The United States
`Pharmacopeia
`
`TWENTIETH REVISION
`
`Officialfrom July 1, 1980
`
`The National
`
`Formulary _
`
`FIFTEENTH EDITION
`
`Officialfrom July I, 1980
`
`12601 Twinbrook Parkway, Rockville, Md. 20852
`
`United States Pharmacopen&
`
`;
`
`Dr. Reddy's - EX1022
`Page 1
`
`

`

`
`
`United States Pharmacopeia XX
`
`National Formulary XV
`
`OFFICIAL COPY
`J 63477
`
`
`
`Official coupon
`
`Do not remove
`
`NOTICE AND WARNING
`
`Concerning U.S. Patent or Trademark Rights
`The inclusion in the Pharmacopeiaor in the National Formulary of a monograph onany drug
`in respect to which patent or trademark rights may exist shall not be deemed, and is not
`intended as, a grant of, or authority to exercise, any right or privilege protected by such patent
`or trademark. All such rights andprivileges are vestedin the patent or trademark owner, and
`no other person may exercise the same without express permission, authority, or license
`secured fromsuchpatent or trademark owner.
`
`Concerning Use of USP or NFText
`Attention is called to the fact that USP and NF text is fully copyrighted. Authors and others
`wishing to use portions ofthe text should request permissionto do so fromthe Secretary ofthe
`USPC Board of Trustees.
`
`Concerning Laws of Other Countries
`In establishing the Pharmacopeial and National Formulary standards, the USP Committee of
`Revision does not attempt to take into account the laws of countries other than the United
`States of Americadesiring to enforce these standards withintheir jurisdictions.
`
`© 1979 The United States Pharmacopeia] Convention, Inc.
`12601 Twinbrook Parkway, Rockville, Md.
`20852
`
`All rights reserved
`ISSN 0195-7996
`ISBN 0-912734-30-2 (cloth)
`0-912734-31-0 eather)
`
`lyneset and printed by Mack Printing Company, Easton, Pa.
`
`18042
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`Distributed by Mack Publishing Company, Easton, Pa.
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`18042
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`Page 2
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`

`

`USP XX
`
`The United States
`Pharmacopeia
`
`TWENTIETH REVISION
`
`By authority of the United States Pharmacopeial Convention,Inc.,
`meeting at Washington, D. C., March 22, 1975. Preparedby
`the Committee of Revision and published by the Board ofTrustees
`
`Officialfrom July 1, 1980
`
`United States Pharmacopeial Convention, Inc.
`12601 Twinbrook Parkway, Rockvilie, Md. 20852
`
`
`
`USP
`
`Page 3
`
`

`

`Contents
`
`USP XxX
`
`
`
`
`
`People
`
`Officers of the Convention...
`Board of Trustees ..........
`Resources Development
`Advisory Council ......
