สารบัญ

      The main objective of the Thai Pharmacopoeia is to establish the Thai National Standards of selected pharmaceutical substances and preparations. Apart from their standards and requirements set forth in the monographs, the non-mandatory information given includes their main classes of actions and applications (categories) and their safety (contra-indications, warnings, etc.). Subjected to other pertinent laws and ministerial regulations and notifications promulgated by Thai Minister of Public Health, the various standards of articles set up in this book, together with their pharmacopoeial requirements, are legally recognized by the Royal Thai Government.
      The General Notices and general requirements appearing in appendices provide the basic guidelines for the interpretation and application of the standards, tests, assays, and other specifications of the Pharmacopoeia. Where exceptions to the General Notices or Appendices are made, the expressions such as “unless otherwise specified”, “unless otherwise directed”, or “unless otherwise indicated” are employed.

TITLE

      The full title of this book, including its supplements, is the Pharmacopoeia of the Kingdom of Thailand, second edition. This title may be abbreviated to Thai Pharmacopoeia, second edition, or to TP II. Where the term TP is used, without further qualification, during the period in which this Pharmacopoeia is officially effective, it refers to TP II.

“Official”, “Official Name” and “Official Standards”

     The word “official”, as used in this Pharmacopoeia or with reference hereto, is synonymous with “Pharmacopoeial”, with “TP”, and with  compendial”.
     The “official name” implies the “main title” of each Pharmacopoeial substance or preparation which is given in English and printed with capital letters. Any other names or subsidiary titles, where included, have the same status as the main title. They are mostly derived from the main title of that substance or preparation as they are used in the National List of Essential Medicine and the other recognized pharmacopoeiae such as the International Pharmacopoeia, the British Pharmacopoeia, and the United States Pharmacopeia. In some cases, the spelling “sulph-” may be substituted for “sulf-” in the main title. Similarly, the spelling “aluminum” may also be substituted for “aluminium”.
      For crude drugs, Thai names are also included and transcribed into English following the Royal Institute’s official transliteration system. Subsidiary titles for crude drugs are their most commonly recognized English names.
      In a monograph of pharmaceutical preparations, “other names” or “subsidiary titles” is nevertheless excluded.
      The terminology “article” is an item for which a monograph is provided, whether a substance or a preparation.
      The requirements stated in the monographs of the Pharmacopoeia apply to articles that are intended only for medicinal use. An article intended or labelled for medicinal use that is described by means of an official title must comply with the requirements of the relevant monograph. A formulated preparation must comply throughout its assigned shelf-life (period of validity). The subject of any other monograph must comply throughout its period of use.
       Unless otherwise indicated in the General Notices or in the monographs, statements in monographs constitute mandatory requirements. The chemical formula and solubility statements are presented for informative purposes only and are not to be considered in the same category as the standards or tests for purity. The tests or methods in general appendices become mandatory when referred to in a monograph, unless such reference is made in a way to indicate that it is not the intention to make the text referred to
mandatory but rather to cite it for information.
       An article is not of pharmacopoeial quality unless it complies with all of the requirements stated. The general notice on Assays and Tests indicates that analytical methods other than those described in the Pharmacopoeia may be employed for routine purposes.
       Where a monograph on a biological substance or preparation refers to a strain, a test, a method, a substance, etc., using the qualifications “suitable” or “appropriate” without further definition in the text, the choice of such strain, test, method, substance, etc., is made in accordance with any international agreements or national regulations affecting the subject concerned.
       The designation “TP” in conjunction with the official title or elsewhere on the label of article indicates that a monograph is included in the Thai Pharmacopoeia and that the article must comply with all applicable TP standards.

Printing Types

        In the text, words which refer to reagents, which conform to the requirements specified in the appendices of other parts of the book, and the systematic names of plants, animals and micro-organisms are usually printed in italics to distinguish them from the other words in that portion of the text.

Significant Figures and Tolerances

        Where limits are expressed numerically herein, the upper and lower limits of a range include the two values themselves and all intermediate values, but no values outside the limits. The limits expressed in monograph definitions and tests, regardless of whether the values are expressed as percentages or as absolute numbers, are considered significant to the last digit shown.

