heavy metal analysis in herbal formulation by akshay kakde
TRANSCRIPT
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“ Heavy Metal Analysis In Herbal and Ayurvedic Formulation”
Presented By - Mr. Akshay G. Kakde
M. Pharm IIIrd Sem
Guided By - Dr. S. S. Bhujbal
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Dr. D. Y. Patil Institute Of Pharmaceuticals Sciences and Research
Pimpri,411018
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Contents
• Introduction
• Heavy metals
• Classification of contaminant and residue in herbal medicine
• Limits
• Need for Heavy Metal Analysis
• Detection method
• Herbal formulations
• Solution for avoiding heavy metals
• Conclusion
• References
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Introduction
• Ayurvedic medicine is a system of healing that originated in
ancient India.
In sanskrit
Ayur – Life or Living
Veda – Knowledge
So, Ayurveda has been defined as the “Knowledge of living”
or the “Science of longevity”.
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• Ayurveda consist of various dosage form such as Bhasma, Churna,
Vatika, Lepa, Arka, Rasa-yoga etc.
• Several Ayurvedic medicines readily available are found to contain
steroids and heavy metals ,both are harmful to the human body if
taken in excess.
• Heavy metal are found in herbal medicine, herbal drugs and
formulation.
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Heavy Metal
• Heavy metals are generally defined as metals with relatively
high density (5 g/cm3), atomic weights, or atomic numbers.
• Heavy metals are toxic to human health??
• Heavy metals are largely found in nature as minerals and ore.
• To a small extent they enter our bodies via food, drinking
water, air and herbal medicines.
• Most common heavy metals are lead(Pb), mercury(Hg),
cadmium(Cd), Chromium (Cr) and arsenic(As).
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HEAVY METAL TOXICITY CONCERNS
• Prolong exposure to heavy metals may cause adverse health effect and
toxicity due to the capability of heavy metals to bio accumulate and
disrupt the functions of vital organs in the human body such as brain,
kidneys and liver.
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! SORRY! BUT IT’S NOT TRUE !
• This observation is unacceptable to many Ayurvedic physicians
• Their contention is that so called heavy metals are not heavy on
the human body and that Ayurvedic medicines containing
Heavy metals (used in the form of bhasmas) are completely safe to
use.
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•Herbal Compositions
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Herbal / Ayurvedic
Product / Dosage
Form
Therapeutic use Compositions Found
Rajata Bhasma Diabetes, fever in T.B. Calcined Silver Particles
lime juice
Aarogyavardhini Vati Heart disease, Stomach
disease
Mercury
Karela Tablet Supports normal sugar
level
Lead
Maha Sudarshan Churna Used in fever Mercury , Lead
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Properties of Heavy metal
• They occur near the bottom of the periodic table
• Have high densities
• Toxic in nature
• Non-biodegradable
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Sources of Heavy Metal
• Most commonly sources are
Soil
Water
Air
Pesticides
Manufacturing Process
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Classification of contaminant and residue in Herbal medicine as per WHO
Class Group Subgroup Sp.
Example
Possible
source
Chemical
contaminants
Toxic and
hazardous
materials
Toxic metals
and non-
metals
Lead,
cadmium,
mercury,
chromium
arsenic, nitrite
Polluted soil
and water,
during
cultivation/
growth,
manufacturin
g process
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CONTAMINANTS
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Cont..
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RESIDUE
Class Group Subgroup Sp. Example Possible
source
Agrochemical
residues
Pesticides Insecticides Carbamate,
chlorinated
hydrocarbons,
organophosph
orus
Air, soil,
water, during
cultivation/gro
wth,
postharvest
processing
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Limit for Heavy Metal in medicinal products as per WHO,2005
Arsenic
(As)
Lead (Pb) Cadmium
(Cd)
Chromium
(Cr)
Mercury
(Hg)
India 3 ppm 10 ppm 0.3 ppm 1 ppm
China 2 ppm 10 ppm 1 ppm - 0.5 ppm
Singapore 5 ppm 20 ppm 0.5 ppm
Thailand 4 ppm 10 ppm 0.3 ppm - -
Canada 5 ppm 10 ppm 0.3 ppm 2 ppm 0.2 ppm
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Countries Heavy metal
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Side effect of Heavy MetalsMetal Acute Chronic
Arsenic Nausea, vomiting,
diarrhoea, encephalopathy,
painful neuropathy
cancer: lung, bladder, skin,
encephalopathy
Lead Nausea, vomiting, encephalopathy
(headache, seizures)
Encephalopathy, anemia,
abdominal pain, nephropathy, foot-
drop/ wrist-drop
Cadmium Pneumonitis Proteinuria, lung cancer,
osteomalacia
Chromium GI haemorrhage, haemolysis, acute
renal failure
Pulmonary fibrosis, lung cancer
(inhalation)
Mercury Elemental (inhaled): fever, vomiting,
diarrhoea,
Inorganic salts (ingestion): caustic
gastroenteritis
Nausea, nephrotic syndrome;
hypersensitivity (Pink disease)
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Need for Heavy Metal Analysis ??.
