shown to be the adulterant after more
research. The degree of adulteration was verified through
the measurement of particular marker chemicals. This
114 6 Adulteration and Evaluation of Crude Drugs of Natural Origin
case study demonstrates how well GC-MS can identify
minute adulterations in herbal medications [82].
6.6.3.2 Liquid Chromatography-mass Spectrometry
LC-MS is flexible and capable of analyzing a large number
of substances. It is employed in the detection of possible
adulterants as well as the identification of chemical markers and active components in herbal products. Other potential samples that have been the subject of recent publications
include cerumen (earwax); bone; adipocere, sometimes
referred to as corpse wax, grave wax, or mortuary wax;
brain tissue; flies; and pupae.
Case Study 1:
It was found that the detection time window of cerumen,
or earwax, was longer than that of urine but shorter than
that of hair. Their findings showed that tests on the corresponding cerumen samples produced positive findings for
all drugs used recently, including methadone, opioids,
cocaine, amphetamine and its derivatives, and diazepam.
In situations when drugs were only detected in the urine,
cerumen samples were also discovered to be positive.
Nevertheless, only 52.5% of the patients under investigation had drug levels in the cerumen when only the hair
tested positive.[83].
Case Study 2: Authenticity of Ginkgo biloba L. Plant Materials
and Dried Leaf Extracts
A non-targeted method using chemometrics and liquid chromatography-high resolution mass spectrometry (LC-HRMS)
to ascertain the legitimacy of dried leaf extracts and plant
materials of G. biloba L. Due to economic factors, such as rising market demand, high production and raw material costs,
and other factors, the practice of adulterating G. biloba L.
plants and extracts is spreading. For the supplements to be
effective, QC must be strengthened to prevent adulterations.
As an unsupervised exploratory technique, PCA and liquid
chromatography-high resolution mass spectrometry
(LC-HRMS) were used in this investigation to analyze, identify, and evaluate the contaminated G. biloba L. plant materials and dried leaf extracts. After obtaining PCA loadings and
scores, compound identification was applied [84].
6.6.4 Spectroscopic Methods
6.6.4.1 Nuclear Magnetic Resonance Spectroscopy
NMR spectroscopy is another tool that can be used to detect
adulteration of herbal products. NMR spectroscopy is an
analytical technique that can be used to determine the
molecular structure, composition, and purity of a material
by utilizing the magnetic properties of particular nuclei.
The basic principle of NMR is that some nuclei can only
exist in specific nuclear spin states when there is an external
magnetic field present. NMR uses a big magnet to study the
intrinsic spin properties of atomic nuclei. NMR uses radiofrequency waves, a form of electromagnetic radiation, to
stimulate transitions between nuclear energy levels, just
like all other spectroscopies (resonance) [85]. A study that
utilized low-field (LF) 1H NMR spectra, a newly developed
NMR technique, to examine sibutramine and phenolphthalein found in diet supplements intended to promote weight
loss. An innovative method based on the application of a
new generation of compact NMR is called LF NMR. It offers
a chance to use non-deuterated solvents in favor of more
expensive or harmful techniques. This procedure yielded
the lowest limit value of 3 mg/100 mg. This score indicates
that while it is thought to be a sensitive method, it is not as
sensitive as other spectroscopic methods [86].
Case Study 1: Adulterant Detection in Soybean Oil
The botanical source of edible oils has been associated with
health benefits, especially those mediated by fatty acids
like omega 3 and omega 9. Brazil nut, chia, linseed, sesame
(raw and toasted), and soybean oils are evaluated utilizing
1
chemometrics and
H NMR to examine the fatty acid profiles. PCA plots for reference and commercial samples
showed significant correlations between chemical composition and botanical provenance. Strong evidence of adulteration of commercial Brazil nut oil was proven through
the use of a spiking method. Our study shows that NMR
and chemometrics may properly connect the fatty acid profile and botanical origin, which makes them valuable for
detecting sample adulteration [87].
6.6.4.2 Mass Spectrometry
Mass spectrometry (MS) is an analytical technique used to
calculate an ion’s mass-to-charge ratio (MS). The results
are typically shown using a mass spectrum, which is a plot
of intensity as a function of mass-to-charge ratio [28].