EQUIVALENCE STATEMENTS IN TITRIMETRIC PROCEDURES In the equivalence statement of titrimetric procedures, the number of significant figures in the concentration of the titrant corresponds to the number of significant figures in the weight of the analyte.

TOLERANCES The limits specified in the monographs for Pharmacopoeial articles are established with a view to the use of these articles as drugs, except where it is indicated otherwise. The use of the molecular formula for the active ingredient(s) named in defining the required strength of a Pharmacopoeial article is intended to designate the chemical entity or entities, as given in the complete chemical name of the article, having absolute (100 per cent) purity.
        A dosage form shall be formulated with the intent to provide 100 per cent of the quantity of each ingredient declared on the label. The tolerances and limits stated in the Definitions in the monographs for Pharmacopoeial articles allow for analytical error, for unavoidable variations in manufacturing and compounding, and for deterioration to an extent considered acceptable under practical conditions. No further tolerances should be applied to the values obtained in an assay to determine whether the product
being examined complies with the requirements of monograph.
        The specified tolerances are based upon such attributes of quality as might be expected to characterize an article produced from suitable raw materials under recognized principles of good manufacturing practice.

INTERPRETATION OF REQUIREMENTS Analytical results in the laboratory (observed or calculated from experimental measurements) are compared with stated limits to determine whether there is conformance with compendial assay or test requirements. The observed or calculated values usually will contain more significant figures than there are in the stated limit, and a reportable result is to be rounded off to the number of places that is in agreement with the limit expression by the following procedure. Intermediate calculations (e.g., slope for linearity in validation of compendial method) may be rounded for reporting purposes, but the original value (not rounded) should be used for any additional required calculations. Rounding off should not be done until the final calculations for the reportable value have been completed. (Note Limits, which are fixed numbers, are not rounded off.) When rounding off is required, consider only one digit in the decimal place to the right of the last place in the limit expression. If this digit is smaller than 5, it is eliminated and the preceding digit is unchanged. If this digit is equal to 5 or more than 5, it is eliminated and the preceding digit is increased by one.

Illustration of Rounding Numerical Values for Comparison with Requirements

Compendial Requirement	Unrounded Value		Rounded Result		Conforms
Assay limit ≥ 99.0 per cent	98.97	per cent	99.0	per cent	Yes
	98.93	per cent	98.9	per cent	No
	98.95	per cent	99.0	per cent	Yes
Assay limit ≤ 102.5 per cent	102.55	per cent	102.6	per cent	No
	102.54	per cent	102.5	per cent	Yes
	102.56	per cent	102.6	per cent	No
Limit test ≤0.03 per cent	0.035	per cent	0.04	per cent	No
	0.034	per cent	0.03	per cent	Yes
	0.037	per cent	0.04	per cent	No
Limit test ≤2 ppm	2.4	ppm	2	ppm	Yes
	2.5	ppm	3	ppm	No
	2.6	ppm	3	ppm	No

 

Limit of Content

       When limits of content are prescribed in a monograph, they are determined by the method described under “Assay”.
       When the result of a test or assay is referred to the “dried”, “anhydrous” or “ignited” substance, the determination of loss on drying, water content or loss on ignition is carried out by the method prescribed under the heading “Loss on drying”, “Water” or “Loss on ignition”, respectively, in the monograph concerned.

Freshly and Recently Prepared

        The direction that a preparation must be freshly prepared indicates that it must be made not more than 24 hours before it is issued for use. The direction that a preparation should be recently prepared indicates that deterioration is likely if the preparation is stored for longer than about 4 weeks at 15º to 25º.

Added Substances

        The word “added substances” as used in this Pharmacopoeia or with reference hereto is synonymous with “auxiliary substances”.
         An official substance, as distinguished from an official preparation, contains no added substances except where specifically permitted in the individual monograph. Where such addition is permitted, the label indicates the name(s) and amount(s) of any added substance(s).
         Unless otherwise specified in the individual monograph, or elsewhere in the General Notices, suitable substances such as antimicrobial agents, bases, carriers, coatings, colours, flavours, preservatives, stabilizers, and vehicles may be added to an official preparation to enhance its stability, usefulness, or elegance or to facilitate its preparation. Such substances are regarded as unsuitable and are prohibited unless (a) they are harmless in the amounts used, (b) they do not exceed the minimum quantity required to provide their intended effect, (c) their presence does not impair the bioavailability or the therapeutic efficacy or safety of the official preparation, and (d) they do not interfere with the assays and tests prescribed for determining compliance with the Pharmacopoeial standards.