`USPC Headquarters Staff ...
`General Committee of
`Revision ...........--
`Executive Committee of
`Revision and
`Subcommittees ........
`Reference Standards
`Committee ...........
`Advisory Panels .......-.
`Special Consultants ......-.
`Assistants during 1975-1980
`Membersofthe United States
`Pharmacopeial
`Convention ...........
`
`vill
`vill
`
`vill
`xii
`
`ix
`
`X
`
`X
`Xi
`xii
`xii
`
`Xill
`
`rr
`
`Preamble
`
`General
`
`see page 859for detailed contents
`General Tests and Assays ....
`General Requirements for
`Tests and Assays .......
`Apparatus for Tests and
`ASSAYS oe. ce eee eee
`Microbiological Tests .....
`Biological Tests and Assays
`Chemical Tests and Assays
`Physical Tests and
`936
`Determinations ........
`General Information ........
`992
`
`
`861
`
`861
`
`870
`873
`882
`905
`
`Reagents
`
`1041
`Reagents .........-.0220-
`Indicators and Indicator Test
`1098
`Papers
`.......--20-0005
`1100
`Solutions ..........00000 05
`1100
`Buffer Solutions .........
`1101
`Colorimetric Solutions
`....
`1102
`Test Solutions ..........-
`xix
`Articles of Incorporation ....
`1109
`Volumetric Solutions
`.....
`XX
`Constitution and Bylaws
`....
`Abstract of Proceedings of the
`
`NeeneeeeeneneeneeSEUUUEEEEUESEIESSEIEISISIESSSSNES
`U.S. Pharmacopeial
`Convention, 1975 ......
`History of the Pharmacopeia
`of the United States ....
`Preface to USP XX ........
`
`XXVili
`
` XXxi
`XXXIV
`
`Tables
`
`...
`
`1117
`
`Containers for Dispensing
`Capsules and Tablets
`Description and Relative
`Solubility of USP and
`NF Articles ..........-
`Approximate Solubilities of
`USP and NF Articles ...
`1160
`Admissions—Articles Admitted to USP
`USP and NF Pharmaceutic
`XIX and NF XIV by
`Ingredients, Listed by
`Supplement
`......----
`Categories ........-065 1168
`New Admissions to the
`Atomic Weights .........--
`1171
`Official Compendia ....
`Molecular Formulas and
`Changesin Official Titles...
`Weights ........---+65 1172
`Articles Included in USP XIX
`Alcoholometric Table .......
`1187
`but Not Included in USP
`Thermometric Equivalents ...
`1188
`XX orin NF XV ......
`Equivalents of Weights and
`Articles Included in NF XIV
`Measures ........-.-05 1189
`but Not Included in NF
`Table of Metric-Apothecary
`hii
`XV orin USP XX .....
`Approximate Dose
`
`Equivalents
`.. .inside back cover
`$=
`
`ne
`
`112i
`
`xiii
`
`xhili
`l
`
`lit
`
`General Notices and
`Appendix
`Requirements ........-
`1273
`Antibiotic Regulations ......
`neeeEEEEEEEIEEEEESEEEES
`
`Notices
`
`Combined Index to USP XX
`Official Monographs of USP
`onographs
`and NF XV
`XX ooo c ce ceveueeecees
`
`neEEUTEEEEEEINESSIRS
`ne
`
`Index
`
`1 M
`
`vil
`
`