• To determine the concentration of heavy metal in herbal
formulation as per standard regulatory guidelines.
• To determine the purity of formulation.
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Detection method
•Common method
1. Limit tests
2. Flame photometry Method
•Advanced method
1. X-Ray Diffraction Method
2. X-Ray Fluorescence Spectrometer Method
3. Atomic Absorption Spectroscopy method
4. Inductively Coupled Plasma-Mass Spectroscopy Method
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Common Method
•Limit Test-
1. Common Limit test for all Heavy Metal
2. Limit test for Arsenic
3. Limit test for Lead
4. Limit test for Cadmium
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Cont…
1.Common Limit test for Heavy Metal
-Using Dilute Acetic acid
2. Limit test for Arsenic
-Using Ammonium Oxalate
3. Limit test for Lead
-Using Ammonia cyanide solution
4. Limit test for Cadmium
-Using oxalic acid
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2. Flame photometry Method
A photoelectric flame photometer is a device used in inorganicchemical analysis to determine the concentration of certain metal ions,among them sodium(Na), Potassium(K), lithium(Li), and calcium(Ca).
Group 1 and Group 2 metals are quite sensitive to Flame Photometry due to their low excitation energies.
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•Applications
It is used in determination of potassium(K), sodium(Na),
magnesium(Mg) and calcium(Ca) in biological fluids like serum,
plasma, urine.
It used in soil analysis.
Aluminum(Al), Barium(Br), Calcium(Ca), Chromium(Cr),
Copper(Cu), Iron(Fe), lead(Pb), Magnesium(Mg), Potassium(K),
zinc(Zn) and strontium(Sr) in formulation and product.
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Advance method For Analysis
1. X-Ray Diffraction Method (XRD)It is common technique for the study of crystal structures and atomic spacing. X-ray
diffraction is based on constructive interference of monochromatic X-rays and a crystallinesample.
A B C
X-RD X-ray angle Sample and Graph 21
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•Working of XRD Instrument
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• X-Ray Diffractogram of Nanocrystalline Nature of Lead in Naga Bhasma
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•Applications
Characterization of crystalline materials.
Determination of unit cell dimensions.
Measurement of sample purity.
Determining the thickness, roughness and density of crystals.
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2. X-Ray Fluorescence Spectrometer Method (XRF)
XRF is based on the principle that individual atoms, when excited by an external
energy source, emit their own characteristic fluorescence X-ray.
Fig –Shimadzu XRF-EDX-720
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•Working of XRF Instrument
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•Applications
Bulk chemical analyses of major elements (Fe, Mn, Mg, Ca, Na, K, P) in
formulations.
Bulk chemical analyses of trace elements (in abundances >1 ppm; Ce, Cr,
Cu, Ni, Rb, Sr, Rh, Zn)
Environmental studies (e.g., analyses of particulate matter on air filters)
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Case Study
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Name of
Author
Study Result /
conclusio
n
S. Al-
Omari
Detection
of trace
element in
ten herbal
medicine
The Hg
was found
beyond
the
permitted
value
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3. Atomic Absorption Spectroscopy (AAS)
It is a technique for measuring the concentration of various elements inthe sample through their absorption of light.
It is a relatively simple and reliable technique which uses absorption ofoptical radiation by free atoms for determining the contents of differentelements.
Fig-Shimadzu AA-6800
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•Working of AAS Instrument
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•Detection limit in ppm of AAS
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Element Detection Limit
Range in ppm
AAS detected
range in ppm
Cadmium(Cd) 0.001-0.020 0.001
Chromium(Cr) 0.001-0.020 0.003
Mercury(Hg) 0.001-0.020 0.5
Lead(Pb) 0.001-0.020 0.01
Copper(Cu) 0.001-0.020 0.002
Nickel (Ni) 0.001-0.020 0.005
Sodium(Na) 0.001-0.020 0.002
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•Applications
Atomic spectroscopy is used for quantitative analysis of
metal elements in any sample.
It is specially useful to analyze trace metal elements in plasma and
other body fluids.
To determine metal elements in food industry.
