Pharmacognosy

Professor in Pharmacy

Friday, September 14, 2012

Quality control methods for medicinal plant materials

Quality control methods for medicinal
plant materials

My dear, I have taken this all material from  Quality control methods for medicinal plant materials, WHO Library Cataloguing in Publication Data, World Health Organization 1998

 Precision of measurement

Quantities and volumes
The quantities and volumes of the materials and reagents used in the tests must be measured with adequate precision, which is indicated in the following way:
A value of: 
20.0 means not less than 19.5 and not more than 20.5 
2.0 means not less than 1.95 and not more than 2.05
0.20 means not less than 0.195 and not more than 0.205.

Temperature

Temperature measurement is indicated in a manner similar to that given for quantities and volumes.
Storage conditions given in general terms refer to the following equivalent temperatures:
In a refrigerator                                     0-6 °C
Cold or cool                                           6-15 °C
Room temperature                                  15-25 °C,
or up to 30°C depending on climatic zones.

 

Solubility
Unless otherwise specified in the test procedure for the plant material concerned, the approximate solubility of medicinal plant materials should be determined at 20°C. Solubility is expressed in terms of "parts", representing the number of millilitres (ml) of the solvent, in which 1 g of the solid is soluble. Descriptive terms are sometimes used to indicate the solubility of a substance, with the following meanings:

 

very soluble                                  less than 1 part
freely soluble                               1-10 parts
soluble                                          10-30 parts
sparingly soluble                          30-100 parts
slightly soluble                             100-1000 parts
very slightly soluble                     1000-10 000 parts
practically insoluble                      more than 10000 parts

 

Storage
Medicinal plant materials must be stored under specified conditions in order to avoid contamination and deterioration.

Containers
The container and its closure must not interact physically or chemically with the material within in any way that would alter its quality. The following descriptive terms are used to indicate general requirements for the permeability of containers:

A well-closed container must protect the contents from extraneous matter or from loss of the material under normal conditions of handling, shipment, or storage.
A tightly closed container must protect the contents from extraneous matter, from loss of the material, and from efflorescence, deliquescence, or evaporation under normal conditions of handling, shipment, or storage. If the container is intended to be opened on several occasions, it must be designed to be airtight after reclosure.

Protection from light

Medicinal plant materials requiring protection from light should be kept in a light-resistant container that - either by reason of the inherent properties of the material from which it is made or because a special coating has been applied to it - shields the contents from the effects of light. Alternatively, the container may be placed inside a suitable light-resistant (opaque) covering and/or stored in a dark place.

Temperature
Materials that need to be stored at temperatures other than room temperature should be labelled accordingly.

Humidity

Low humidity may be maintained, if necessary, by the use of a desiccant in the container provided that direct contact with the product is avoided. Care must be taken when the container is opened in damp or humid conditions.

Size of cut

Medicinal plant materials are used either whole, or in cut or powdered form. Cut medicinal plant materials are prepared by cutting or crushing the plant into small pieces. The cut is graded according to the aperture size of the mesh of the sieve through which the material will pass, and is indicated as follows:

 

Aperture size                      (mm)
coarse cut                           4.00
medium cut                        2.80
fine cut                               2.00

 

Powder fineness and sieve size

Powders
The coarseness or fineness of a powder is classed according to the nominal aperture size expressed in hum of the mesh of the sieve through which the powder will pass, and is indicated as follows:

Descriptive term Particle size

Coarse (2000/355) All the particles will pass through a No. 2000 sieve, and not more than 40% through a No. 355 sieve

Moderately coarse (710/250) All the particles will pass through a No. 710 sieve, and not more than 40% through a No. 250 sieve

Moderately fine (355/180) All the particles will pass through a No. 355 sieve, and not more than 40% through a No. 180 sieve

Fine (180) All the particles will pass through a No. 180 sieve

Very fine (125) All the particles will pass through a No. 125 sieve

Sieves

The wire sieves used to sift powdered medicinal plant materials are classified by numbers that indicate their nominal aperture size expressed in μm. The sieves are made of wire of uniform circular cross-section, and have the following specifications:

Number of sieve Nominal size of aperture  Nominal diameter of wire.    