Colouring Agents

         Added substances employed solely to impart colour may be incorporated into official preparations, except those intended for parenteral or ophthalmic use, in accordance with the regulations pertaining to the use of colouring agents issued by the Thai Food and Drug Administration provided such added substances are otherwise appropriate in all respects

Description

         Information on the “description” pertaining to an article, which is relatively general in nature, is provided for those who use, prepare, and dispense drugs, solely to indicate the properties of an article complying with monograph standards. The properties are not in themselves standards or tests for purity even though they may indirectly assist in the preliminary evaluation of the integrity of an article.
         In the case of crude drugs, the macroscopical description of a drug includes those features which can be seen by the unaided eye or by the use of a hand lens. The diagnostic characters given under a powdered crude drug are to be read in conjunction with the microscopical description given under the whole drug.
         Statements of the distinctive microscopic structural elements in powdered crude drugs may be included in the individual monograph as a means of determining identity, quality, or purity.

Solubility

         Statements given in the monographs under “Solubility” are intended as information on the approximate solubility only and are not regarded as part of the standard for a substance. Where no temperature is given,
statements of solubility apply at ordinary room temperature.
         Statements given under “Solubility test” express exact requirements and constitute part of the standards for the substances under which they occur.
         When the term “parts” is used in expressing the solubility of a substance, it means parts by weight (grams) of a solid in parts by volume (millilitres) of the solvent, or parts by volume (millilitres) of a liquid in parts by volume (millilitres) of the solvent. The following table indicates the meanings of such terms:

Descriptive Term	Parts of Solvent Required for 1 Part of Solute
Very soluble	less than 1
Free soluble	from 1 to 10
Soluble	from 10 to 30
Sparingly soluble	from 30 to 100
Slightly soluble	from 100 to 1000
Very slightly soluble	from 1000 to 10,000
Practically insoluble or insoluble	more than 10,000

 

Category

        A statement of Category usually is provided for each pharmacopoeial substance. This indicates the class of its main pharmacological action and its application. Where there are several main actions or applications, usually not more than the two most important are selected, with due consideration to the prevailing medical situation. No attempt has been made to describe in detail the actions and uses of a drug nor to specify its indications. The statement of Category is thus not intended to limit in any way the choice or use of the drug nor to indicate that it has no other activity or utility.

Strength(s) Available

           Statements under the side-headings Strength or Strengths Available are included as a guide and are not necessarily comprehensive. For solid dosage forms such as Capsules and Tablets, the strength is given as the amount of active ingredient in each unit. For liquid dosage forms such as Injections and semi-solid dosage forms such as Creams, the strength is given as a concentration. For Powders for Injections, the strength is given as the amount of active ingredient in each sealed container. Unless otherwise stated, the strength is given in terms of the weight or concentration of the official medicinal substance used in making the formulation.

Dose

        The statements given under “Dose” in the monographs of the Pharmacopoeia are primarily intended to serve only as a guide to physicians or pharmacists who may vary it in the best interests of patients and in accordance with the variables that affect the action of the drug

The specific terms used to classify the age of the patients are as follows:

- Adults: over 12 years of age
- Adolescents: 12 to 15 years of age
- Children: 1 to 12 years of age
- Infants: 5 weeks to 1 year of age
- Neonates: from newborn to 1 month of age

           Unless otherwise specified, the route of administration is oral.
           The statements of dosage in the case of Capsules and Tablets are expressed in terms of the content of active ingredient and seldom represent the total weight of the capsule contents or of the tablets.
           In some instances, the dosage may be stated in terms of the pharmacologically active portion (moiety) of the molecule in order to permit the prescriber or dispenser to correlate the weight equivalent for salts, esters, or other chemical forms of the same drug moiety. However, it is not to be inferred that all chemical forms in which the active moiety may be presented are therapeutically equivalent.
           Where the body surface area is stated as a basis for the specified dose, the “Table of Body Surface Area from Height and Weight (m2)” in Appendix 1.17 may be employed to simplify the calculation of square
metres of body surface.
           The dose given in each monograph is that which may ordinarily be expected to produce in the patients with normal renal/hepatic function, following administration in the manner indicated, at such time intervals as may be stated, the diagnostic, therapeutic or prophylactic effect for which the monograph is recognized.