`

`USF AA
`
`regardless of whether the values are expressed as per-
`centages or as absolute numbers, are consideredsig-
`nificant to the last digit shown.
`Equivalence Statements in Titrimetric Proce-
`dures—-Thedirectionsfor titrimetric procedures con-
`clude with a statementof the weight of the analyte that
`is equivalent to each mlofthe standardized titrant.
`In
`such an equivalence statement, it is to be understood
`that the numberofsignificant figures in the concen-
`tration ofthe titrant corresponds to the number ofsig-
`nificant figures in the weight of the analyte. Blank
`corrections are to be made forall titrimetric assays,
`where appropriate (see Titrimetry (S41)).
`The limits specified in the monographs for Phar-
`macopeialarticles are established with a view to the use
`of these articles as drugs, except where the monograph
`indicates that the article is intended foruse in in-vitro
`diagnostic procedures or as a medical device. The use
`of the molecular formula for the active ingredient(s)
`named in defining the required strength of a Pharma-
`copeial article is intended to designate the chemical
`entity or entities having absolute (100 percent) pu-
`rity,
`The quantity of each ingredient used in preparing the
`dosage forms shall be equivalent to not less than 100
`percent of the quantity called for in the formula orof
`the amount declared on thelabel.
`The tolerances and limits stated in the definitionsin
`the monographs for Pharmacopeialarticles allow for
`analytical error, for unavoidable variations in manu-
`facturing and compounding, and for deterioration to
`an extent considered insignificant under practical
`conditions. Notwithstanding these tolerances,
`the
`objective of the Pharmacopeiai standardsfor a dosage
`form or a finished device is to achieve a product whose
`strength is 100 percentof the quantity of the absolutely
`pure chemical entity or entities named on the label as
`the active ingredient(s).
`The specified tolerances are based upon such at-
`tributes of quality as might be expected to characterize
`an article produced from suitable raw materials under
`recognized principles of good manufacturing prac-
`tice.
`The existence of compendial limits or tolerances does
`not constitute a basis for a claim that an official sub-
`stance that more nearly approaches 100 percent purity
`“exceeds” the Pharmacopeial quality. Similarly, the
`fact that an article has been preparedto closertoler-
`ances than those specified in the monograph does not
`constitute a basis for a claim that the article “exceeds”
`the Pharmacopeial requirements.
`
`ALCOHOL
`
`All statements of percentages of alcohol, such as
`under the heading, Alcohol content, refer to percentage,
`by volume, of CpHsOHat 15.56°. Where reference
`is made to “C>H5OH,” the chemical entity possessing
`absolute (100 percent) strength is intended.
`Alcohol—Where “alcohol”is called for in formulas,
`tests, and assays, the monographarticle Alcoholts to
`be used.
`Dehydrated Alcohol—Where “dehydrated alcohol”
`(absolute alcohol) is called fer in tests and assays, the
`
`UETLETUL LVULICES
`
`J
`
`reagent Dehydrated Alcohol (see in the section, Re-
`agents, Indicators, and Solutions) is to be used.
`Denatured Alcohol—In the manufacture of Phar-
`macopeial preparations in which alcohol is used only
`as a solvent and does not remain in the finished product,
`alcoho!specially denatured bythe addition of volatile
`substances,
`in accordance with federal statutes and
`regulations of the Internal Revenue Service, may be
`substituted but
`the preparations so made must be
`identical with those prepared by the processesgiven in
`the monographs and must conform to the Pharmaco-
`peial standardsset forth.
`
`REAGENT STANDARDS
`
`The proper conduct of the Pharmacopeial tests and
`assays and thereliability of the results depend,in part,
`uponthe quality of the reagents used in the performance
`of the procedures. Unless otherwise specified, reagents
`are to be used that conformto the standardsset forth
`in the current edition of Reagent Chemicals published
`by the American ChemicalSociety. Where such ACS
`reagentstandardsare not available or where for various
`reasons the required purity differs, compendial speci-
`fications for reagents of acceptable quality are provided.
`(See Reagents, Indicators, and Solutions.) Listing
`of these reagents, including the indicators and solutions
`employedas reagents, in no way implies that they have
`therapeuticutility; furthermore, any reference to USP
`in their labeling shall include also the term “reagent”
`or “reagent grade.”
`
`REFERENCE STANDARDS
`
`USP Reference Standards and U. S. Reference
`Standardsfor antibiotics are authentic specimens that
`have beenverified for suitability for use as comparison
`standards in compendia] tests and assays.
`(See USP
`Reference Standards (11).)
`Wherefirst referred to in a monograph, the name of
`a USP Reference Standardis generally spelled out in
`full. However, where a USP Reference Standardis
`referred to thereafter in an assay or a test in this com-
`pendium, the words “Reference Standard”are abbre-
`viated to “RS.”
`Wherea test or an assay calls for the use of a com-
`pendial article, rather than a USP Reference Standard,
`as a material standard of reference, a substance mecting
`all of the requirements of the monograph for thatarticle
`is to be used.
`
`UNITS OF POTENCY
`
`For those products for whichit is necessaryto express
`the potency in termsofunits by reference to a suitable
`working standard (usually a USP Reference Standard),
`the individual monographsrefer to USP Units of ac-
`tivity. Unless otherwise indicated, USP Units are
`equivalent to the corresponding international units,
`where such exist, and to the units of activity established
`by the Food and Drug Administration in the case of
`antibiotics and biological products.
`
`INGREDIENTS AND PROCESSES
`
`Pharmacopeial dosage forms and finished devices are
`prepared from ingredients that meet the requirements
`
`Page 5
`
`

