Acacia

Acacia
(Ph Eur monograph 0307)
Ph Eur
Definition
Acacia is the air-hardened, gummy exudate flowing naturally from or obtained by incision of the trunk and branches of Acacia senegal L. Willdenow and other species of Acacia of African origin.
Characters
Acacia is almost completely but very slowly soluble, after about 2 h, in twice its mass of water leaving only a very small residue of vegetable particles; the liquid obtained is colourless or yellowish, dense, viscous, adhesive, translucent and weakly acid to blue litmus paper. Acacia is practically insoluble in alcohol.
It has the macroscopic and microscopic characters described under identification tests A and B.
Identification
A. Acacia occurs as yellowish-white, yellow or pale amber, sometimes with a pinkish tint, friable, opaque, spheroidal, oval or reniform pieces (tears) of a diameter from about 1 cm to 3 cm, frequently with a cracked surface, easily broken into irregular, whitish or slightly yellowish angular fragments with conchoidal fracture and a glassy and transparent appearance. In the centre of an unbroken tear there is sometimes a small cavity.
B. Reduce to a powder (355). The powder is white or yellowish-white. Examine under a microscope using glycerolR (50 per cent V/V). The powder presents angular, irregular, colourless, transparent fragments. Only traces of starch or vegetable tissues are visible. No stratified membrane is apparent.
C. To 2 ml of solution S (see Tests) add 8 ml of waterR; the solution is laevorotatory.
D. Examine the chromatograms obtained in the test for glucose and fructose. The chromatogram obtained with the test solution shows three zones due to galactose, arabinose and rhamnose. No other important zones are visible, particularly in the upper part of the chromatogram.
E. Dissolve 1 g of the powdered drug (355) in 2 ml of waterR by stirring frequently for 2 h. Add 2 ml of alcoholR. After shaking, a white, gelatinous mucilage is formed which becomes fluid on adding 10 ml of waterR.
Tests
Solution S
Dissolve 3.0 g of the powdered drug (355) in 25 ml of waterR by stirring for 30 min. Allow to stand for 30 min and dilute to 30 ml with waterR.

Radiopharmaceutical Preparations

Radiopharmaceutical Preparations
Dried Iodinated [125I] Fibrinogen1
Sodium Iodide [125I] Solution1
1Monograph suppressed by European Pharmacopoeia Commission on 1 January 2003.
2Monograph transferred to the British Pharmacopoeia (Veterinary).
3Monograph suppressed by European Pharmacopoeia Commission on 1 July 2003
Technical Changes
The following monographs in the BP 2003 have been technically amended since the publication of the BP 2002. This list does not include revised monographs of the European Pharmacopoeia. An indication of the nature of the change or the section of the monograph that has been changed is given in italic type in the right hand column.
Medicinal and Pharmaceutical Substances
ormulated Preparations: Specific Monographs
4Monograph transferred from Volume I (Medicinal Substances) to Volume III (Formulated Preparations).
Changes in Title
The following lists give the alterations in the titles of monographs of the British Pharmacopoeia 2002 that have been retained in the British Pharmacopoeia 2003.
The changes listed below have arisen following changes in titles of monographs of the European Pharmacopoeia.
The changes listed below have arisen following the change from dual-labelled titles to titles including only the recommended International Nonproprietary Names (see above). Consequential changes to the Labelling and Preparation(s) statements have also been made to these monographs, where appropriate.