Other Relevant Information

          The statements under “Other Relevant Information” provide information that does not constitute standards, but enable better understanding of the drug. This includes, but not limited to, safety information such as contra-indications, warnings and precautions; specific routes of administration to be used for a particular drug; any pertinent personal observation or care for specific patient groups, and other related information such as stability data. Selection of information is based on what is considered practical and significant in an effective and safe use of a drug, minimizing risks and maximizing benefits from its use.

Packaging and Storage

          The substances and preparations described in the Pharmacopoeia are stored in such a way as to prevent contamination and, as far as possible, deterioration. Precautions that should be taken in relation to the effects of the atmosphere, moisture, heat, and light are indicated, where appropriate, in the monographs.

          CONTAINERS
          The container is the device that holds the substance, either in the form of the raw material or of the finished dosage form. The closure of the container, including the stopper, the cap, the attached dropper, etc., is considered as a part of the container.
          The immediate container is the one which is in direct contact with the substance.
          The container should be cleaned before use, and no extraneous matter should be introduced into it or into the substance placed in it. It must, likewise, not interact physically or chemically with the substance which it holds so as to alter the latter’s quality, purity, or therapeutic potency to a level below its Pharmacopoeial requirements.

          Well-closed container 
          A well-closed container must protect the contents from extraneous matter or from loss of the substance under ordinary or customary conditions of handling, shipment, storage, or sale.

          Tightly closed container 
           A tightly closed container must protect the contents from contamination by extraneous matter or moisture, from loss of the substance, and from efflorescence, deliquescence, or evaporation under the ordinary or customary conditions of handling, shipment, storage, or sale, and shall be capable of tight reclosure. Where a tightly closed container is specified, it may be replaced by a hermetically closed container for a single-dose of the substance.

          Hermetically closed container 
          A hermetically closed container must be impervious to air or any other gas under the ordinary customary conditions of handling, shipment, storage, or sale.

          Light-resistant container 
          A light-resistant container is the one which prevents transmission of light, such as an opaque container or a bottle of black, dark red or dark brown glass.

          STORAGE
          The following expressions are used in monographs under Packaging and storage with the meaning shown.

          Protected from light means that the product is to be stored either in a light-resistant container 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.

          STORAGE TEMPERATURES
          When special conditions of storage are necessary, including limits of temperature, they are prescribed in the monograph. Where, in a monograph, the storage conditions are mentioned using the general expressions “at room temperature”, “in a cold place”, and the like, these terms are generally defined as follows.

Very cold temperature Any temperature above –10º but not higher than 8º. A refrigerator is a very coldplace in which the temperature is maintained thermostatically between 2º and 8º.
Cold temperature Any temperature above 8º but not higher than 16º.
Cool temperature Any temperature above 16º but not higher than 23º.
Room temperature Any temperature above 23º but not higher than 35º.

