Transcript phg 431 (2nd lecture..

Quality control of herbal drugs
Quality control is a multistep process that covers
all stages from the growing of the botanical
material to the finished product and the
evaluation of its stability and quality over time
1- The quality of the botanical material used which
influenced by a multitude, climatic factors and
also the risk of contamination.
2- The adequate processing of the fresh material
including drying, transportation and storage.
3- The use of a suitable extraction technique.
4Storage
under
appropriate
generally, dry, cool in the dark.
conditions,
5- Use of the material within the accepted shelflife of the botanical drug.
1- The correct botanical identity of the drug (the
correct species and plant part) and the appropriate
quality (time of collection, age).
2- The purity of the material used.
3- Contaminants such as insecticides, pesticides, etc…
are below the legal limits.
4- The required level of active compounds is reached.
The best level of quality control can be achieved if all
the requirements are defined in a monograph in a
legal pharmacopoeia.
1- Title (English name, Latin name).
2- Definition of the drug.
3- characteristics: organoleptic or other properties of the drug.
4- Identification: macroscopically and microscopically and in some
cases thin layer chromatographic characteristics.
5-Tests for purity: maximum amount of foreign matter, loss on
drying, ash.
6- Required level of biologically active compounds.
7- Storage, general information about required forms of storage.
Pharmaceutical drugs have to comply with all
the characteristics as they are defined in such
a monograph and material that does not
comply must be rejected.
1- Botanical name, with reference to the authors.
2- Specification of the part used.
3- Morphological description, macro and microscopic
examination.
4- Determination of particle size distribution.
5- Determination of total ash or sulfated ash (residue on
ignition) and acid insoluble ash.
6- Determination of extractable matter.
7- Determination of water and loss on drying.
8- Determination of essential oils.
9- Identification by thin layer chromatography.
10Quantitative
constituents.
determination
of
11- Limit tests for heavy metals.
12- Determination of pesticide residues.
active
Is due to Swedish biologist Linnaus, in this system
the first name, which is always spelt with Capital
letter, denotes the genus.
whilst the second name denotes the species. It is
however, still equally correct to use capital where
the species is named after a person.
Thus the species of Cinchona named after Charles
Ledger, who brought its seed from Brazil 1865, is
known as Cinchona Ledgeriana.
Examples:
Glycyrrhiza glabra
Atropa belladonna
Citrus aurantium
Myristica fragrans
Cannabis indica
Strychnos nux vomica
Allium sativum
Hyoscyamus muticus
Piper nigrum
Digitalis purpurea
Caryophyllus aromaticus
Papaver somniferum
Ipomoea purga
Panax ginseng
The flower is a modified fertile shoot, carrying modified
leaves, highly specialized for performance of
reproductive function and adapted to produce fruits
and seeds, i.e. for the propagation of the individual.
A typical flower is usually formed of four sets of floral
leaves arranged on a shortened axis (flower stalk or
pedicel), the swollen or expanded apex of which is
called receptacle.
The calyx: composed of sepals.
The corolla: composed of petals.
The petals and sepals when all
alike called perianth.
The
andrœcium
(male
organ):
composed of stamens; each stamen
composed of anther and filament).
The gynæcium (pistil, female organ):
composed of carpels; each carpel
composed of ovary, style and
stigma.
Stigma
Anthe
Stamen
r
Filament
Style
Pistil
Ovary
Ovule
Petals
Sepals
Pedicel
Courtesy of McGraw Hill Publishers
Swollen base
where are parts
attach
Receptacle
These are openings in the epidermis of stem
and leaves. They occur in both surfaces or
only on lower surface. In water plants they
occur in upper surface.
Types of stomata:
The types are indicated either with regard to
the characters of the guard cells or with
regard to the epidermal cells surrounding the
stomata.
1Ranunculaceous
or
Anomocytic
stomata
(irregular
celled):
The
surrounding
cells
(subsidiary cells) are of
varying number have no
special arrangement and
generally do not differ from
other epidermal cells e.g.
Digitalis.
2Rubiaceous
or
Paracytic
(parallel
celled): the stoma is
surrounded by two or
more subsidiary cells,
two of which have their
long axes parallel to
the osteole e.g. Senna.
3-Caryophyllaceous
or
Diacytic (cross celled):
the stoma is surrounded
by
subsidiary
cells
having their long axes
perpendicular
to
the
osteole e.g. Mentha.
4Cruciferous