Medicinal and Pharmaceutical Substances

Medicinal and Pharmaceutical Substances
Calcium Sodium Lactate
Capreomycin Sulphate
Cocillana
Corticotropin1
Hydroxyprogesterone Caproate
Isoaminile
Oxyphenbutazone1
Sulfadimidine2
Sulfadimidine Sodium
Formulated Preparations: General Monographs
Tinctures1
Formulated Preparations: Specific Monographs
Capreomycin Injection
Cloxacillin Capsules
Cloxacillin Injection
Cloxacillin Oral Solution
Docusate Tablets
Hydroxyprogesterone Injection
Lypressin Injection3
Macrogol Ointment
Oxyphenbutazone Eye Ointment
Sodium Citrate Tablets
Sorbitol Intravenous Infusion

General Monographs

General Monographs
The General Monographs for dosage forms are grouped together at the beginning of Volume III. They are followed by the monographs for the individual formulated preparations arranged in alphabetical order. The General Monographs of the European Pharmacopoeia apply to all individual dosage forms of the type defined rather than only to those preparations for which a specific monograph is included (see the General Notices).
Infrared Reference Spectra
To enable the user to locate a particular reference spectrum without difficulty, all have been assigned specific serial numbers within this edition. These are then cited within the text wherever reference to that spectrum is made.
Three new spectra have been added sequentially to the previous collection. A number of spectra that are no longer required have been removed from this edition.
Acknowledgements
The British Pharmacopoeia Commission is greatly indebted to the members of its advisory Committees and Consultative Groups without whose dedicated enthusiasm and assistance this edition could not have been prepared.
Close co-operation has continued with many organisations at home and overseas. These include the Medicines and Healthcare products Regulatory Agency (of which the Pharmacopoeia secretariat and laboratory staff are a part), the National Institute for Biological Standards and Control, the Veterinary Medicines Directorate, the Royal Pharmaceutical Society of Great Britain, the Association of the British Pharmaceutical Industry, the European Pharmacopoeia Commission and the European Directorate for the Quality of Medicines, the Therapeutic Goods Administration (Australia), the Health Protection Branch of the Canadian Department of Health and Welfare, the Committee of Revision of the United States Pharmacopeia, the Essential Drugs and Other Medicines Department of the World Health Organization (WHO) and the WHO Collaborating Centre for Chemical Reference Substances.
The British Pharmacopoeia Commission also acknowledges the advice of the publisher and the contribution made by Mr P Shaw, The Stationery Office, in the production of this edition which was published using the innovative ActiveTextTM software.

Storage

Storage
The General Notice on Storage included in Part II of the General Notices has been amended to specify that, unless otherwise stated in the monograph, the substances and preparations described in the British Pharmacopoeia are kept in well-closed containers and stored at a temperature not exceeding 25°. The monographs for medicinal substances and formulated preparations have therefore been amended to reflect the change in the General Notice.
European Pharmacopoeia
In accordance with previous practice, all monographs and requirements of the European Pharmacopoeia are reproduced in this edition of the British Pharmacopoeia or, where appropriate, within its companion edition, the British Pharmacopoeia (Veterinary).
Where a monograph has been reproduced from the European Pharmacopoeia this is signified by the presence of a European chaplet of stars alongside its title. Additionally, reference to the European Pharmacopoeia monograph number is included immediately below the title in italics in the form 'Ph Eur xxx'. Where the title in the British Pharmacopoeia is different from that in the European Pharmacopoeia, an approved synonym has been created (see Appendix XXI B) and a cross-reference to the Ph Eur title has been included in the Index. The entire European Pharmacopoeia text is then bounded by two horizontal lines bearing the symbol ¢Ph Eur¢.
The European Pharmacopoeia texts have been reproduced in their entirety without editorial modification but, where deemed appropriate, additional statements of relevance to UK usage have been added (e.g. action and use statement, a list of BP preparations). It should be noted, however, that in the event of doubt of interpretation in any text of the European Pharmacopoeia, the text published in English under the direction of the Council of Europe should be consulted.
Correspondence between the general methods of the European Pharmacopoeia and the appendices of the British Pharmacopoeia 2003 is indicated in each appendix and by inclusion of a check list at the beginning of the appendices section.
Pharmacopoeial Requirements
It should be noted that any article intended for medicinal use which is described by a name at the head of a monograph in the current edition of the Pharmacopoeia must comply with that monograph ¢whether or not it is referred to as BP¢.
It is also important to note that no requirement of the Pharmacopoeia can be taken in isolation. A valid interpretation of any particular requirement depends upon it being read in the context of (i) the monograph as a whole, (ii) the specified method of analysis, (iii) the relevant General Notices and (iv) where appropriate, the relevant general monograph. Familiarity with the General Notices of the Pharmacopoeia will facilitate the correct application of the requirements. Additional guidance and information on the basis of pharmacopoeial requirements is provided in Supplementary Chapter I. This non-mandatory text describes the general underlying philosophy and current approaches to particular aspects of pharmacopoeial control.