`

`4
`
`General Notices
`
`of the compendial monographs for those individual
`ingredients for which monographsare provided. Water
`used as an ingredientin the preparation of compendial
`dosage forms meets the requirements for Purified
`Water, or for Water for Injection, or for one of the
`sterile forms of water covered by a monographin this
`Pharmacopeia.
`Potable water maybe used in the preparation of of-
`ficial substances.
`It meets the requirements for
`drinking water as set forth in the regulations of the
`federal Environmental! Protection Agency.
`Preparations for which a complete composition is
`given in this Pharmacopeia, unless specifically ex-
`empted herein or in the individual monograph, are to
`contain only the ingredients named in the formulas.
`However, there maybe deviation from the specified
`processes or methods of compounding, though not from
`the ingredients or proportions thereof, provided the
`finished preparation conformsto the relevant standards
`laid down herein and to preparations producedbyfol-
`lowing the specified process.
`Where a monograph on a preparationcalls for an
`ingredient in an amount expressed on the dried basis,
`the ingredient need not be dried prior to use if due al-
`lowance is made for the water or other volatile sub-
`stances present in the quantity taken.
`Unless specifically exempted elsewhere in this
`Pharmacopeia, the identity, strength, quality, and pu-
`rity of anofficial article are determined by the defini-
`tion, physical properties, tests, assays, and other spec-
`ifications relating to the article, whether incorporated
`in the monographitself, in the General Notices, or in
`the section, General Chapters.
`Uniformity of Composition— While a demonstration
`of homogeneity in individual units of a given lot of a
`Pharmacopeial dosage formorfinished devicesmay not
`always be practicable, variations in composition are
`undesirable and substantial differences in the content
`of active ingredient(s) among individual capsules,
`tablets, and other finished forms are to be avoided.
`Where, because of the small amount of active sub-
`stance(s) in the individual finished forms, the Weight
`variation test (see (931)) cannot give the necessary
`assurancethat successive units from the same container
`will contain substantially uniform amounts,a test for
`Content uniformity (see (681)) is provided wherever
`practicable.
`(See also Preface.)
`Added Substances—An official substance, as dis-
`tinguished from a dosage form, contains no added
`substances except where specifically permitted in the
`individual monograph. Where such addition is per-
`mitted, the label indicates the name(s) and amount(s)
`of any added substance(s).
`Unless otherwise specified in the individual mono-
`graph, or elsewhere in the General Notices, suitable
`substances such as bases, carriers, coatings, colors,
`flavors, preservatives, stabilizers, and vehicles maybe
`rt
`ro on
`att
`.
`«
`iit
`.
`d
`1
`added to a Pharmacopeial dosage form orfinished de-
`vice to enhanceits stability, usefulness, or elegance, or
`to facilitate its preparation. Such substances may be
`regarded as suitable only if they are harmless in the
`amounts used, if they do not exceed the minimum
`quantity required to provide their intended effect, if
`their presence does not impair the bioavailability or the
`
`ISP XX
`
`therapeutic efficacy of the dosage form, and if they do
`not interfere with the assays and tests prescribed for
`determining compliance with the Pharmacopeial
`standards.
`Colors—Added substances employed solely to im-
`part color may be incorporated into Pharmacopeial
`articles that are dosage formsor finished devices, except
`those intended for parenteral or ophthalmic use,
`in
`accordance with the regulations pertaining to the use
`of colors in drugs issued by the Food and Drug Ad-
`ministration, provided such added substancesare oth-
`erwise appropriate in all respects.
`(See also Added
`Substances under Injections (1).)
`Capsules and Tablets—Capsules and tablets may
`be made with suitable diluents, colors,
`lubricants,
`disintegrants, and adhesives, such asstarches,lactose,
`sucrose, and other innocuous materials. Tablets and
`the contents of capsules that are intended to be homo-
`geneous are uniformin appearance within a given lot.
`Excessive amountsof substances that may impair bio-
`availability of the active ingredients are to be avoided.
`Tablets maybe coated.
`the
`Parenteral and Topical Preparations—F¥or
`preservation of preparations intended for parenteral
`administration or topical application, suitable antiox-
`idants, antimicrobial agents, buffers, and/or stabilizers
`maybe added unless interdicted in the monograph.
`For requirements concerning the presence and pro-
`portions of added substancesin parenteral preparations,
`and the pertinent labeling requirements, see Added
`Substances and Labeling under Injections (1).
`Theair in a containerofan article for parenteral use
`maybe evacuated or be replaced by carbon dioxide,
`helium, or nitrogen, or by a mixture of these gases,
`which fact need not be declared on the label unless
`otherwise specified in the individual monograph.
`Ointments and Suppositories——\n the preparation
`of ointments and suppositories, the proportions of the
`substances constituting the base may be varied to
`maintain a suitable consistency underdifferent climatic
`conditions, provided the concentrations of active in-
`gredients are not varied.
`
`TESTS AND ASSAYS
`
`Apparatus—A specification for a definite size or type
`of container or apparatusin a test or assayis given solely
`as a recommendation. Where volumetric flasks 6r
`other exact measuring, weighing, or sorting devices are
`specified, this or other equipmentofat least equivalent
`accuracy shall be employed.
`(See also Volumetric
`Apparatus (31).)
`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
`ncedA.
`In order to obtain solutions having concentra-
`tions that are adaptable to the working range of the
`instrument being used, solutions of proportionately
`higher or lower concentrations may be prepared, ac-
`cording to the solvents and proportions thereof that are
`specified for the procedure.
`Where a particular brand or source of a material or
`piece of equipment, or the name and address of a
`
`Page 6
`
`