When compared to alternative techniques, MS has a greater
variety of substances it can identify.
Case Study 1: Detection of Adulterants in Herbal Ingredients
Using wooden-tip electrospray ionization MS (WT-ESI-MS),
to analyze over five medicines that were not disclosed (doxepin, zopiclone, diazepam, nitrazepam, clonazepam, melatonin, zaleplon, chlorpheniramine, alprazolam, and
chlordiazepoxide) from a nutritional supplement that contained herbal ingredients. One method that could be utilized for the direct examination of raw materials is
WT-ESI-MS. For ionization and sampling, this method
makes use of inexpensive, easily accessible wooden toothpicks, which can be used directly with nano-ESI ion sources
that are sold commercially. The approach can be applied to
References 115
the analysis of samples in different forms, and the firm,
slender hardwood tips make sampling exceedingly easy.
The LOD values obtained with this approach were 0.1 mg/g,
indicating an excellent sensitivity analytical procedure [88].
6.7 Challenges in Detection of Adulterants
Because of the intrinsic complexity of these botanical matrices, the identification of adulterants in natural crude medicines presents a variety of challenging issues. For example,
several phytochemicals are present in herbal remedies,
making it difficult to distinguish between naturally occurring substances and possible adulterants. A further degree
of complexity is introduced by the variety of plant sources,
which is impacted by climate, geography, soil properties,
and harvesting techniques. This makes it difficult to build
reliable baseline profiles for comparison. The problem of
detecting undeclared substances, including synthetic chemicals or other botanicals not mentioned on product labels, is
difficult to overcome [89]. Microbiological contamination,
which is frequently undetectable, can jeopardize the purity
and safety of natural crude medications. Sample preparation becomes important yet difficult, requiring exact extraction methods that do not compromise sensitivity or produce
artifacts. For analytical methods to reliably identify traces of
adulterants, they must have a high sensitivity. Developing
universal detection protocols is made more difficult by the
absence of defined techniques for evaluating natural crude
medicines. It is essential to verify the botanical identity of
herbal goods because it is possible for inaccurate plant species identification to result in the unintentional addition of
adulterants. Differentiating natural crude pharmaceuticals
can be challenging due to their chemical complexity, as
many of the molecules have identical structures. Regional
differences in laws and regulations exacerbate the problem
since different requirements for herbal products make it difficult to develop global recommendations for adulterant
detection [90]. To tackle these obstacles, researchers and
regulatory agencies must work together, employ cuttingedge analytical techniques, and develop standardized QC
procedures for the herbal products sector [20].
because of things like lack of regulatory supervision, erratic
environmental conditions, and financial incentives. It calls
attention to the urgent need for standardized testing procedures and QC measures while endangering the efficacy
and safety of herbal products. The development of
advanced techniques like chromatography, spectroscopy,
and DNA barcoding is attracting the attention of researchers and regulatory agencies due to its ability to properly
detect adulterants and authenticate herbal ingredients.
The enormous range of plant species utilized in traditional
medicine, the requirement for worldwide standards to be
harmonized, and the preservation of traditional knowledge
while maintaining consumer safety are some of the challenges faced in this field. The task of integrating traditional
herbal remedies with contemporary scientific instruments
is challenging but essential. Significant barriers may
include poor QC, a lack of research funding, and regional
differences in regulatory regimes.
The future of evaluating herbal drugs and preventing
adulteration is multidisciplinary cooperation. In addition to
embracing cutting-edge technology like MS, nuclear magnetic resonance, and artificial intelligence, research activities should continue to hone and validate analytical
methodologies. Product quality will be improved through
the standardization of herbal materials, which includes the
creation of databases, reference standards, and monographs. To maintain uniformity and safety, it is imperative
that rules and standards for herbal medications be harmonized globally. Furthermore, it is critical to inform consumers, industry stakeholders, and practitioners of traditional
medicine about the dangers of adulteration and the value of
QC. Risks of adulteration can be decreased by growing
medicinal plants under regulated conditions or using sustainable farming methods. Moreover, enhanced traceability
and transparency across the supply chain might discourage
dishonest behavior. In conclusion, academics, regulators,
and industry actors all have a shared obligation to address
the issues of adulteration and the assessment of crude pharmaceuticals derived from natural sources. The field of
herbal medicine may continue to develop, offering safe and
efficient natural therapies for a wide range of health issues
while protecting traditional knowledge and biodiversity, by
utilizing cutting-edge technologies and promoting international cooperation.