Labelling

          Every article in this Pharmacopoeia shall bear one or more labels indicating its identity and certain pertinent characteristics. This label(s) shall be affixed or firmly fastened to, or indelibly written on, the article’s immediate container and, if any, its package. The label shall comply, in addition to the requirements prescribed in the Pharmacopoeia, with those labelling requirements currently promulgated by the Thai Ministry of Public Health. In cases where contradiction might arise between these requirements the latter
bears more legal authority.
          A shipping container, or a shipping package, unless such container or package is also essentially the immediate container or the outside of the consumer package, is exempt from the labelling requirements of this Pharmacopoeia.
          Labelling requirements, also, do not necessarily apply when the article is supplied in compliance with a medical prescription.
          The label on the container and the label on the package of every official article state:
          (1) the name (commercial and/or generic) of the article, together with its dosage form;
          (2) for herbal drugs and herbal drug preparations, where applicable, the Latin binomial and, following the official name, the part of the plant source from which the article was derived;
          (3) the name and address of the manufacturer;
          (4) amount(s) of active ingredient(s) per dosage unit (capsule, tablet, or other unit dosage form), per gram (or 100 grams), per millilitre (or 100 millilitres), or per other measurement, as the case may be;
          (5) total amount of the article in the immediate container;
          (6) batch or lot, or quality control, number or code of the product;
          (7) the expiration date;
          (8) where applicable, the name(s) of any antimicrobial preservative(s);
          (9) for herbal drug preparations, “Consult a physician or pharmacist prior to use if you are pregnant or breastfeeding”;
         (10) other statements specifically required under “Labelling” in that article’s monograph.
         Where an expiration date is required to be stated on the label, this date identifies the time during which the article may be expected to meet the requirements of the Pharmacopoeial monograph, provided it is kept under the prescribed storage conditions. The expiration date limits the time during which the product may be dispensed or used. Where an expiration date is stated only in terms of the month and the year, it is a representation that the intended expiration date is the last day of the stated month. For articles requiring constitution prior to use, a suitable beyond-use date for the constituted product shall be identified on the label. The beyond-use date placed on the label shall not be later than the expiration date on the manufacturer’s container.

Identification

          Identification tests are provided for the verification of the identity of the substance described in the monograph. A judgment by the analyst is needed as to the extent of testing required, taking into account the available instrumentation.
          It is generally recognized that the infrared spectrum provides the best method of identification because of the uniqueness of a well-developed “fingerprint” region of the spectrum for a given drug substance.
          Wherever possible, infrared spectrum characteristics are used as the primary test of identification. Usually this can stand by itself without any additional test. However, where the article is a salt, it is necessary to include a “specific ion test”. Further identification tests provided in an individual monograph, taken together, are intended to provide verification of identity, should the use of an infrared spectrophotometer be precluded. Such identification tests, however specific, are not necessarily sufficient to establish proof of
identity; but failure of an article taken from a labelled container to meet the requirements of a prescribed identification test indicates that the article may be mislabelled. Other tests and specifications in the monograph often contribute to establishing or confirming the identity of the article under examination.
          It should further be noted that whenever a melting temperature is provided under the heading “Identification”, an approximate value is usually given, since no exact reproduction of the quoted temperature is necessary.

Arsenic and Heavy Metals

          With regard to vegetable drugs, the toxic elements which may be present in sufficient quantity to pose potential risk vary from plant to plant. The amount of these elements depends on the location, the quality of the soil, or environmental pollution. Because of their toxic natures, arsenic and heavy metals are of major concern. Although not specifically required in the monograph, it is suggested that the maximum amounts of the toxic elements, based on the acceptable daily intake (ADI) values, in final dosage forms of plant materials be as follows:

Arsenic	4	ppm
Cadmium	0.3	ppm
Lead	10	ppm
Mercury	0.5	ppm

 

          Unless otherwise indicated, the test procedures are provided in the “Limit Tests for Heavy Metals in Herbal Drugs and Herbal Drug Preparations” (Appendix 5.2).

Microbial Contamination

          Although not specifically required in the monographs, possible microbial contamination should be controlled to such an extent that the preparations derived from them meet the requirements as described in the “Limits for Microbial Contamination” (Appendix 10.5).

Water and Loss on Drying

          Where the water of hydration or adsorbed water of a Pharmacopoeial article is determined by the titrimetric method, the test is generally given under the heading “Water”. Where the determination is made by drying under specified conditions, the test is generally given under the heading “Loss on drying”. However, “Loss on drying” is most often given as the heading where the loss in weight is known to represent residual volatile constituents including organic solvents as well as water.

Assays and Tests

          The Assays and Tests described are the official methods upon which the standards of the Pharmacopoeia depend. Assay and test procedures are provided for determining compliance with the Pharmacopoeial standards of identity, strength, quality and purity. The analysts are not precluded from employing alternative methods, including methods of micro-analysis, in any Assay or Test if they are satisfied that the method which they use will give the results of equivalent accuracy. In the event of doubt or dispute, the methods of analysis described in the Pharmacopoeia alone are authoritative.
          When the solvent used for a solution is not named, the solvent is Purified Water.
          The use of a proprietary designation to identify a material used in an Assay or Test does not imply that another equally suitable material may not be used.