In Forensic Science
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Case Study
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Name of
Author
Study Result /
conclusion
Somvir
Bajar and
et-al
Investigation
of heavy
metal conc.in
medicinal
plant collected
from different
areas.
The
Chromium
was found
beyond the
permitted
limit more
than 2 ppm
as per
WHO.
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4. Inductively Coupled Plasma-Mass Spectroscopy (ICP-MS)
This technology couples use of an ICP with MS for elemental analysis by
generation of ions.
The ICP is involved in generation of a high temperature plasma source at
10,000 degree Celsius, through which the pre-treated sample is passed.
The elements in the sample at such high temperature are ionized and
directed further into the MS.
The MS then sorts the ions according to their mass/charge ratio followed
by directing them to an electron multiplier tube detector.
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•Working of ICP-MS Instrument
Fig- Agilent 7700 ICP-MS
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•Applications
One of the largest volume uses for ICP-MS is in the medical and
forensic field, specifically, toxicology.
Heavy metal detection.
ICP-MS is used for detecting inorganic impurities
in pharmaceuticals and their ingredients.
ICP-MS is also used widely in the geochemistry field for radiometric
dating, in which it is used to analyze relative abundance of different
isotopes, in particular uranium and lead.
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Unapproved Herbal Product Analyzed by Health Canada
Name of Herbal
Product
Manufacturer City / Country Heavy metal found
Karela Tablet Shriji Herbals India Lead
Karela Capsule Himalaya Drug Co India Lead
Maha Sudarshan
Churna
Zandu
Pharmaceuticals
Mumbai, India Mercury , Lead
Maha Sudarshan
Churna
Dabur India Ltd New Delhi, India Mercury , Lead
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Solution for avoiding heavy metal
• Good Agricultural Practices (GAP) and Good Agricultural & Collection
Practices(GACP) include use of good fertilizers and provision of integrated
disease management.
• Adopt GMP in processing and manufacturing Process in industry.
• The standard operative procedures (SOP) should be adopted at every stage
of drug preparation and it starts with careful selection of standard raw
materials free of contaminants.
• Quantitative analysis of heavy metals should be done on raw materials of
herbal drugs. e.g. Spectroscopy.
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Conclusion
• Heavy metal are toxic to health if they are not used in proper form as
well as kept below certain concentration as described earlier.
• The proper method to be followed during manufacturing of product
can minimize the contamination of heavy metal.
• Adopt GAP(Good Agriculture Practices ).
• The GMP practice should be adopted during processing and
manufacturing of product.
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References
• The Ayurvedic Pharmacopoeia of India, Part-I, Vol-I, First Edition,
Page no-147-151.
• Skoog, Holler and Nieman Principles of Instrumental Analysis, Fifth
Edition ,Page no-206-225, 288-296.
• Desideri, D., Meli, M. A., Roselli, C., & Feduzi, L. (2011).
Determination of essential and non-essential elements in herbal tea
and camomile by polarised X rays fluorescence spectrometer
(EDPXRF). Journal of Radioanalytical and Nuclear Chemistry,
290(2), 391–396.
• Ernst, E. (2002). Toxic heavy metals and undeclared, 23(3), 136–139.
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Cont …
• Sukender, K., Jaspreet, S., Sneha, D., & Munish, G. (2012). AAS
Estimation of Heavy Metals and Trace elements in Indian Herbal Cosmetic
Preparations, 2(3), 46–51.
• Tokalıoğlu, Ş. (2012). Determination of trace elements in commonly
consumed medicinal herbs by ICP-MS and multivariate analysis. Food
Chemistry, 134(4), 2504–2508.
• USP <232> / <233> and ICH Q3D Elemental Impurities Analysis : Agilent ’
s ICP-MS solution White paper. (2017).
• Yuan, X., Chapman, L., & Wu, Z. (2011). Analytical Methods for Heavy
Metals in Herbal Medicines, (February), 189–198.
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Cont…• Kulhari, A., Sheorayan, A., Bajar, S., Sarkar, S., Chaudhury, A., & Kalia, R.
K. (2013). Investigationof heavy metals in frequently utilized medicinal
plants collected from environmentally diverse locations of north western
India, 2050, 1–9.
• Safety, F., Authority, S., Health, M. O. F., Welfare, F., & Delhi, N. E. W.
(2015). MANUAL OF METHODS OF ANALYSIS OF FOODS METALS.
• Heavy Metals : Analysis and Limits in Herbal Dietary Supplements. (2009),
(December).
• Al-Omari, S. (2011). Determination of essential and toxic trace elements in
ten herbal medicines using energy-dispersive XRF analysis. X-Ray
Spectrometry, 40(1), 31–36.
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Thank You…..!!!!!
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