Introduction

Introduction
This edition of the British Pharmacopoeia supersedes the British Pharmacopoeia 2002. It has been prepared by the British Pharmacopoeia Commission with the collaboration and support of its advisory Committees and experts, and contains nearly 2900 monographs for substances and articles used in the practice of medicine. Some of these monographs are of national origin while others have been reproduced from the 4th edition of the European Pharmacopoeia. This new edition, together with its companion edition, the British Pharmacopoeia (Veterinary) 2003, contains all monographs of the 4th edition of the European Pharmacopoeia as amended by Supplements 4.1, 4.2, 4.3, 4.4 and 4.5. The user of the British Pharmacopoeia thereby benefits by finding within this one, comprehensively indexed, compendium all current United Kingdom pharmacopoeial standards for medicines for human use. The new edition comprises six volumes as follows:-
Effective Date
The effective date for this edition is 1st December 2003 unless otherwise stated.
Where a monograph which appeared previously in an earlier edition of the British Pharmacopoeia has not been included in this new edition, it remains effective in accordance with Section 65(4) of the Medicines Act 1968.
Additions
A list of monographs included within the Pharmacopoeia for the first time is given at the end of this introduction. It includes 12 new monographs of national origin and 68 new monographs reproduced from Supplements 4.3, 4.4 and 4.5 of the European Pharmacopoeia.
Revisions
National monographs which have been amended technically by means of this edition are also listed at the end of this introduction. For the benefit of the reader this list indicates the section, or sections, of each monograph which has/have been revised.
The list is as comprehensive as possible. However, to ensure that the reader uses the current standard it is essential to refer to the full text of each individual monograph.
Title changes
Monographs for medicinal substances and formulated preparations that were dual-labelled with both the recommended International Nonproprietary Name and the British Approved Name in the British Pharmacopoeia 2002 have been amended in this edition so that only the recommended International Nonproprietary Names are used. This is in accordance with the implementation of Directive 92/27/EEC. The two exceptions to the changes are Adrenaline and Noradrenaline for which the British Approved Names are retained. These are the names used in European Pharmacopoeia monographs and their associated formulation monographs. The changes are explained fully in Supplementary Chapter II A and the list of title changes is also included at the end of the Introduction. The list of Approved Synonyms has also been amended to reflect the changes. The former names used in the United Kingdom are included in a statement at the beginning of the relevant monograph for information.
The statement 'When [former title] is prescribed or demanded, [current title] shall be dispensed or supplied', previously included in monographs to provide continuity, has been deleted from monographs in this edition.
All those involved in the provision of medicines to the public are being alerted to the changes through an extensive communication strategy developed by the Medicines and Healthcare products Regulatory Agency and the Department of Health.

Formulated Preparations: Specific Monographs

Formulated Preparations: Specific Monographs
Cefradine Oral Suspension
Dexamethasone Sodium Phosphate Injection
Estradiol Transdermal Patches
Lacidipine Tablets
Levonorgestrel Tablets
Metronidazole Oral Suspension
Norgestrel Tablets
Potassium Dihydrogen Phosphate Concentrate, Sterile
Quinine Dihydrochloride Intravenous Infusion
Simeticone Suspension for Infants
Trimethoprim Oral Suspension
Immunological Products
Diphtheria, Tetanus and Hepatitis B (rDNA) Vaccine (Adsorbed)*
Diphtheria, Tetanus, Pertussis (Acellular Component), Poliomyelitis (Inactivated) and Haemophilus Type B Conjugate Vaccine (Adsorbed)*
Diphtheria, Tetanus, Pertussis and Poliomyelitis (Inactivated) Vaccine (Adsorbed)*
Diphtheria, Tetanus, Pertussis, Poliomyelitis (Inactivated) and Haemophilus Type B Conjugate Vaccine (Adsorbed)*
Radiopharmaceutical Preparations
Raclopride ([11C]Methoxy) Injection*
Sodium Acetate ([1-11C]) Injection*
Technetium (99mTc) Exametazime Injection*
Homoeopathic Preparations
Common Stinging Nettle for Homoeopathic Preparations*
Garlic for Homoeopathic Preparations*