          APPARATUS
          A specification for a definite size or type of container or apparatus in a test or assay is given solely as a recommendation. Where volumetric flasks or other exact measuring, weighing, or sorting devices are specified, this or other equipment of at least equivalent accuracy shall be employed. Where low-actinic or light-resistant containers are specified, clear containers that have been rendered opaque by application of a suitable coating or wrapping may be used.
          Where an instrument for physical measurement, such as a spectrophotometer, is specified in a test or assay by its distinctive name, another instrument of equivalent or greater sensitivity and accuracy may be used. In order to obtain solutions having concentrations that are adaptable to the working range of the instrument being used, solutions of proportionately higher or lower concentrations may be prepared according to the solvents and proportions thereof that are specified for the procedure. Where a particular
brand or source of a material, instrument, or piece of equipment, or the name and address of a manufacturer or distributor, is mentioned, this identification is furnished solely for informational purposes as a matter of convenience, without implication of approval, endorsement, or certification. Items capable of equal or better performance may be used if these characteristics have been validated.
          Where the use of a centrifuge is indicated, unless otherwise specified, the directions are predicated upon the use of apparatus having an effective radius of about 20 cm (8 inches) and driven at a speed sufficient to clarify the supernatant layer within 15 minutes.
          Unless otherwise specified, for chromatographic tubes and columns the diameter specified refers to internal diameter; for other types of tubes and tubing the diameter specified refers to outside diameter.
          While one of the primary objectives of the Pharmacopoeia is to assure the user of official articles of their identity, strength, quality, and purity, it is manifestly impossible to include in each monograph a test for every impurity, contaminant, or adulterant that might be present, including microbial contamination. These may arise from a change in the source of material or from a change in the processing, or may be introduced from extraneous sources. Tests suitable for detecting such occurrences, the presence of which is inconsistent with applicable good manufacturing practice or good pharmaceutical practice, should be employed in addition to the tests provided in the individual monograph.