Approximate screening area
(μm)                      (mm)                                     (mm)                                       (%)
2000                      2.00                                        0.90                                         48
710                        0.710                                      0.450                                       37
500                        0.500                                      0.315                                       38
355                        0.355                                      0.224                                       38
250                        0.250                                      0.160                                       37
212                        0.212                                      0.140                                       36
180                        0.180                                      0.125                                       35
150                        0.150                                      0.100                                       36
125                        0.125                                      0.090                                       34
90                          0.090                                      0.063                                       35
75                          0.075                                      0.050                                       36
45                          0.045                                      0.032                                       34


The sieves recommended here have been selected from among those conforming to ISO standard 565, 1990.

Determination of foreign matter

Medicinal plant materials should be entirely free from visible signs of contamination by moulds or insects, and other animal contamination, including animal excreta. No abnormal odour, discoloration, slime or signs of deterioration should be detected. It is seldom possible to obtain marketed plant materials that are entirely free from some form of innocuous foreign matter.

However, no poisonous, dangerous or otherwise harmful foreign matter or residue should be allowed.
During storage, products should be kept in a clean and hygienic place, so that no contamination occurs. Special care should be taken to avoid formation of moulds, since they may produce aflatoxins.

Macroscopic examination can conveniently be employed for determining the presence of foreign matter in whole or cut plant materials. However, microscopy is indispensable for powdered materials.

Any soil, stones, sand, dust and other foreign inorganic matter must be removed before medicinal plant materials are cut or ground for testing.


Foreign matter is material consisting of any or all of the following:

- parts of the medicinal plant material or materials other than those named with the limits specified for the plant material concerned;

- any organism, part or product of an organism, other than that named in the specification and description of the plant material concerned;

- mineral admixtures not adhering to the medicinal plant materials, such as soil, stones, sand, and dust.

Sample size

It is difficult to prepare a pooled sample of foreign matter since most of it adheres to the medicinal plant materials which are intrinsically non-uniform.

Special procedures requiring considerable practice are therefore necessary. The problem is especially difficult when the samples of unbroken crude medicinal plant materials selected are small; they should be sufficiently large to be representative.

The following quantities constitute a sample, unless otherwise specified in the test procedure for the plant material concerned.


Plant material Sample size
roots, rhizomes, and bark                                                                                                500 g
leaves, flowers, seeds, and fruit                                                                                      250 g
cut medicinal plant materials (average weight of each fragment less than 0.5 g)         50g

Visual examination and odour

Wrinkled and contracted leaves, herbs or flowers should be softened and stretched flat ("Preliminary treatment"). Certain fruits and seeds may also require softening before dissection and observation of internal characteristics. No other preliminary treatment is required.

Recommended procedures

Size
A graduated ruler in millimetres is adequate for the measurement of the length, width and thickness of crude materials. Small seeds and fruits may be measured by aligning 10 of them on a sheet of calibrated paper, with 1 mm spacing between lines, and dividing the result by 10.

Colour

Examine the untreated sample under diffuse daylight. If necessary, an artificial light source with wavelengths similar to those of daylight may be used. The colour of the sample should be compared with that of a reference sample.

Surface characteristics, texture and fracture characteristics Examine the untreated sample. If necessary, a magnifying lens (6x to 10x) may be used. Wetting with water or reagents, as required, may be necessary to observe the characteristics of a cut surface. Touch the material to determine if it is soft or hard; bend and rupture it to obtain information on brittleness and the appearance of the fracture plane - whether it is fibrous, smooth, rough, granular, etc.