Medicinal and Pharmaceutical Substances

Medicinal and Pharmaceutical Substances
Air, Synthetic*
Almagate*
Aminobenzoic Acid*
Basic Butylated Methacrylate Copolymer*
Bitter-fennel Fruit Oil*
Capsicum*
Cefapirin*
Cineole*
Clobazam*
Colophony*
Cresol, Crude*
Dihydrocodeine Tartrate*
Ebastine*
Econazole*
Erythritol*
Fish Oil, rich in Omega-3-acids*
Flubendazole*
Fluticasone Propionate*
Glucagon, Human*
Goserelin*
Hawthorn Leaf and Flower Dry Extract*
Knotgrass*
Lacidipine
Levomethadone Hydrochloride*
Linseed Oil, Virgin*
Magnesium Acetate Tetrahydrate*
Matricaria Oil*
Meadowsweet*
Mesalazine*
Methylpyrrolidone*
Motherwort*
Moxonidine*
Nicergoline*
Nicotine Resinate*
Nifuroxazide*
Nitrogen, Low-oxygen*
Omega-3-acid ethyl esters 60*
Ondansetron Hydrochloride Dihydrate*
Opium, Prepared*
Oregano*
Oxaliplatin*
Paraffin, White Soft*
Paroxetine Hydrochloride Hemihydrate*
Phenylmercuric Acetate*
Piracetam*
Plantain*
Potassium Clavulanate, Diluted*
Pravastatin Sodium*
Proguanil Hydrochloride*
Propanol*
Rhatany Tincture*
Rilmenidine Dihydrogen Phosphate*
Rutoside Trihydrate*
Saw Palmetto Fruit*
Sodium Glycerophosphate, Hydrated*
Sodium Propionate*
Squalane*
Tianeptine Sodium*
Wild Thyme*
Zinc Sulphate Hexahydrate*
* denotes a monograph of the European Pharmacopoeia

INTERNATIONAL SYSTEM OF UNITS (SI)

INTERNATIONAL SYSTEM OF UNITS (SI)
The International System of Units comprises three classes of units, namely base units, derived units and supplementary units1. The base units and their definitions are set out in Table 1.6-1.
The derived units may be formed by combining the base units according to the algebraic relationships linking the corresponding quantities. Some of these derived units have special names and symbols. The SI units used in the European Pharmacopoeia are shown in Table 1.6-2.
Some important and widely used units outside the International System are shown in Table 1.6-3.
The prefixes shown in Table 1.6-4 are used to form the names and symbols of the decimal multiples and submultiples of SI units.
NOTES
1. In the Pharmacopoeia the Celsius temperature is used (symbol t). This is defined by the equation
where T0 = 273.15 K by definition. The Celsius or centigrade temperature is expressed in degree Celsius (symbol °C). The unit "degree Celsius" is equal to the unit "kelvin".
2. The practical expressions of concentrations used in the Pharmacopoeia are defined in the General Notices.
3. The radian is the plane angle between two radii of a circle which cut off on the circumference an arc equal in length to the radius.
4. In the Pharmacopoeia conditions of centrifugation are defined by reference to the acceleration due to gravity (g):
5. Certain quantities without dimensions are used in the Pharmacopoeia: relative density (2.2.5), absorbance (2.2.25), specific absorbance (2.2.25) and refractive index (2.2.6).
6. The microkatal is defined as the enzymic activity which, under defined conditions, produces the transformation (e.g. hydrolysis) of 1 micromole of the substrate per second.
1 The definitions of the units used in the International System are given in the booklet "Le Système International d'Unités (SI)" published by the Bureau International des Poids et Mesures, Pavillon de Breteuil, F-92310 Sèvres.
Additions
The following monographs of the British Pharmacopoeia 2003 were not included in the British Pharmacopoeia 2002.