          PROCEDURE
          In performing the assay or test procedures in this Pharmacopoeia, it is expected that safe laboratory practices will be followed. This includes the use of precautionary measures, protective equipment, and work practices consistent with the chemicals and procedures used. Prior to undertaking any assay or procedure described in this Pharmacopoeia, the individual should be aware of the hazards associated with the chemicals and the procedures and means of protecting against them. This Pharmacopoeia is not
designed to describe such hazards or protective measures.
          Automated procedures employing the same basic chemistry as those assay and test procedures given in the monograph are recognized as being equivalent in their suitability for determining compliance. Conversely, where an automated procedure is given in the monograph, manual procedures employing the same basic chemistry are recognized as being equivalent in their suitability for determining compliance.
          In the performance of assay or test procedures, not less than the specified number of dosage units should be taken for analysis. Proportionately larger or smaller quantities than the specified weights and volumes of assay or test substances and Reference Standards may be taken, provided the measurement is made with at least equivalent accuracy and provided that any subsequent steps, such as dilutions, are adjusted accordingly to yield concentrations equivalent to those specified and are made in such manner as to provide at least equivalent accuracy. To minimize environmental impact or contact with hazardous materials, apparatus and chemicals specified in Pharmacopoeial procedures also may be proportionally changed.
          Where it is directed in an assay or a test that a certain quantity of substance or a counted number of dosage units is to be examined, the specified quantity or number is a minimal figure (the singlet determination) chosen only for convenience of analytical manipulation; it is not intended to restrict the total quantity of substance or number of units that may be subjected to the assay or test or that should be tested in accordance with good manufacturing practices.
          Where it is directed in the assay of Tablets to “weigh and finely powder not less than” a given number, usually 20, of the Tablets, it is intended that a counted number of Tablets shall be weighed and reduced to a powder. The portion of the powdered tablets taken for assay is representative of the whole Tablets and is, in turn, weighed accurately. The result of the assay is then related to the amount of active ingredient per Tablet by multiplying this result by the average Tablet weight and dividing by the weight of the portion taken forthe assay.
          Similarly, where it is directed in the assay of Capsules to remove, as completely as possible, the contents of not less than a given number, usually 20, of the Capsules, it is intended that a counted number of Capsules should be carefully opened and the contents quantitatively removed, combined, mixed, and weighed accurately. The portion of mixed Capsules contents taken for the assay is representative of the contents of the Capsules and is, in turn, weighed accurately. The result of the assay is then related to the
amount of active ingredient per Capsule by multiplying this result by the average weight of Capsule content and dividing by the weight of the portion taken for the assay.
          Where the definition in a monograph states the tolerances as being “calculated on the dried (or anhydrous or ignited) basis,” the directions for drying or igniting the sample prior to assaying are generally omitted from the Assay procedure. Assay and test procedures may be performed on the undried or unignited substance and the results calculated on the dried, anhydrous, or ignited basis, provided a test for Loss on drying, or Water, or Loss on ignition, respectively, is given in the monograph. Results are calculated on an “as-is” basis unless otherwise specified in the monograph. Where the presence of moisture or other volatile material may interfere with the procedure, previous drying of the substance is specified in the individual monograph and is obligatory.
          Throughout a monograph that includes a test for Loss on drying or Water, the expression “previously dried” without qualification signifies that the substance is to be dried as directed under Loss on drying or Water (gravimetric determination).
          In stating the appropriate quantities to be taken for assays and tests, the use of the word “about” indicates a quantity within 10 per cent of the specified weight or volume. However, the weight or volume taken is accurately determined, and the calculated result is based upon the exact amount taken. The same tolerance applies to specified dimensions.
          Where the use of a pipette is directed for measuring a specimen or an aliquot in conducting a test or an assay, the pipette conforms to the standards set forth under “Volumetric Apparatus” (Appendix 1.9), and is to be used in such manner that the error does not exceed the limit stated for a pipette of its size. Where a pipette is specified, a suitable burette, conforming to the standards set forth under “Volumetric Apparatus” (Appendix 1.9), may be substituted. Where a “to contain” pipette is specified, a suitable volumetric flask
may be substituted.
          Expressions such as “25.0 mL” and “25.0 mg,” used with respect to volumetric or gravimetric measurements, indicate that the quantity is to be “accurately measured” or “accurately weighed” within the limits stated under “Volumetric Apparatus” (Appendix 1.9) or under “Weights and Balances” (Appendix 1.10).
          The term “transfer” is used generally to specify a quantitative manipulation.
          The term “concomitantly,” used in such expressions as “concomitantly determine” or “concomitantly measured,” in directions for assays and tests, is intended to denote that the determinations or measurements are to be performed in immediate succession.
          Blank Determination Where it is directed that “any necessary correction” be made by a blank determination, the determination is to be conducted using the same quantities of the same reagents treated in the same manner as the solution or mixture containing the portion of the substance under assay or test, but with the substance itself omitted.
