PREFACE TO THE UPDATED EDITION

WHO published Quality control methods for medicinal plant materials in 1998, in order
to support WHO Member States in establishing quality standards and
specifications for herbal materials, within the overall context of quality assurance
and control of herbal medicines. This publication came to be regarded as one of
the key technical documents in ensuring and controlling the quality of herbal
medicines.
At the end of 2007, the document WHO guidelines on assessing quality of herbal
medicines with reference to contaminants and residues was published. These two
publications were the result of joint activities between, among others, the teams of
Quality and Safety: Medicines (QSM) and Traditional Medicine (TRM) within the
WHO Cluster for Health Systems and Services.
The majority of adverse events reported in relation to the use of herbal products and
herbal medicines are attributable to poor quality of the product. In order to
promote the safety of herbal medicines, WHO has committed itself to develop the
necessary new guidelines and to update existing ones relating to the quality
assurance and control of herbal medicines.
The preparation of the guidelines relating to contaminants and residues gave WHO an
opportunity to gather detailed technical information on various analytical methods
for determining possible contaminants and residues in herbal medicines —
including those described in 10 national and/or regional pharmacopoeias.
Subsequently, WHO was able to compare each analytical method for specific
contaminants and residues and could recommend methods for each of the possible
contaminants and residues of herbal medicines. This material was identified to
serve in updating the information and methods corresponding to sections 16–22 of
Quality control methods for medicinal plant materials (1998).
As the Quality control methods for medicinal plant materials was widely distributed,
WHO considered reprinting the publication. However, in view of the
abovementioned opportunity given by the development of the guidelines, it was
proposed to update the relevant sections and publish an updated edition instead of
reprinting the existing publication. In 2004, the WHO Expert Committee on
Specification of Pharmaceutical Preparations agreed with this proposal.
Subsequently, draft chapters for the update were consolidated and were presented to the
WHO Expert Committee on Specifications for Pharmaceutical Preparations at its
consultation meetings and sessions in 2005 and 2006. At its 2007 session, the
Expert Committee the publication of the updated edition.
The purpose of this updated edition remains unchanged from that of the first edition. It is
to support the development of national standards based on local market conditions,
with due regard to existing national legislation and national endorsedQuality
control methods for herbal materials x and regional norms. It describes a series of
tests for assessing the quality of herbal materials, including the determination of
pesticide residues, arsenic and toxic heavy metals, microorganisms and aflatoxins.
This new edition will also serve as key technical training material in capacity-
building training workshops in herbal medicines. Compilation of the updated
edition of Quality control methods for medicinal plant materials — now with the
updated title of Quality control methods for herbal materials — has been
undertaken thanks to continued collaboration between QSM and TRM. This
publication is an example of the immediate response of WHO in the
implementation of the Global strategy and plan of action on public health,
innovation and intellectual property that was adopted by the Sixty-first World
Health Assembly.
As this publication was being prepared, the WHO Expert Committee on Specifications
for Pharmaceutical Preparations adopted WHO good practices for pharmaceutical
quality control laboratories, which were published in 2010 as Annex 1 of the 44th
report of the Committee. The scope of the good practice guidance in this annex
includes pharmaceutical quality control laboratories handling herbal medicines. In
order to promote these good practices and to provide general technical guidance in
conducting the test methods described in this publication, Annex 1 of the Forty-
fourth report of the WHO Expert Committee on specifications for pharmaceutical
preparations is annexed to this publication for easy reference.

1. General notices
General considerations
The metric system is used throughout the text. All temperatures are expressed in
degrees Celsius (°C).
Tests are normally carried out at room temperature (15–25 °C, or up to 30 °C in
some climatic zones), unless otherwise indicated.
Any glassware used in the tests should be of suitable quality. Graduated and
volumetric vessels should be calibrated at room temperature.
 When a water-bath is referred to in the text, a bath containing boiling water (about
100 °C) is to be used, unless a specific water temperature is given.
Unless otherwise specified, all solutions indicated in the tests are prepared with
distilled or demineralized water of adequate purity.
Reagents and solutions
Reagents and solutions used must conform to the requirements specified in chapter
23 on “Reagents and solutions”, and are designated as follows: reagent, R; test
solution, TS; volumetric solution, VS.
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 as follows: — a value of
20.0 means not less than 19.5 and not more than 20.5; — a value of 2.0 means not
less than 1.95 and not more than 2.05; — a value of 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 in some climatic zones.
pH values
Precision in the measurement of pH values is indicated in a manner similar to that
for quantities and volumes.
Calculation of results
The results of tests and assays should be calculated to one decimal place more than
indicated in the requirement and then rounded up or down, as follows:
— if the last figure calculated is 5 to 9, the preceding figure is increased by 1;
— if the last figure calculated is 4 or less, the preceding figure is left unchanged.
 Other calculations, such as in the standardization of volumetric solutions, should
be carried out in a similar manner.
If the material has to be dried before it can be reduced to a powder for use in a
determination, a correction must be made to take into account the loss on drying,
and the amount of active principle calculated with reference to the undried sample.
Establishment of limits
Reasonable limits may be established using simple statistical methods (e.g.
control chart techniques) (1,2). Analytical results from about 20 successive
batches are pooled together, and the grand average and “three sigma limits” (±3
standard deviations from the grand average) are calculated. Such calculations are
applicable when more than one individual or independent sample per batch is
analysed (3,4).
Solubility
Unless otherwise specified in the test procedure for the plant material concerned,
the approximate solubility of herbal 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 10 000 parts.
Storage
Herbal materials must be stored under specified conditions in order to avoid
contamination and deterioration.3 General notices
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:
- Well-closed containers must protect the contents from extraneous matter or from
loss of the material under normal conditions of handling, shipment or storage.
- Tightly closed containers 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.
- Hermetically closed containers must protect the contents from extraneous matter
and from loss of the substance, and must be impervious to air or any other gas
under normal conditions of handling, shipment or storage.
In addition, a tamper-evident container is one that is fitted with a device that
reveals clearly whether it has ever been opened.
Protection from light
Herbal 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 (15–
25 °C or, depending on the climate conditions, up to 30 °C) 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
Herbal materials are used either whole, or in cut or powdered form.
Cut herbal 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
Units of measurement
The names and symbols for units of measurement used in this manual conform
with those used in The international pharmacopoeia (5) and those of the
International System of units (SI), developed by the General Conference of
Weights and Measures (CGPM) in collaboration with other international
organizations (6,7).