6.8 Conclusion and Future Perspectives
In the fields of pharmacology and herbal medicine, the
adulteration and assessment of crude pharmaceuticals
derived from natural sources pose significant prospects as
well as obstacles. Adulteration is still a problem today
References
1 Nisar, B., Sultan, A., Rubab, S.L. (2018). Comparison of
medicinally important natural products versus synthetic
drugs – a short commentary. Natural Products Chemistry &
Research 6 (2): 308.
116 6 Adulteration and Evaluation of Crude Drugs of Natural Origin
2 Pom, B. (2020). Lindungi Masyarakat dari Obat
Tradisional, Suplemen Kesehatan, dan Kosmetik yang
Berisiko terhadap Kesehatan. Badan POM.
3 Minh, D.T.C., Huyen, N.T.T., Anh, N.T.K., et al. (2019).
Detection of sildenafil adulterated in herbal products
using thin layer chromatography combined with surface
enhanced Raman spectroscopy: “Double coffee-ring
effect” based enhancement. Journal of Pharmaceutical
and Biomedical Analysis 174: 340–47.
4 Ansari, S. (2021). Overview of traditional systems of
medicine in different continents. Preparation of
Phytopharmaceuticals for the Management of Disorders,
431–73. Amsterdam: Elsevier.
5 Zhou, X., Li, C-G., Chang, D., et al. (2019). Current
status and major challenges to the safety and efficacy
presented by Chinese herbal medicine. Medicines
6 (1): 14.
6 Pratiwi, R., Dipadharma, R.H.F., Prayugo, I.J., et al.
(2021). Recent analytical method for detection of
chemical adulterants in herbal medicine. Molecules 26
(21): 6606.
7 Shaheen, S., Ramzan, S., Khan, F., et al. (2019).
Adulteration in herbal drugs: A burning issue. USA:
Springer.
8 Agarwal, P. and Goyal, A. (2021). A comprehensive
review on adulteration and substitution of crude drugs.
Asian Journal of Pharmaceutical and Clinical Research
14 (4): 33–8.
9 Gorham, J.R. (1981). Principles of Food Analysis for
Filth, Decomposition, and Foreign Matter. US
Department of Health and Human Services, Public
Health Service, Food and Drug Administration.
10 Jha, S.N. (2015). Rapid Detection of Food Adulterants
and Contaminants: Theory and Practice. Academic
Press.
11 Masullo, M., Montoro, P., Mari, A., et al. (2015).
Medicinal plants in the treatment of women’s disorders:
Analytical strategies to assure quality, safety and
efficacy. Journal of Pharmaceutical and Biomedical
Analysis 113: 189–211.
12 Kneifel, W., Czech, E. and Kopp, B. (2002). Microbial
contamination of medicinal plants-a review. Planta
Medica 68 (01): 5–15.
13 Tropea, A. (2022). Microbial contamination and public
health: an overview. International Journal of
Environmental Research and Public Health 19 (12): 7441.
14 Navale, V., Vamkudoth, K.R., Ajmera, S., et al. (2021).
Aspergillus derived mycotoxins in food and the
environment: prevalence, detection, and toxicity.
Toxicology Reports 8: 1008–30.
15 Gage, D. (1996). Aloe vera: Nature’s Soothing Healer.
USA: Inner Traditions/Bear & Co; 1996.
16 Calahan, J., Howard, D., Almalki, A.J., et al. (2016).
Chemical adulterants in herbal medicinal products: a
review. Planta Medica 82 (6): 505–15.
17 Momtaz, M., Bubli, S.Y., and Khan, M.S. (2023).
Mechanisms and health aspects of food adulteration: a
comprehensive review. Foods; 12 (1): 199.
18 Puneshwar, K. (2021). Controversy, adulteration and
substitution: burning problems in ayurveda practices. In
(ed: Hany AE-S) Natural Medicinal Plants. Rijeka:
IntechOpen.