Abbreviations used in the monographs on immunoglobulins, immunosera and vaccines

Abbreviations used in the monographs on immunoglobulins, immunosera and vaccines
LD50 The statistically determined quantity of a substance that, when administered by the specified route, may be expected to cause the death of 50 per cent of the test animals within a given period
MLD Minimum lethal dose
L+/10 dose The smallest quantity of a toxin that, in the conditions of the test, when mixed with 0.1 IU of antitoxin and administered by the specified route, causes the death of the test animals within a given period
L+ dose The smallest quantity of a toxin that, in the conditions of the test, when mixed with 1 IU of antitoxin and administered by the specified route, causes the death of the test animals within a given period
lr/100 dose The smallest quantity of a toxin that, in the conditions of the test, when mixed with 0.01 IU of antitoxin and injected intracutaneously causes a characteristic reaction at the site of injection within a given period
Lp/10 dose The smallest quantity of toxin that, in the conditions of the test, when mixed with 0.1 IU of antitoxin and administered by the specified route, causes paralysis in the test animals within a given period
Lo/10 dose The largest quantity of a toxin that, in the conditions of the test, when mixed with 0.1 IU of antitoxin and administered by the specified route, does not cause symptoms of toxicity in the test animals within a given period
Lf dose The quantity of toxin or toxoid that flocculates in the shortest time with 1 IU of antitoxin
CCID50 The statistically determined quantity of virus that may be expected to infect 50 per cent of the cell cultures to which it is added
EID50 The statistically determined quantity of virus that may be expected to infect 50 per cent of fertilised eggs into which it is inoculated
ID50 The statistically determined quantity of a virus that may be expected to infect 50 per cent of the animals into which it is inoculated
PD50 The statistically determined dose of a vaccine that, in the conditions of the tests, may be expected to protect 50 per cent of the animals against a challenge dose of the micro-organisms or toxins against which it is active
ED50 The statistically determined dose of a vaccine that, in the conditions of the tests, may be expected to induce specific antibodies in 50 per cent of the animals for the relevant vaccine antigens
PFU Pock-forming units or plaque-forming units
SPF Specified-pathogen-free.

Biological Reference Preparation

Biological Reference Preparations
The majority of the primary biological reference preparations referred to in the European Pharmacopoeia are the appropriate International Standards and Reference Preparations established by the World Health Organisation. Because these reference materials are usually available only in limited quantities, the Commission has established Biological Reference Preparations (indicated by the abbreviation BRP) where appropriate. Where applicable, the potency of the Biological Reference Preparations is expressed in International Units. For some Biological Reference Preparations, where an international standard or reference preparation does not exist, the potency is expressed in European Pharmacopoeia Units.
Reference spectra
The reference spectrum is accompanied by information concerning the conditions used for sample preparation and recording the spectrum.
1.5. Abbreviations and symbols
A Absorbance
Specific absorbance
Ar Relative atomic mass
# Specific optical rotation
bp Boiling point
BRP Biological Reference Preparation
CRS Chemical Reference Substance
Relative density
IU International Unit
l Wavelength
M Molarity
Mr Relative molecular mass
mp Melting point
Refractive index
Ph. Eur. U. European Pharmacopoeia Unit
ppm Parts per million
R Substance or solution defined under Reagents
Rf Used in chromatography to indicate the ratio of the distance travelled by a substance to the distance travelled by the solvent front
Rst Used in chromatography to indicate the ratio of the distance travelled by a substance to the distance travelled by a reference substance
RV Substance used as a primary standard in volumetric analysis