          Desiccator The expression “in a desiccator” specifies the use of a tightly closed container of suitable size and design that maintains an atmosphere of low moisture content by means of self-indicating silica gel or other suitable desiccant.
          Drying to Constant Weight The specification “dried to constant weight” means that the drying shall be continued until two consecutive weighings do not differ by more than 0.5 mg per g of substance taken, (2.5 mg per g in case of crude drug), the second weighing following an additional hour of drying at the prescribed conditions.
          Ethanol The term “ethanol” used without other indication means ethanol 95 per cent v/v. Where other strengths are intended, the term “ethanol” is used followed by the statement of the strength.
          Filtration Where it is directed to “filter”, without further qualification, the intent is that the liquid be filtered through suitable filter paper or equivalent device until the filtrate is clear.
          Ignition to Constant Weight The specification “ignite to constant weight” means that the ignition shall be continued until two consecutive weighings do not differ by more than 0.5 mg per g of substance taken, the second weighing following an additional 15-minute ignition period.
          Indicators Unless otherwise directed, where starch is specified in a test or an assay as an indicator, 3 mL of starch TS shall be used; in cases of the other test solutions, approximately 0.2 mL, or 4 drops, of the specified solution shall be added.
          Logarithms Logarithms used in this Pharmacopoeia are to the base 10 and are denoted by the abbreviation “log”. Natural logarithms, if used, are denoted by the abbreviation “ln”.
          Negligible This term indicates a quantity not exceeding 0.5 mg.
          Odour A suitable quantity is left open to the air in an evaporating dish for 15 minutes, after which any odour is defined. An odour designation is descriptive only and is not to be regarded as a standard of purity for a particular lot of an article, except in those cases where a particular odour is specifically prohibited in the individual monograph.
          Percentage Expressions Percentage concentrations are expressed as follows:
          Per cent weight in weight (w/w) expresses the number of g of a constituent in 100 g of solution or mixture.
          Per cent weight in volume (w/v) expresses the number of g of a constituent in 100 mL of solution, and is used regardless of whether water or another liquid is the solvent. Per cent volume in volume (v/v) expresses the number of mL of a constituent in 100 mL of solution. The term “per cent” used without qualification means, for mixtures of solids and semisolids, per cent weight in weight; for solutions or suspensions of solids in liquids, per cent weight in volume; for solutions of liquids in liquids, per cent volume in volume; and for solutions of gases in liquids, per cent weight in volume. For example, a 1 per cent solution is prepared by dissolving 1 g of a solid or semisolid, or 1 mL of a liquid, in sufficient solvent to make 100 mL of the solution. In the dispensing of prescription medications, slight changes in volume owing to variations in room temperatures may be disregarded.
          Pressure Pressure is expressed in kPa.
          - 1 kPa is 7.5006 Torr.
          - 1 Torr is the pressure exerted by a column 1 mm of mercury.
          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, including the indicators and solutions required for the Assay and Tests of the Pharmacopoeia, are defined in the Appendices.
          Reference Standards Reference Standards are authentic specimens that have been verified for suitability for use as comparison standards in Pharmacopoeial tests and assays. (See “Reference Substances”, Appendix 1.8).
          Where a Reference Substance is referred to in an assay or a test in this pharmacopoeia, the words “Reference Substance” are abbreviated to “RS”.
          Where a test or an assay calls for the use of a Pharmacopoeial article rather than a Reference Substance, as a material standard of reference, a substance meeting all of the requirements of the monograph for that article is to be used.
          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. The stability of the contents of opened containers cannot be guaranteed.
          Solutions Unless otherwise specified in the individual monograph, all solutions called for in tests and assays are prepared with water.
          An expression such as “(1 in 10)” means that 1 part by volume of a liquid is to be diluted with, or 1 part by weight of a solid is to be dissolved in, sufficient amount of the diluent or solvent to make the volume of the finished solution 10 parts by volume.
          An expression such as “(20:5:2)” means that the respective numbers of parts, by volume, of the designated liquids are to be mixed, unless otherwise indicated.
          Steam-Bath Where the use of a steam-bath is directed, exposure to actively flowing steam or to another form of regulated heat, corresponding in temperature to that of flowing steam, may be used.
          Temperatures Unless otherwise specified, all temperatures in this Pharmacopoeia are expressed in Celsius degrees, and all measurements are made at 25º. Where “room temperature” is stated, a temperature from 20º to 30º is intended. Absolute temperatures are expressed in Kelvin degrees; the absolute temperature is related to a Celsius temperature by the equation ºK = ºC + 273.16.
          Vacuum The term “in vacuum” denotes exposure to a pressure not exceeding 0.7 kPa (about 5 Torr), unless otherwise indicated.
          Water Where the use of water is specified or implied in identifications, tests and assays, for the preparation of reagents, or as a diluent in any of these circumstances, water complying with the requirements of the monograph on Purified Water is used. The term “distilled water” indicates purified water prepared by distillation.
          Water-Bath Where the use of a water-bath is directed without qualification with respect to temperature, a bath of vigorously boiling water is intended.
          Weights and Measures The metric system of weights and measures is employed in the Pharmacopoeia; the International System of Units (SI) has been adopted wherever practicable. Unless otherwise stated, all measurements involved in the analytical operations of the Pharmacopoeia are intended to be made at 25º.

Crude Drugs

          Crude drugs in the monographs include medicinal parts obtained from plants or animals, their cell inclusions, secretions, and extracts, or minerals