19 Mortas, M., Awad, N., and Ayvaz H. (2022). Adulteration
detection technologies used for halal/kosher food
products: an overview. Discover Food 2 (1): 15.
20 Choudhary, A., Gupta, N., Hameed, F., et al. (2020). An
overview of food adulteration: Concept, sources, impact,
challenges and detection. International Journal of
Chemical Studies 8 (1): 2564–73.
21 Soon, J.M. (2022). Food fraud countermeasures and
consumers: A future agenda. In: (ed: Bhat, R.) Future
Foods, 597–611. Academic Press.
22 Posadzki, P., Watson, L., and Ernst, E. (2013).
Contamination and adulteration of herbal medicinal
products (HMPs): an overview of systematic reviews.
European Journal of Clinical Pharmacology 69: 295–307.
23 Ernst, E. (2004). Risks of herbal medicinal products.
Pharmacoepidemiology and Drug Safety 13 (11): 767–71.
24 Zhang, J., Wider, B., Shang, H., et al. (2012). Quality of
herbal medicines: challenges and solutions.
Complementary Therapies in Medicine 20 (1–2): 100–06.
25 Lynch, E. and Braithwaite, R. (2005). A review of the
clinical and toxicological aspects of ‘traditional’(herbal)
medicines adulterated with heavy metals. Expert
Opinion on Drug Safety 4 (4): 769–78.
26 Biswas, J.K., Rai, M., Mondal, M., et al. (2018) The
flop side of using heavy metal(oids)s in the traditional
medicine: toxic insults and injury to human health.
In: Rai, M., Ingle, A.P., Medici, S.) Biomedical
Applications of Metals, 257–76. Cham: Springer
International Publishing.
27 Kumar, G. and Gupta, Y.K. (2012). Evidence for safety of
Ayurvedic herbal, herbo-metallic and Bhasma
preparations on neurobehavioral activity and oxidative
stress in rats. An International Quarterly Journal of
Research in Ayurveda 33 (4): 569–75.
28 Street, R.A. (2012). Heavy metals in medicinal plant
products – An African perspective. South African
Journal of Botany 82: 67–74.
29 Cowell, W., Ireland, T., Vorhees, D., et al. (2017). Ground
turmeric as a source of lead exposure in the United
States. Public Health Reports 132 (3): 289–93.
30 Shekhar, N.R. and Nagappan, K. (2022). Herbal drug
adulteration with synthetic phytoconstituents and their
References 117
analogs as adulterants a conundrum in quality control
of herbal formulations: a review. Annals of Forest
Research 65 (1): 537–53.
31 Alkassab, A.T., Thorbahn, D., Frommberger, M., et al.
(2020). Effect of contamination and adulteration of wax
foundations on the brood development of honeybees.
Apidologie 51 (4): 642–51.
32 Salgueiro, L., Martins, A. and Correia, H. (2010). Raw
materials: the importance of quality and safety. A
review. Flavour and Fragrance Journal. 25 (5): 253–71.
33 Alamgir, A. and Alamgir, A. Herbal drugs: their
collection, preservation, and preparation; evaluation,
quality control, and standardization of herbal drugs. In:
Therapeutic Use of Medicinal Plants and Their Extracts,
453–95 Volume 1: Pharmacognosy. Springer.
34 Ahmed, S. and Hasan, M.M. (2015). Crude drug
adulteration: a concise review. World Journal of
Pharmacy and Pharmaceutical Sciences 4 (10): 274–83.
35 More, D. and Giradkar, P.S. (2020). Herbal drug
adulteration: a Hindrance to the development of
ayurveda medicine. International Journal of Ayurvedic
and Herbal Medicine 10 (2): 3764–770.
36 Sharma, V. and Rao, L.J.M. (2014). An overview on
chemical composition, bioactivity and processing of
leaves of Cinnamomum tamala. Critical Reviews in Food
Science and Nutrition 54 (4): 433–48.
37 Vijayambika, C., Jegadeesan, M., and Ganthi, S. (2011).
Comparative anatomical studies on seeds of Mucuna
Adans. and Canavalia Dc. species. Indian Journal of
Natural Products and Resources 2 (1): 81–7.
38 Ahmed, S.N., Ahmad, M., Zafar, M., et al. (2019).
Comparative light and scanning electron microscopy in
authentication of adulterated traded medicinal plants.