REFERENCE SUBSTANCES, REFERENCE PREPARATIONS AND REFERENCE SPECTRA

REFERENCE SUBSTANCES, REFERENCE PREPARATIONS AND REFERENCE SPECTRA
Certain monographs require the use of a reference substance, a reference preparation or a reference spectrum. These are chosen with regard to their intended use as prescribed in the monographs of the Pharmacopoeia and are not necessarily suitable in other circumstances. The European Pharmacopoeia Commission does not accept responsibility for any errors arising from use other than as prescribed.
The reference substances, the reference preparations and the reference spectra are established by the European Pharmacopoeia Commission and may be obtained from the Technical Secretariat. They are the official reference materials to be used in cases of arbitration. A list of reference substances, reference preparations and reference spectra may be obtained from the Technical Secretariat.
Local reference materials may be used for routine analysis, provided they are calibrated against the materials established by the European Pharmacopoeia Commission.
Any information necessary for proper use of the reference substance or reference preparation is given on the label or in the accompanying leaflet or brochure. Where no drying conditions are stated in the leaflet or on the label, the substance is to be used as received. No certificate of analysis or other data not relevant to the prescribed use of the product are provided. No expiry date is indicated: the products are guaranteed to be suitable for use when despatched. The stability of the contents of opened containers cannot be guaranteed.
Chemical Reference Substances
The abbreviation CRS indicates a Chemical Reference Substance established by the European Pharmacopoeia Commission. Some Chemical Reference Substances are used for the microbiological assay of antibiotics and their activity is stated, in International Units, on the label or on the accompanying leaflet and defined in the same manner as for Biological Reference Preparations.

LABELLING

LABELLING
In general, labelling of medicines is subject to supranational and national regulation and to international agreements. The statements under the heading Labelling therefore are not comprehensive and, moreover, for the purposes of the Pharmacopoeia only those statements that are necessary to demonstrate compliance or non-compliance with the monograph are mandatory. Any other labelling statements are included as recommendations. When the term "label" is used in the Pharmacopoeia, the labelling statements may appear on the container, the package or a leaflet accompanying the package, as decided by the competent authority.
WARNINGS
Materials described in monographs and reagents specified for use in the Pharmacopoeia may be injurious to health unless adequate precautions are taken. The principles of good quality control laboratory practice and the provisions of any appropriate regulations are to be observed at all times. Attention is drawn to particular hazards in certain monographs by means of a warning statement; absence of such a statement is not to be taken to mean that no hazard exists.
IMPURITIES
A list of all known and potential impurities that have been shown to be controlled by the tests in a monograph may be given for information. The list may be divided into two sublists entitled "Qualified impurities" and "Other detectable impurities". Qualified impurities are those previously accepted by the competent authority as being qualified; impurities deemed qualified by other means (for example, impurities which occur as natural metabolites) may also be included. Other detectable impurities are those potential impurities that have not been detected in any samples of the substance during elaboration of the monograph or that occur in amounts below 0.1 per cent, but that have been shown to be limited by the tests.
FUNCTIONALITY-RELATED CHARACTERISTICS
A list of functionality-related characteristics that are not the subject of official requirements but which are nevertheless important for the use of a substance may be appended to a monograph, for information (see also above 1.1. General statements).