Odour

If the material is expected to be innocuous, place a small portion of the sample in the palm of the hand or a beaker of suitable size, and slowly and repeatedly inhale the air over the material. If no distinct odour is perceptible, crush the sample between the thumb and index finger or between the palms of the hands using gentle pressure. If the material is known to be dangerous, crush by mechanical means and then pour a small quantity of boiling water onto the crushed sample in a beaker. First, determine the strength of the odour (none, weak, distinct, strong) and then the odour sensation (aromatic, fruity, musty, mouldy, rancid, etc.). A direct comparison of the odour with a defined substance is advisable (e.g. peppermint should have an odour similar to menthol, cloves an odour similar to eugenol).

Taste
N.B. This test should be applied only if specifically required for a given plant material.
Inspection by microscopy

Once the material has been examined and classified according to external characteristics, inspection by microscopy can be carried out as the next step.

Equipment
The following are required: - a microscope equipped with lenses providing a wide range of
magnification and a substage condenser, a graduated mechanical stage, objectives with a magnification of 4x, 10x, and 40x, and colour filters of ground glass, blue-green; high eyepoint eyepieces are preferred for wearers of spectacles;

- a lamp, either separate or incorporated into the microscope;

- a set of polarizing filters;

- a stage micrometer and an ocular micrometer to be inserted into a 6x eyepiece and placed

on the diaphragm or, preferably, a micrometer eyepiece;

- a set of drawing attachments for the microscope;

- a microburner (Bunsen type);

- slides and cover-glasses of standard size;

- a set of botanical dissecting instruments.

Recommended procedures

Preliminary treatment

Select a representative sample of the material. Dried parts of a plant may require softening before preparation for microscopy, preferably by being placed in a moist atmosphere, or by soaking in water. For small quantities of material, place a wad of cotton-wool moistened with water into the bottom of a test-tube and cover with a piece of filter-paper. Place the material being examined on the paper, stopper the tube and allow to stand overnight or until the material is soft and suitable for cutting. Use a desiccator for larger quantities of material, placing water into the lower part instead of the drying agent. Bark, wood and other dense and hard materials usually need to be soaked in water or equal parts of water, ethanol and glycerol for a few hours or overnight until they are soft enough to be cut. Boiling in water for a few minutes may sometimes be necessary.

Any water-soluble contents can be removed from the cells by soaking in water. Starch grains can be gelatinized by heating in water. In certain cases, material can be moistened with water for a few minutes to soften the surfaces and allow sections to be cut.

Preparation of specimens

Powdered materials

Place 1 or 2 drops of water, glycerol/ethanol TS or chloral hydrate TS on a glass slide. Moisten the tip of a needle with water and dip into the powder. Transfer a small quantity of the material that adheres to the needle tip into the drop of fluid on the slide. Stir thoroughly, but carefully, and apply a cover-glass. Press lightly on the cover-glass with the handle of the needle, and remove excess fluid from the margin of the cover-glass with a strip of filter-paper. Other fluids may be used, if necessary, in the same manner.

If the specimen is to be freed from air bubbles, boil carefully over a small flame of a microburner until the air is completely removed. Care should be taken to replace the fluid that evaporates so that the space beneath the cover-glass is completely filled with fluid at the conclusion of the operation.

Surface tissues of leaves and flowers

To render pieces of thin leaves transparent, boil them directly on a slide. Cut a piece of leaf into two portions, turn one piece upper side down and add chloral hydrate TS. Boil the specimen carefully over a small flame of a microburner and, as soon as bubbles escape, remove the slide from the flame. When the bubbles have ceased to appear, boil again until the fragments are transparent.

For slightly thicker but still papery leaves, cut square pieces, about 6 mm from the edge of the leaf, if not otherwise specified. The pieces should be taken onethird to one-half of the way from the leaf-base and should include a midrib or large vein. In addition, cut 1 or 2 pieces from the edge including 1 or 2 indentations, where appropriate. For broken or cut leaves take suitable fragments as described above. Place the fragments in a test-tube containing chloral hydrate TS and boil for a few minutes until they become transparent. Transfer a fragment to a slide and cut it into two equal portions. Turn one piece upper side down and align the two pieces so that both upper and lower surfaces can be observed under the microscope. Add 1-2 drops of chloral hydrate TS and apply a cover-glass.
For thicker leaves, that do not become transparent enough when prepared by the method described above, clarify fragments by boiling with chloral hydrate TS in a test-tube. Transfer a fragment onto a slide, cut it into two equal portions and turn one portion upper side down. Scrape the surface of the two portions using a scalpel until only a single layer of epidermis remains. Wash the epidermis with drops of chloral hydrate TS or glycerol /ethanol TS to remove any residues. If possible, turn both parts of the epidermis upper side down, and add one of the above fluids.