Microscopy Research and Technique 82 (7): 1174–1183.
39 Jose, A., Leela, N.K., Zachariah, T.J., et al. (1970).
Evaluation of coumarin content and essential oil
constituents in Cinnamomum cassia (Nees & T. Nees)
J. Presl. Journal of Spices and Aromatic Crops 43–51.
40 Roy, A., Mallick, A., and Kaur, A., et al. (2013).
Adulteration and Substitution in Indian Medicinal
Plants. Medicine, Environmental Science.
41 Dubey, R. and Sawant, B.S. (2015). Current scenario of
adulterants and substitutes of medicinal plants: a
review. Journal of Pharmaceutical and Scientific
Innovation.
42 Prakash, O., Jyoti, A.K., Kumar, A., et al. (2013).
Adulteration and substitution in Indian medicinal
plants: an overview. Journal of Medicinal Plants Studies
1 (4): 127–132.
43 Sultana, S., Ahmad, M., Zafar, M., et al. (2012).
Authentication of herbal drug Senna (Cassia
angustifolia Vahl.): A village pharmacy for Indo-Pak
Subcontinent. African Journal of Pharmacy and
Pharmacology 6 (30): 2299–2308.
44 Jahromi, M., Zarshenas, M.M., and Rizvandi, N. (2022).
Assessment of authenticity of market samples of
hypericum using phytochemical fingerprinting tools.
European Journal of Medicinal Plants 2022:1–13.
45 Sahoo, N., Manchikanti, P., and Dey, S. (2010). Herbal
drugs: standards and regulation. Fitoterapia 81 (6): 462–471.
46 Joharchi, M.R. and Amiri M.S. (2012). Taxonomic
evaluation of misidentification of crude herbal drugs
marketed in Iran. Avicenna Journal of Phytomedicine 2
(2): 105–12.
47 Ahmad, I., Ahmad Khan, M.S., and Cameotra, S.S.
Quality assessment of herbal drugs and medicinal plant
products. Encyclopedia of Analytical Chemistry 46: 1–17.
48 Kumar, S. (2014). Adulteration and substitution in
endangered ASU medicinal plants of India: a review.
International Journal of Medicinal and Aromatic
Plants;4: 56–73.
49 Thakur VV, Tiwari S, Tripathi N, et al. (2019). Molecular
identification of medicinal plants with amplicon length
polymorphism using universal DNA barcodes of the
atpF-atpH, trnL and trnH-psbA regions. 3 Biotech. 9 (5):
188.
50 Sasikumar B, Swetha V, Parvathy V, et al. (2016).
Advances in adulteration and authenticity testing of
herbs and spices. In: Advances in Food Authenticity
Testing 585–24. Elsevier.
51 Bennett, B.C., and Balick, M.J. (2008). Phytomedicine
101: plant taxonomy for preclinical and clinical
medicinal plant researchers. Journal of the Society for
Integrative Oncology 6 (4): 150–57.
52 Zafar, M., Ahmad, M., Sultana, S., et al. (2019). Micro‐
morphological, environmental and phytochemical
investigation of herbal medicines by using LM and
SEM: a quality control tool. Microscopy Research and
Technique 82 (5): 550–57.
53 Ahmed, S.N., Ahmad, M., Yaseen, G., et al. (2021).
Quality assurance and authentication of herbal drug
(Argyrolobium roseum and Viola stocksii) through
comparative light and scanning electron microscopy.
Microscopy Research and Technique 284 (1): 28–37.
54 Muyumba, N., Mutombo, S., Sheridan, H., et al. (2021).
Quality control of herbal drugs and preparations: The
methods of analysis, their relevance and applications.
Talanta Open 4: 100070.
55 Osman, A.G., Raman, V., Haider, S., et al. (2019).
Overview of analytical tools for the identification of
adulterants in commonly traded herbs and spices.
Journal of AOAC International 102 (2): 376–85.
56 Dattatreya, A.M., Nanjegowda, D.K., and Viswanath, P.
(2011). Microscopic detection of adulteration of Bengal
118 6 Adulteration and Evaluation of Crude Drugs of Natural Origin
gram (Cicer arietinum) flour with other legume flour
based on the seed testa macrosclereids. Journal of Food
Science and Technology 48 (1): 114–19.