Collections of micro-organisms

Collections of micro-organisms
ATCC American Type Culture Collection
10801 University Boulevard
Manassas, Virginia 20110-2209, USA
C.I.P Collection de Bactéries de l'Institut Pasteur
B.P. 52, 25 rue du Docteur Roux
75724 Paris Cedex 15, France
IMI International Mycological Institute
Bakeham Lane
Surrey TW20 9TY, Great Britain
I.P. Collection Nationale de Culture de Microorganismes (C.N.C.M.)
Institut Pasteur
25, rue du Docteur Roux
75724 Paris Cedex 15, France
NCIMB National Collection of Industrial and Marine Bacteria Ltd
23 St Machar Drive
Aberdeen AB2 1RY, Great Britain
NCPF National Collection of Pathogenic Fungi
London School of Hygiene and Tropical Medicine
Keppel Street
London WC1E 7HT, Great Britain
NCTC National Collection of Type Cultures
Central Public Health Laboratory
Colindale Avenue
London NW9 5HT, Great Britain
NCYC National Collection of Yeast Cultures
AFRC Food Research Institute
Colney Lane
Norwich NR4 7UA, Great Britain
S.S.I. Statens Serum Institut
80 Amager Boulevard, Copenhagen, Denmark

Indication of permitted limit of impurities

Indication of permitted limit of impurities
For comparative tests, the approximate content of impurity tolerated, or the sum of impurities, may be indicated for information only. Acceptance or rejection is determined on the basis of compliance or non-compliance with the stated test. If the use of a reference substance for the named impurity is not prescribed, this content may be expressed as a nominal concentration of the substance used to prepare the reference solution specified in the monograph, unless otherwise described.
Vegetable drugs
For vegetable drugs, the sulphated ash, total ash, water-soluble matter, alcohol-soluble matter, water content, content of essential oil and content of active principle are calculated with reference to the drug that has not been specially dried, unless otherwise prescribed in the monograph.
Equivalents
Where an equivalent is given, for the purposes of the Pharmacopoeia only the figures shown are to be used in applying the requirements of the monograph.
STORAGE
The information and recommendations given under the heading Storage do not constitute a pharmacopoeial requirement but the competent authority may specify particular storage conditions that must be met.
The articles described in the Pharmacopoeia are stored in such a way as to prevent contamination and, as far as possible, deterioration. Where special conditions of storage are recommended, including the type of container (see 1.3. General chapters) and limits of temperature, they are stated in the monograph.
The following expressions are used in monographs under Storage with the meaning shown.
In an airtight containermeans that the product is stored in an airtight container(3.2). Care is to be taken when the container is opened in a damp atmosphere. A low moisture content may be maintained, if necessary, by the use of a desiccant in the container provided that direct contact with the product is avoided.
Protected from light means that the product is stored either in a container made of a material that absorbs actinic light sufficiently to protect the contents from change induced by such light or in a container enclosed in an outer cover that provides such protection or stored in a place from which all such light is excluded.

CHARACTERS

CHARACTERS
The statements under the heading Characters are not to be interpreted in a strict sense and are not requirements.
Solubility
In statements of solubility in the section headed Characters, the terms used have the following significance referred to a temperature between 15 °C and 25 °C.
The term "partly soluble" is used to describe a mixture where only some of the components dissolve. The term "miscible" is used to describe a liquid that is miscible in all proportions with the stated solvent.
IDENTIFICATION
The tests given in the identification section are not designed to give a full confirmation of the chemical structure or composition of the product; they are intended to give confirmation, with an acceptable degree of assurance, that the article conforms to the description on the label.
Certain monographs have subdivisions entitled "First identification" and "Second identification". The test or tests that constitute the "Second identification" may be used instead of the test or tests of the "First identification" provided it can be demonstrated that the substance or preparation is fully traceable to a batch certified to comply with all the requirements of the monograph.
TESTS AND ASSAYS
Scope
The requirements are not framed to take account of all possible impurities. It is not to be presumed, for example, that an impurity that is not detectable by means of the prescribed tests is tolerated if common sense and good pharmaceutical practice require that it be absent. See also below under Impurities.
Calculation
Where the result of a test or assay is required to be calculated with reference to the dried or anhydrous substance or on some other specified basis, the determination of loss on drying, water content or other property is carried out by the method prescribed in the relevant test in the monograph. The words "dried substance" or "anhydrous substance", etc. appear in parenthesis after the result.
Limits
The limits prescribed are based on data obtained in normal analytical practice; they take account of normal analytical errors, of acceptable variations in manufacture and compounding and of deterioration to an extent considered acceptable. No further tolerances are to be applied to the limits prescribed to determine whether the article being examined complies with the requirements of the monograph.
In determining compliance with a numerical limit, the calculated result of a test or assay is first rounded to the number of significant figures stated, unless otherwise prescribed. The last figure is increased by one when the part rejected is equal to or exceeds one half-unit, whereas it is not modified when the part rejected is less than a half-unit.