For very thick or fleshy leaves, pull off the upper and lower parts of epidermis by winding the softened leaf around the index finger, pressing with the thumb and the middle finger against the index finger and carefully incising, catching the incised part with forceps, and bending the epidermis backwards carefully.

Petals and sepals of flowers may be treated in a similar manner.

Sections

Select representative pieces of the material being examined and cut into suitable lengths, one end of which is softened and smoothed. Prepare cross or transverse sections by cutting with a razor blade or microtome at a right angle to the longitudinal axis of the material. Prepare longitudinal sections by cutting in parallel with the longitudinal axis, either in a radial direction (radial section) or in a tangential direction (tangential section).

Thick materials, such as wood, woody stems, rhizomes and roots can be cut by holding the softened material between the thumb and index finger, supported by the middle finger or by holding it in the central hole of a hand microtome.

Thin materials such as leaves, petals and slender stems should be bound between two halves of a piece of elder-pith or other suitable support. If necessary, moisten the surface to be cut and the blade with ethanol (375 g/l) TS. Cut the sections as thinly and evenly as possible. Transfer the sections with a brush moistened with ethanol (150g/l) TS to a dish containing ethanol (150g/l) TS. Select satisfactory sections for the preparation of the slides. For certain materials a sliding microtome may be used. Seeds and fruits that are very flat, or that are small and spherical, and cannot be held in the manner described above may be inserted into a notch cut into a small rubber stopper or embedded in hard paraffin (paraffin wax) as follows. Prepare a hard paraffin block, rectangular in shape, measuring about 7 x 7 x 15 mm, and melt a small hole in the centre of one end using a heated needle or thin glass rod. Press the material, which should be dry or softened by exposure to moisture, into this hole. Then prepare sections with a microtome. For the examination of mucilage, aleurone grains or spherical aggregations of inulin, cut the material without using water.

Clarification of microscopic particles

The presence of certain cell contents, such as starch grains, aleurone grains, plastids, fats and oils, may render sections non-translucent and obscure certain characteristics. Reagents that dissolve some of these contents can be used in order to make the remaining parts stand out clearly or produce a penetrating effect. This renders the section more transparent and reveals details of the structures.

If the refractive index of the clarifying agent is close to that of the cell structure, the material being tested becomes almost invisible; if it differs appreciably, the material becomes markedly evident.

The most frequently used clarifying agents are described below (for the methods of preparation, see section 22, "Reagents and solutions").

Chloral hydrate TS
On gentle heating chloral hydrate TS dissolves starch grains, aleurone grains, plastids, and volatile oils, and expands collapsed and delicate tissue without causing any undue swelling of cell walls or distortion of the tissues. It has a refractive index ( n ) of 1.44 -1.48. It is the best reagent for rendering calcium oxalate clearly evident and is particularly useful for small crystals. However, when allowed to stand, it slowly dissolves calcium oxalate, owing to an increase in acidity.

 Measurement of specimens

Equipment
Use a microscope with an ocular micrometer to measure the size of small objects. The scales should be calibrated using a stage micrometer, consisting of a glass slide of usual size, upon which a scale is engraved or photographed, usually 1 or 2 mm long, in 0.1 and 0.01 mm divisions. The ocular micrometer consists of a small disc of glass, across the diameter of which a 100-line scale is engraved or photographed. The disc is placed into the eyepiece.