`

`
`
`12
`
`Acetaminophen / Official Monographs
`
`for 30 minutes, and centrifuge at 1000 rpm for 15 minutes or until
`a clean separation is obtained. On a suitable thin-layer chroma-
`tographicplate (see (621)), coated with a 0.25-mm layer of chro-
`matographicsilica gel mixture, apply 200 yl of the supernatant
`liquid, in 40-11 portions, to obtain a single spot not more than 10 mm
`indiameter. Similarly apply40 pl of a Standard solution in ether
`containing 10 yg of p-chloroacetanilide per ml, and allow the spots
`to dry. Develop the chromatogram,in an unsaturated chamber,
`with a solvent system. consisting of solvent hexane and acetone
`(75:25), until the solvent front has moved three-fourths of the length
`of the plate. Remove the plate from the developing chamber, mark
`the solvent front, and allow the solvent to evaporate. Locate the
`spots in the chromatogram by examination under short-wavelength
`ultraviolet light:
`any spot obtained from the solution undertest,
`at an Ry value correspondingto the main spot from the Standard
`solution, is not greater in size or intensity than the main spot ob-
`tained from the Standardsolution, corresponding to not more than
`0.001% of p-chloroacetanilide.
`Assay—Dissolve about 120 mg of Acetaminophen, accurately
`weighed, in 10 ml of methanol in a S00-ml volumetric flask, dilute
`with water to volume, and mix. Transfer 5.0 mlofthis solution to
`a 100-ml! volumetric flask, dilute with water to volume, and mix.
`Concomitantly determine the absorbancesofthis solution and of
`a Standard solution of USP Acetaminophen RS, in the same me-
`dium, at a concentration of about 12 yg per mlin 1-cmcells, at the
`wavelength of maximum absorbanceat about 244 nm, with a suit-
`able spectrophotometer,using water as the blank. Calculate the
`quantity, in mg, of CgH9NOyin the Acetaminophen taken bythe
`formula 10C(Ay/As), in which C is the concentration, in wg per
`ml, of USP AcetaminophenRSin the Standard solution, and Ay
`and Ag are the absorbancesof the solution of Acetaminophen and
`the Standard solution, respectively.
`
`Acetaminophen Capsules
`
`» Acetaminophen Capsulescontain not less than 95.0
`percent and not more than 105.0 percentof the labeled
`amount of CgHgNQOdo.
`Packaging and storage—Preservein tight containers.
`Reference standard—USP Acetaminophen Reference Stan-
`dard —Dry oversilica gel for 18 hours before using.
`Identification—
`A:
`Theultraviolet absorption spectrum ofthe solution of the
`Capsules prepared for the measurementof absorbance in the Assay
`exhibits maxima and minimaat the same wavelengthsas thatof a
`similar solution of USP Acetaminophen RS,concomitantly mea-
`sured.
`B: Triturate an amount of the contents of the Capsules,
`equivalent to about | g of acetaminophen, with 30 ml of warm al-
`cohol, cool, and filter. To 3 mlofthe filtrate add 10 ml of water
`and | drop of ferric chloride TS, and mix:
`a violet-blue coloris
`produced.
`Weightvariation (931): meet the requirements for Capsules.
`Assay —
`Standard preparation and Chromatographic column—Prepare
`as directed in the Assay under Acetaminophen Elixir.
`Assay preparation—Weigh the contents of not fewer than 20
`Acetaminophen Capsules. Mix the contents, and transfer an ac-
`curately weighed portion of the powder, equivalent to about 250 mg
`of acetaminophen,to a 250-m! volumetric flask, add 2 ml of | N
`sodium hydroxide, dilute with water to volume, mix, and filter,
`discarding the first 20 ml of the filtrate. Proceed as directed for
`Assay preparationin the Assay under Acetaminophen Elixir, be-
`ginning with “Transfer 2.0 ml of this solution to a 100-ml
`beaker.”
`Procedure—Proceed as directed for Procedure in the Assay
`under AcetaminophenElixir. Calculate the quantity, in mg, of
`CgHoNO,in the portion of the Capsules taken by the formula
`31.25C(Ay/As), in which C is the concentration, in zg per ml, of
`USP Acetaminophen RSin the Standardpreparation, and Ayand
`Ag are the absorbancesof the Assay preparation and the Standard
`preparation, respectively.
`
`USP XX
`
`Acetaminophen Elixir
