“ 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

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

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

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

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

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

•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

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

•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.

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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