or
Anisocytic
(unequal
celled): the stoma is
surrounded by usually
three
or
more
subsidiary cells one of
which
is
distinctly
smaller than the others
e.g. Belladonna.
The important identifying
constants like:
characteristic
1- Stomatal Number
2- Stomatal Index
3- Vein-islet number
4- Veinlet termination number
of
leaf
1- Stomatal number :
It is the average number of stomata per square mm of the
epidermis of the leaf .
2- Stomatal index
Stomatal index is the percentage which the number of
stomata forms to the total number of epidermal cells,
each stomata being counted as one cell. Stomatal index
can be calculated by using following equation .
S = No. of stomata per unit area ,
E = No. of epidermal cells in the same unit area .
3- Vein-islet number
A vein-islet is the small area of green tissue
surrounded by the veinlets.
The vein-islet number is the average number of
vein-islets per square millimeter of a leaf surface.
4- Veinlet termination number
Veinlet termination number is defined as the number
of veinlet termination per sq. mm of the leaf
surface, midway between midrib of the leaf and its
margin
This provides a process of assay for drugs, such as linseed
which contains fixed oil as an important constituents and
the yield to ether is a means of assay.
Aqueous extract of Liquorice provides an assay process.
High petroleum ether extract in case of colocynths indicates
adulteration with the seeds of colocynths fruit.
The amount of insoluble matter also will indicate the
presence of an unreasonable amount of woody matter or
pieces of bark or of vegetable debris in drugs such as
myrrh.
The determination of ash is useful for detecting low grade
drugs, exhausted drugs and excess of sandy or earthy
matter.
A total ash is useful to exclude drugs which have been
coated with chalk, lime e.g. ginger and nutmeg.
The acid insoluble ash: in case of drugs like rhubarb with
variable amount of calcium oxalate total ash will vary 840% and so acid insoluble ash is more useful as all calcium
will dissolved in HCl. In this way one can obtain evidence
of the presence of excessive earthy matter.
The water soluble ash: is used to detect the presence of
material exhausted by water and is used more especially
for tea leaves and ginger rhizome.
Herbal drugs may be contaminated with several
contaminants:
Pesticides,
aflatoxines,
heavy
microorganisms, radioactivity.
metals,
Pesticides are broadly defined as a substance or mixture
intended to prevent, destroy or repel any pest including
insect, reodents and weeds. They include not only
insecticides but also herbicides, fungicides, disinfectants
and growth regulators.
Pesticides are generally categorized based upon their
persistence in the environment. Organochlorine pesticides
are considered persistent pesticides. These pesticides
have long environmental half-lives and tend to
bioaccumulate in humans and other animals.
The contemporary pesticides include organophosphates,
carbamates,
triazines,
chloroacetanilides,
synthetic
pyrethroides and others and are considered nonpersistent.
These pesticides have much shorter environmental half-lives
and tend not to bioaccumulate.
They are organochlorine compounds e.g. DDT
They can be estimated in the plants by liquid extraction
and analyzed using gas chromatography (GC) with
electron capture detector (ECD).
1.2. Non-persistent pesticides
Includes:
a- insecticides: organophosphates,
carbamates, pyrethroids: they are analyzed by
different chromatographic techniques.
b- herbicides: triazines, phenoxyacids,
chloroacetanilides, others
Aflatoxins
are
coumarin
derivatives.
They
were
detected for the first time in
1960, when 100000 turkey
died as a result of feeding on
groundnut
meal
contaminated by Aspergillus
flavus, a fungus producing a
number of toxins, which were
called aflatoxins.
Aflatoxins affect many organs and tissues; the major
problems being hepatotoxicity and liver carcinogenesis.
The monograph for each herbal drug shows
limits for heavy metal content, with reference
to the dried matter
Lead: 5 mg/kg
Cadmium: 0.2 mg/kg
Mercury: 0.1 mg/kg
Each natural material naturally harbors a large
number of spores and other microorganisms. The
maximum number of microorganisms allowed is
regulated in different pharmacopoeias

Up to 105 aerobic microorganisms per g or ml,
including: Up to 103 yeast and fungi per g or ml
and up to 103 enterobacteria per g or ml.

No detectable E. coli (in 1 g or ml)

No detectable Salmonella sp. (in 10 g or ml)
Although testing on radioactivity is no longer
legally
required,
manufacturers
should
perform such tests in practice at their own
responsibility
in
case
radioactive
contamination is suspected in medicinal
plants.