57 Siegel, S.M. The Plant Cell Wall: A Topical Study of
Architecture, Dynamics, Comparative Chemistry and
Technology in A Biological System. Pergamon.
58 Patil, D.N., Keshamma, E., Prathibha, K., et al. (2022).
Pharmacognosy: A Science of Natural Products. Book
Saga Publications.
59 Ichim, M.C., Häser, A., and Nick, P. (2020). Microscopic
authentication of commercial herbal products in the
globalized market: potential and limitations. Frontiers in
Pharmacology 11: 876.
60 Tambare, P., Tamboli, F.A., and More, H.N. (2011).
Standardization of herbal drugs: an overview.
International Journal of Pharmacognosy and
Pharmaceutical Sciences 2 (12): 56–60.
61 Kunle, O.F., Oluyemisi, F., Egharevba, H.O., et al.
(2012). Standardization of herbal medicines-A review.
International Journal of Biodiversity and Conservation 4
(3): 101–12.
62 Nehal, N., Choudhary, B., Nagpure, A., et al. (2021).
DNA barcoding: a modern age tool for detection of
adulteration in food. Critical Reviews in Biotechnology 41
(5): 767–91.
63 Klein-Junior, L.C., de Souza, M.R., Viaene, J., et al.
(2021). Quality control of herbal medicines: From
traditional techniques to state-of-the-art approaches.
Planta Medica 87 (12/13) : 964–88.
64 Ganie, S.H., Upadhyay, P., Das, S., et al. (2015).
Authentication of medicinal plants by DNA markers.
Plant Gene 4: 83–99.
65 Chester, K., Tamboli, E., Paliwal, S., et al. (2016).
Significance of molecular markers in pharmacognosy: a
modern tool for authentication of herbal drugs. Drug
Development and Therapeutics 7 (2): 96.
66 Patel HK, Fougat RS, Kumar S, et al. (2015). Detection
of genetic variation in Ocimum species using RAPD and
ISSR markers. 3 Biotech 5 (5): 697–707.
67 Sitthithaworn, W., Vimolmangkang, S., Chittasupho, C.,
et al. (2009). Pharmacognostic investigation of the
leaves of Mentha cordifoliaand its DNA fingerprints.
Thai Pharmaceutical and Health Science Journal 4 (1):
9–14.
68 Devaiah, K., Balasubramani, S.P., and
Venkatasubramanian, P. (2011). Development of
randomly amplified polymorphic dna based scar marker
for identification of Ipomoea mauritiana Jacq
(Convolvulaceae). Evidence-Based Complementary and
Alternative Medicine 2011 (1): 868720.
69 Mohammed Abubakar, B., Mohd Salleh, F., Shamsir
Omar, M.S., et al. (2017). Review: DNA barcoding and
chromatography fingerprints for the authentication of
botanicals in herbal medicinal products. Evidence-Based
Complementary and Alternative Medicine 2017 (1):
1352948.
70 Xu, L., Han, X., Qi, Y., et al. (2009). Multiple compounds
determination and fingerprint analysis of Lidanpaishi
tablet and keli by high-performance liquid
chromatography. Analytica Chimica Acta 633 (1):
136–48.
71 Bārzdiņa, A., Paulausks, A., Bandere, D., et al. (2022).
The potential use of herbal fingerprints by means of
HPLC and TLC for characterization and identification
of herbal extracts and the distinction of latvian native
medicinal plants. Molecules 27 (8): 2555.
72 Noviana, E., Indrayanto, G., and Rohman, A. (2022).
Advances in fingerprint analysis for standardization and
quality control of herbal medicines. Frontiers in
Pharmacology 13: 853023.
73 Diao, Y., Lin, X.M., Liao, C.L., et al. (2009).
Authentication of Panax ginseng from its adulterants by
PCR-RFLP and ARMS. Planta Medica 75 (5): 557–60.
74 Sticher, O., Meier, B., and Hasler, A. The analysis of
Ginkgo flavonoids. Ginkgo biloba, 228–56. CRC Press.