Calibration of the ocular micrometer

Place the ocular micrometer scale in the eyepiece of the microscope. Put the stage micrometer on the microscope stage and focus on the scale divisions. Both scales should be sharply defined in the field of view. Turn the eyepiece to place the scales in a parallel position and, if necessary, move the stage micrometer until the starting lines of both scales coincide (Fig. 1). Now find another point, as far along the scale as possible, where two other division lines are exactly superimposed. Count the number of divisions on the ocular micrometer and the corresponding length on the stage micrometer scale, in order to determine the length that is equivalent to one division on the ocular micrometer scale; for example, if 100 divisions on the ocular micrometer scale are equal to 30 divisions on the stage micrometer scale, since the divisions on the stage micrometer scale are 0.01 mm apart, 100 ocular micrometer divisions are equivalent to 0.30 mm, therefore each division on the ocular micro-meter scale represents 3.0 μm. Since the calibrations apply only for a particular lens combination, it is advisable to determine and record the ocular micrometer values for the most frequently used combinations.

Alignment of the stage micrometer and the ocular micrometer 

Method
Place the specimen on the microscope stage and focus on the object to be measured. Superimpose the ocular micrometer scale and read off the dimensions of the object. Multiply the number of scale divisions by the micrometer value to give the actual dimension in micrometres. By this method, using a 40x objective and a 6x eyepiece, measurements are correct to the nearest 2 μm, i.e. a dimension of 20 μm is liable to an error of 2 μm, or 10%, or ±5%; a dimension of 100 μm is liable to an error of 2% or ±1%.

For curved and elongated objects, the measurement of lengths may be made using a microscope equipped with a drawing apparatus or a camera lucida. The instrument should be set up so that the image of the object, the drawing paper and the pencil are in focus simultaneously. With the stage micrometer in place, trace the lines of the stage micrometer scale upon the paper fastened on a drawing board. Tilt the drawing board, if necessary, until the divisions drawn upon the paper are equally spaced. The magnification is determined by measuring the distance between selected lines on the drawing paper and dividing by the distance between the corresponding lines on the stage micrometer. Place the specimen on the microscope stage and trace the image of the object on the paper. Superimpose a coloured thread along the length of the object drawn on the paper and after straightening it, measure the length of the thread using a ruler graduated in millimeters; divide the measured length by the magnification to give the actual length of the object.

 Leaf stomata

Types of stoma

In the mature leaf, four significantly different types of stoma are distinguished by their form and the arrangement of the surrounding cells, especially the subsidiary cells: 

• The anomocytic or ranunculaceous (irregular-celled) type; the stoma is surrounded by a varying number of cells, generally not different from those of the epidermis.
• The anisocytic or cruciferous (unequal-celled) type; the stoma is usually surrounded by three or four subsidiary cells, one of which is markedly smaller than the others.
• The diacytic or caryophyllaceous (cross-celled) type; the stoma is accompanied by two subsidiary cells, the common wall of which is at right angles to the stoma.
• The paracytic or rubiaceous (parallel-celled) type; the stoma has two subsidiary cells, of which the long axes are parallel to the axis of the stoma.

In describing an epidermis where certain stomata differ from the predominant type, the term applying to the majority of stomata is used.

Determination of the stomatal index

Place fragments of leaves, about 5 x 5 mm in size, in a test tube containing about 5 ml of chloral hydrate TS and heat on a water bath for about 15 minutes or until the fragments are transparent. Transfer a fragment to a slide and prepare it as described earlier, the lower epidermis uppermost, in chloral hydrate TS; place a small drop of glycerol/ethanol TS at one side of the cover-glass to prevent the material from drying. Examine under a microscope with a 40x objective and a 6x eyepiece, equipped with a drawing apparatus. Mark on the drawing paper a cross (χ) for each epidermal cell and a circle (o) for each stoma. Calculate the stomatal index as follows:


stomatal index = S x100

                            -------------------

                                E+ S

where S = the number of stomata in a given area of leaf E= the number of epidermal cells (including trichomes) in the same area of leaf.
For each leaf sample, no fewer than ten determinations should be carried out and the average index calculated.

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