`» AcetaminophenElixir contains not less than 95.0
`percent and not more than 105.0 percent of the labeled
`amount of CgHogNOdz.
`Packaging and storage—Preserve in tight containers, and avoid
`continuous exposure to excessive cold.
`Reference standard—USP Acetaminophen Reference Stan-
`dard—Dryoversilica gel for 18 hours before using.
`Identification—The ultraviolet absorption spectrum of a portion
`of the Assay preparation employed for measurement of absorbance
`in the Assay exhibits maxima and minimaat the same wavelengths
`4s that ofa similar solution of USP Acetaminophen RS, concomi-
`tantly measured.
`pH (791): between 3.8 and 6.1.
`Alcohol content (611);
`between 6.5% and 10.5% of C,Hs50H,
`determined by the gas-liquid chromatographic procedure, acetone
`being used as the internal standard.
`Assay—
`Standard preparation—Transfer about 80 mg of USP Acet-
`aminophenRS,accurately weighed, toa 100-ml volumetric flask,
`add methanol to volume, and mix. Transfer 10.0 mi ofthis solution
`to a second 100-mlvolumetric flask, dilute with methanol to volume,
`and mix. Transfer 10.0 ml of the resulting solution to a 100-ml
`volumetric flask, add ] ml of 0.1 N hydrochloric acid, then add
`methanol to volume, and mix.
`Chromatographiccolumn—Packa pledgetoffine glass woolin
`the base of a chromatographic tube (25-mm X 250-mm tube to
`which is fused a S-cm length of 7-mm tubing) with the aid of a
`tamping rod about45 cm in length and having a disk with a diameter
`about 1 mm less than that of the tube. To 2 g ofpurified siliceous
`earth ina 100-ml beaker add 2.0 mlofa solutioncontaining 1.0 g
`of sodium bicarbonate and 4.5 g of sodium carbonatein each 100
`ml, and mix until a fluffy mixture is obtained. Transfer the mixture
`to the chromatographic tube, and tamp gently to compress the
`material to a uniform mass.
`Assay preparation—Transfer an accurately measured volume
`of AcetaminophenElixir, equivalent to about 250 mg of acetami-
`nophen, to a 250-mlvolumetric flask, add 2 ml of 1 N sodium hy-
`droxide, dilute with water to volume, and mix. Transfer 2.0 ml of
`this solution to a 100-ml beaker, add 1 drop of hydrochloric acid,
`swirl to mix, then add 3.0 g ofpurified siliceous earth. Mix, and
`transfer to the chromatographic column. Scrub the beaker with
`1 g ofpurified siliceous earth mixed with 2 drops of water, transfer
`the washings to the column, and tampgently. Place a pledget of
`fine glass wool on top of the column. Wash the column with 100
`miof water-saturated chloroform, and discard the eluate. Elute
`the acetaminophenwith 150 mlof water-saturated ether, collecting
`the eluate in a 400-ml beaker. Evaporate the ether on a steam bath
`with the aid of a currentof air just to dryness.
`[NOTE—Avoid
`prolonged drying, to prevent loss of acetaminophen.] Without
`delay, dissolve the residue in a solvent mixture consisting of | ml
`of dilute hydrochloric acid (1 in 100) per 100 ml of methanol, and
`transfer to a 50-m! volumetric flask. Rinse the beaker with the
`solvent mixture, adding the rinsings to the flask, dilute with the
`solvent mixture to volume, and mix. Transfer 10.0 ml ofthis so-
`lution to a second 50-ml volumetric flask, dilute with the solvent
`mixture to volume, and mix.
`Procedure-—Concomitantly determine the absorbancesof the
`Standard preparation and the Assay preparation in |-cm cells at
`the wavelength of maximum absorbanceat about 249 nm, with a
`suitable spectrophotometer,using a solvent mixture consisting of
`| ml of 0.1 NV hydrochloric acid per 100 ml of methanolas the blank.
`Calculate the quantity, in mg, of CgHoNO3;in each mlof Elixir
`taken by the formula 31 .25(C/V)(Au/As), in which C is the con-
`centration, in zg per ml, of USP Acetaminophen RS in the Stan-
`dard preparation, V is the volume,in ml, of Elixir taken, and Ay
`and As are the absorbances of the Assay preparation and the
`Standard preparation, respectively.
`
`Acetaminophen Tablets
`» Acetaminophen Tablets contain notless than 95.0
`
`Page 7
`
`Td
`
`dis
`the
`fer
`Re
`anc
`
`Ad
`hycanc
`mir
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`