75 Cheng, S.-C., Bhat, S., Lee, C.-W., et al. (2018). Thin
layer chromatography combined with electrospray
ionization mass spectrometry for characterizing herbal
compounds. International Journal of Mass Spectrometry
434: 264–271.
76 Liu, X.-G., Wu, S.-Q., Li, P., et al. (2015). Advancement
in the chemical analysis and quality control of flavonoid
in Ginkgo biloba. Journal of Pharmaceutical and
Biomedical Analysis 113: 212–25.
77 Reich, E., Schibli, A., Widmer, V., et al. (2006). HPTLC
methods for identification of green tea and green tea
extract. Journal of Liquid Chromatography & Related
Technologies 29 (14): 2141–51.
78 Romers, T., Saurina, J., Sentellas, S., et al. (2023).
Targeted HPLC-UV polyphenolic profiling to detect and
quantify adulterated tea samples by chemometrics.
Foods 12 (7): 1501.
79 Manwill, P.K., Flores-Bocanegra, L., Khin, M., et al.
(2022). Kratom (Mitragyna speciosa) validation:
quantitative analysis of indole and oxindole alkaloids
reveals chemotypes of plants and products. Planta
Medica 88 (9–10): 838–57.
80 Geana, E.I., Popescu, R., Costinel, D., et al. (2016).
Verifying the red wines adulteration through isotopic
and chromatographic investigations coupled with
multivariate statistic interpretation of the data. Food
Control 62: 1–9.
81 Bévalot, F., Cartiser, N., Bottinelli, C., et al. (2015).
Correlation of bile and vitreous humor concentrations
References 119
with blood drug concentrations for forensic
interpretation: a comparative study between animal
experimental and human postmortem data. Forensic
Toxicology 33: 131–40.
82 Wang, M., Zhao, J., Avula, B., et al. (2014). High-
resolution gas chromatography/mass spectrometry
method for characterization and quantitative analysis of
ginkgolic acids in Ginkgo biloba plants, extracts, and
dietary supplements. Journal of Agricultural and Food
Chemistry 62(50): 12103–111.
83 Onchoi C, Kongtip P, Nankongnab N, et al. (2020).
Organophosphates in meconium of newborn babies
whose mothers resided in agricultural areas of Thailand.
The Southeast Asian Journal Of Tropical Medicine and
Public Health 51 (1): 77.
84 Cruz, M.B., Place, B.J., Wood, L.J., et al. (2020). A
nontargeted approach to determine the authenticity of
Ginkgo biloba L. plant materials and dried leaf extracts
by liquid chromatography-high-resolution mass
spectrometry (LC-HRMS) and chemometrics. Analytical
and Bioanalytical Chemistry 412 (25): 6969–82.
85 Miao, L., Liu, Y., Li, H., et al. (2017). Two-dimensional
correlation infrared spectroscopy applied to the
identification of ephedrine and pseudoephedrine in
illegally adulterated slimming herbal products. Drug
Testing and Analysis 9 (2): 221–29.
86 Wu, N., Balayssac, S., Danoun, S., et al. (2020).
Chemometric analysis of low-field (1)h nmr spectra for
unveiling adulteration of slimming dietary supplements
by pharmaceutical compounds. Molecules 25 (5): 1193.
87 Ravaglia, L.M., Pizzotti, A.B.C., and Alcantara, G.B.
(2019). NMR-based and chemometric approaches
applicable to adulteration studies for assessment of the
botanical origin of edible oils. Journal of Food Science
and Technology 56 (1): 507–11.
88 Hu, B., Huang, Y., Yin, G., et al. (2016). Rapid detection
of adulterated drugs in herbal dietary supplements by
wooden-tip electrospray ionization mass spectrometry.
Analytical Methods 8 (38): 6840–46.
89 Se, K.W., Wahab, R.A., Syed Yaacob, S.N., et al. (2019).
Detection techniques for adulterants in honey:
Challenges and recent trends. Journal of Food
Composition and Analysis 80: 16–32.
90 McGrath, T.F., Haughey, S.A., Patterson, J., et al. (2018).
What are the scientific challenges in moving from
targeted to non-targeted methods for food fraud testing
and how can they be addressed? Spectroscopy case
study. Trends in Food Science & Technology 76: 38–55.