PRODUCTION

Statements under the heading Production draw attention to particular aspects of the manufacturing process but are not necessarily comprehensive. They constitute instructions to manufacturers. They may relate, for example, to source materials, to the manufacturing process itself and its validation and control, to in-process testing or to testing that is to be carried out by the manufacturer on the final article either on selected batches or on each batch prior to release. These statements cannot necessarily be verified on a sample of the final article by an independent analyst. The competent authority may establish that the instructions have been followed, for example, by examination of data received from the manufacturer, by inspection of manufacture or by testing appropriate samples.
The absence of a section on Production does not imply that attention to features such as those referred to above is not required. A product described in a monograph of the Pharmacopoeia is manufactured in accordance with a suitable quality system in accordance with relevant international agreements and supranational and national regulations governing medicinal products for human or veterinary use.
Where in the section under the heading Production a monograph on a vaccine defines the characteristics of the vaccine strain to be used, any test methods given for confirming these characteristics are provided for information as examples of suitable methods.

Materials used for containers are described in general chapter 3. General names used for materials, particularly plastics materials, each cover a range of products varying not only in the properties of the principal constituent but also in the additives used. The test methods and limits for materials depend on the formulation and are therefore applicable only for materials whose formulation is covered by the preamble to the specification. The use of materials with different formulations and the test methods and limits applied to them are subject to agreement by the competent authority.
The specifications for containers in general chapter 3 have been developed for general application to containers of the stated category but in view of the wide variety of containers available and possible new developments, the publication of a specification does not exclude the use, in justified circumstances, of containers that comply with other specifications, subject to agreement by the competent authority.
Reference may be made within the monographs of the Pharmacopoeia to the definitions and specifications for containers provided in this section. The general monographs for pharmaceutical dosage forms may, under the heading Definition/Production, require the use of certain types of container; certain other monographs may, under the heading Storage, indicate the type of container that is recommended for use.

TEMPERATURE

TEMPERATURE
Where an analytical procedure describes temperature without a figure, the general terms used have the following meaning:
In a deep-freeze: below - 15 °C
In a refrigerator: 2 °C to 8 °C
Cold or cool: 8 °C to 15 °C
Room temperature: 15 °C to 25 °C

EXPRESSION OF CONTENT

In defining content, the expression "per cent" is used according to circumstances with one of two meanings:
per cent m/m (percentage, mass in mass) expresses the number of grams of substance in 100 grams of final product.
per cent V/V (percentage, volume in volume) expresses the number of millilitres of substance in 100 millilitres of final product.
The expression "parts per million (ppm)" refers to mass in mass, unless otherwise specified.

SOLVENTS

SOLVENTS
Where the name of the solvent is not stated, the term "solution" implies a solution in water.
Where the use of water is specified or implied in the analytical procedures described in the Pharmacopoeia or for the preparation of reagents, water complying with the requirements of the monograph on Purified water (0008) is used. The term "distilled water" indicates purified water prepared by distillation.
The term "ethanol" without qualification means anhydrous ethanol. The term "alcohol" without qualification means ethanol (96 per cent V/V). Other dilutions of ethanol are indicated by the term "alcohol" followed by a statement of the percentage by volume of ethanol (C2H6O) required.

REAGENTS

REAGENTS
The proper conduct of the analytical procedures described in the Pharmacopoeia and the reliability of the results depend, in part, upon the quality of the reagents used. The reagents are described in general chapter 4. It is assumed that reagents of analytical grade are used; for some reagents, tests to determine suitability are included in the specifications.