`

`
`
`16
`
`Acetophenazine / Official Monographs
`
`Procedure—Inject a suitable volume, typically about 5 bl, of
`Acetoneinto a suitable gas chromatograph, and record the chro-
`matogram. Calculate the percentage of C3H¢O in the Acetone,
`on the anhydrousbasis, bydividing the area under the acetone peak
`by the sumof the areas underall of the peaks and multiplying by
`100.
`[NOTE—Noseparate correction is applied for water content,
`since water does not respond to the flame-ionization detector.]
`
`Acetophenazine Maleate
`
`N—CH,CH,0H
`CH,CH,CH»—N
`|
`VS
`
`NUN _UCOCH,Oo
`
`HE—-COOH
`HC—COOH
`
`643.71
`Co3H 29N 3028 : 2CsH4O4
`Ethanone, 1-[10-[3-[4-(2-hydroxyethyl)-1-piperaziny]] propyl]-
`10H-phenothiazin-2-yl]-, (Z) 2-butenedioate (1:2) (salt).
`10-[3-[4-(2-Hydroxyethyl)-l-piperazinyl ]propy!] phenothiazin-
`2-y! methy! ketone maleate (1:2) (salt)
`{5714-00-1].
`» Acetophenazine Maleate, dried at 65° for 4 hours,
`contains not less than 97.0 percent and not more than
`103.0 percent of C33H 29N302S8 2C4H 404.
`Packaging and storage—Preservein tight containers.
`Reference standard—USP Acetophenazine Maleate Reference
`Standard—Dryat 65° for 4 hours before using.
`Identification—
`A: The infrared absorption spectrum of a mineral oil dispersion
`ofit, previously dried, exhibits maxima only at the same wavelengths
`aethat of a similar preparation of USP Acetophenazine Maleate
`RS.
`B: The ultraviolet absorption spectrum ofa |
`in 100,000 solu-
`tion in methanol exhibits maxima and minimaat the same wave-
`lengths as thatof a similar solution of USP Acetophenazine Maleate
`RS, concomitantly measured, and the respective absorptivities,
`calculated on the dried basis, at the wavelength of maximumab-
`sorbance at about 243 nm do not differ by more than 3.0%.
`C:
`Prepare a solution in methanoJcontaining | mgper ml. On
`a suitable thin-layer chromatographicplate (see (621)), coated with
`a 0.25-mmlayer of chromatographicsilica gel mixture, spot 10 ul
`of this solution and 10 ul of a solution of USP Acetophenazine
`Maleate RS in methanolcontaining | mg per ml. Allowthe spots
`to dry, and develop the chromatogramin a solvent system consisting
`of acetone and ammonium hydroxide (95:5) until the solvent front
`has moved about three-fourths of the length of the plate. Remove
`the plate fromthe developing chamber, mark the solventfront, and
`allow the solvent to evaporate. Locatethe spots using long-wave-
`lengthultraviolet light:
`the Ry value of the main spot obtained from
`the test solution corresponds to that obtained from the Standard
`solution.
`Loss on drying (731)—Dryit at 65° for 4 hours:
`than 0.5%of its weight.
`Residue on ignition (281): not more than 0.1%.
`Assay—Dissolve about 500 mg of Acetophenazine Maleate,pre-
`viously dried and accurately weighed,in 50 mlof glacial acetic acid,
`warming slightly to effect solution. Cool to room temperature, add
`10 ml ofacetic anhydride,andaliow to stand for 5 minutes. Add
`| drop ofcrystal violet TS, and titrate with 0.1 perchloric acid
`VS toa green-yellow end-point. Perform a blank determination,
`and make any necessary correction. Each mJ of 0.1 N perchloric
`acidis equivalent to 32.19 mg of Co3H29N 3028. 2C4HyO4.
`
`it loses not more
`
`Acetophenazine Maleate Tablets
`» Acetophenazine Maleate Tablets contain not less
`than 90.0 percent and not more than 110.0 percent of
`the labeled amount of Cy3Ho9N302S.. 2C4H4Ou.
`Packaging and storage—Preservein tight containers.
`Reference standard—USP Acetophenazine Maleate Reference
`Standard—Dry at 65° for 4 hours before using.
`
`USP XX
`
`finely powdered Tablets,
`[dentification——Heat a quantity of
`equivalent to about 20 mg of acetophenazine maleate, with 20 ml
`of methanol ona steam bathfor 5 minutes, with occasional swirling.
`Cool to room temperature, add methanolto restore to original
`volume, shakevigorously for 2 minutes, andfilter. A 10-1 portion
`ofthefiltrate responds to /dentification test C under Acetophena-
`zine Maleate.
`Disintegration (701); 30 minutes.
`Content uniformity (681): meet the requirements for Tablets.
`Assay~—
`Standard preparation—Transfer about 20 mg of USP Aceto-
`phenazine Maleate RS, accurately weighed, to a separator, and
`proceed as directed under Assay preparation, beginning with “add
`50 mlof sodium chloride solution (1 in 5).” The concentration of
`USP Acetophenazine Maleate RSin the Standard preparation is
`about 10 «wg per ml.
`Assay preparation—Weigh andfinely powdernot less than 20
`Acetophenazine Maleate Tablets. Transfer an accurately weighed
`portion of the powder, equivalent to about 20 mg of acetophenazine
`maleate, to a separator, add 50 ml of sodium chloride solution (1
`in 5) and sufficient 2.5 N sodium hydroxide to adjust toa pHof 11,
`and allow to cool to room temperature. Extract with four 40-m]
`portions of solvent hexane. Extract the combined solvent hexane
`solution with three 50-ml portions of 0.1 N hydrochloric acid,
`combining the acid extracts in a 200-ml volumetric flask. Dilute
`with 0.1 N hydrochloric acid to volume, and mix. Transfer 10.0
`ml of this solution to a 100-ml volumetric flask, dilute with 0.1 N
`hydrochloric acid to volume, and mix.
`Procedure—Concomitantly determine the absorbances of the
`Assaypreparation and the Standard preparation in l-cm cells at
`the wavelength of maximum absorbanceat about 278 nm,with a
`suitable spectrophotometer, using 0.1 Nhydrochloric acid as the
`blank, Calculate the quantity, in mg, of C73H29N 3028 .2C4H4O4
`in the portion of the Tablets taken by the formula 2C(Au/As), in
`which Cis the concentration,in zg per ml, of USP Acctophenazine
`Maleate RSin the Standard preparation, and Ay and Agare the
`absorbances of the Assay preparation and the Standard prepara-
`tion, respectively.
`
`Acetylcysteine
`
`NHCOCH,
`HSCHa----C-="-COOH
`H
`
`163.19
`CsHoNO3S
`L-Cysteine, V-acetyl-.
`[616-91-1).
`N-Acetyl-L-cysteine
`» Acetylcysteine containsnotless than 98.0 percent
`and not more than 102.0 percent of Cs5H9NQs38S, cal-
`culated on the dried basis.
`Packaging and storage—Preservein tight containers.
`Reference standard—USP Acetylcysteine Reference Standard—
`Dry at 70° and ata pressure of about 50 mm of mercury for 4 hours
`before using.
`Identification—The infrared absorption spectrum of a mineral oil
`dispersion ofit, previously dried, exhibits maximaonly at the same
`wavelengthsasthatof a similar preparation of USP Acetylcysteine
`RS.
`Melting range, Class / (741): between 104° and 110°.
`Specific rotation (781)—In a 25-ml volumetric flask mix 1.25 g
`with | ml of disodium ethylenediaminetetraacetate solution (1 in
`100), add 7.5 ml of sodium hydroxidesolution (1 in 25), and mix
`to dissolve. Dilute to volume with pH 7.0 buffer (prepared by
`mixing 29.5 ml of 1 N sodium hydroxide, 50 mlof1 M monobasic
`poiassium phosphate, and sufficient water to make 100 ml and,
`using a pH meter, adjusting to a pH of 7.0 + 0.1 by adding, as
`necessary, moreofeither solution):
`the specific rotation, calculated
`on the dried basis, compared with a blank prepared with the same
`amountsof the same reagents, is between +21° and +27°.
`pH (791): between 2.0 and 2.8, in a solution (1 in 100).
`Loss on drying (731)—Dryit at 70° andata pressureof about 50
`mmof mercury for 4 hours:
`it loses not more than 1.0%ofits
`weight.
`
`al
`ct
`ce
`th
`
`of
`lir
`Ags
`
`mi
`co
`cu
`us
`nit
`
`Aci
`
`Aci
`
`CioH
`1,3-B
`4-He
`[
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`
`Packa
`
`Page 8
`
`

`

`USP AX
`
`Physical Tests / Content Uniformity
`
`955
`
`Torque Applicable to Screw-Type Container
`
`Suggested Tightness Range
`with Manually Applied Torque?
`Closure Diameter!
`(inch-pounds)
`(mm)
`6 to9
`15
`7 toll
`18
`8 to 12
`20
`9 to 13
`22
`10 to 15
`24
`11 to 17
`28
`13 to 20
`33
`15 to 23
`38
`17 to 26
`43
`19 to 29
`48
`21 to 32
`53
`23 to 35
`58
`25 to 38
`63
`28 to 42
`70
`34 to 49
`83
`35 to 51]
`86
`36 to 53
`89
`40 to 60
`100
`45 to 65
`110
`48 to 72
`120
`
`132 53 to 79
`
`' The torque designated for the next larger closure diameteris
`to be applied in testing