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2015USP 38THE UNITED STATES PHARMACOPEIA1NF 33THE NATIONAL FORMULARYVolum e 4/aBy authority of the United States Pharmacopeial ConventionPrepared by the Council of Experts and its Expert CommitteesOfficial from M ay 1, 2015T h e d e sig n a tio n on the co ve r o f this p u b lic a tio n , "U S P N F 2 0 1 5 ," is fo r ease ofid e n tific a tio n o nly. The p u b lic a tio n co n ta in s tw o separate c o m p e n d ia : The UnitedStates Pharm acopeia, T h irty -E ig h th Revision, and The N a tio n a l Formulary, Thirty-T hirdE dition.THE UNITED STATES PHARMACOPEIAL CO NVENTIO N12601 Twinbrook Parkway, Rockville, M D 20852

SIX-M O N TH IM PLEM ENTATION GUIDELINEThe United States Pharmacopeia-National Formulary and its supplements become official six m onths after being released tothe public. The USP-NF, w hicn is released on November 1 of each year, becomes official on May 1 of the following year. Thissix-month implementation tim ing gives users more time to bring their methods and procedures into compliance with newand revised USP-NF requirements.The table below describes the official dates of the USP-NF and its supplements. The 2014 USP 37-N F 32, and its supple ments, Interim Revision Announcements (IRAs) and Revision Bulletins to that edition, will be official until May 1, 2015, at whichtime the USP 38-N F 33 becomes official.PublicationRelease D a teO ffic ia l D a teO ffic ia l U n tilUSP 38-N F 33November 1, 2014May 1, 2015May 1, 2016 (except as superseded by supplements, IRAs, andFirst Supplement to theUSP 38-N F 33February 1, 2015August 1, 2015May 1, 2016 (except as superseded by Second Supplement, IRAs,and Revision Bulletins)Second Supplement to theUSP 38-N F 33June 1, 2015December 1, 2015May 1, 2016 (except as superseded by IRAs and Revision Bulletins)USP 39-N F 34November 1, 2015May 1, 2016May 1, 2017 (except as superseded by supplements, IRAs, andRevision Bulletins)Revision Bulletins)The table below gives the details of the IRAs that will apply to USP 38-N F 33.IRA O ffic ia l D a teIRAPF P o s tin g D a teCom m ent D u e D a teIRA P o s tin g D a te41(1)lanuarv 2. 2015March 31. 2015Mav 30. 2015lulv 1. 201541(2)March 3, 2015Mav 31. 2015lulv 31. 2015September 1. 201541(3)Mav 1,2015lulv 31. 2015September 26. 2015November 1. 201541(4)lulv 1. 2015September 30. 2015November 26. 2015lanuarv 1, 2016September 2. 2015November 30. 2015lanuarv 30. 2016March 1. 2016November 3, 2015lanuarv 31. 2016March 27. 2016Mav 1, 201641(5)41(6).Revision Bulletins published on the USP website become official on the date specified in the Revision Bulletin.NOTICE A N D W ARNINGConcerning U.S. Patent or Trademark Rights— The inclusion in The United States Pharmacopeia or in the National Formulary of amonograph on any drug in respect to which patent or trademark rights may exist shall not be deemed, and is not intendedas, a grant of, or authority to exercise, any right or privilege protected by such patent or trademark. All such rights andprivileges are vested in the patent or trademark owner, and no other person may exercise the same without expresspermission, authority, or license secured from such patent or trademark owner.Concerning Use of USP or NF Text— Attention is called to the fact that USP and NF text is fully copyrighted. Authors andothers wishing to use portions of the text should request permission to do so from the Secretary of the USPC Board ofTrustees.Copyright 2014 The United States Pharmacopeial Convention12601 Twinbrook Parkway, Rockville, M D 20852All rights reserved.ISSN: 0195-7996ISBN: 978-1-936424-32-0Printed in the United States by United Book Press, Inc., Baltimore, M D

Contents iiiUSP 38-NF 33ContentsVOLUME 1A rticles Included in USP 3 7 But N o tIncluded in USP 3 8 . xliA n n o ta te d List . xliiMission Statement and P re fa c e . viiN o tic e sPeople 2010-2015 Revision Cycle . . . .xvG eneral N o tices and R e q u ire m e n ts .1O f f ic e r s . xvBoard o f T r u s t e e s . xvC o u n c il o f E x p e rts. . xvE xpert C o m m itte e s . . . . xviA d v iso ry G r o u p s . xxivIn M e m o r ia m .G e n e ra l C h a p te rsSee pag e 4 9 for detailed contentsG eneral Tests an d A s s a y s .53G eneral Requirem ents fo r Tests and Assays . . . .53A p p a ra tu s fo r Tests and A s s a y s .96x x ivMembers of the United StatesPharmacopeial Convention,as o f May 31, 2 0 1 4 . .xxvM ic ro b io lo g ic a l T e s ts .10 0B io lo g ica l Tests and A s s a y s .1332 0 1 3 R e c o g n itio n o f M o n o g r a p ha n d R e fe re n ce M a t e r ia l D o n o rs . . . xxxiiC h e m ica l Tests and Assays.216Physical Tests and D e te rm in a tio n s .388G eneral I n f o r m a t io n .69 9A r t ic le s o f I n c o r p o r a t io n . xxxivU SP G o v e r n a n c e . xxxvD ieta ry S u p p le m e n ts .1 751Bylaw s . * x x x vRules and P r o c e d u r e s . x x x vUSP Policies.x x x vA d m is s io n s .xxxixArticles A d m itte d to USP 38 byS u p p le m e n t .x x x ixN e w A rticles A p p e a rin g in USP 38 T h a t W ere N o tIncluded in USP 3 7 In clu d in gS u p p le m e n ts .xlR e a g e n ts, In d ic a to rs , a n dS o lu t io n s1809Reagent S p e c ific a tio n s .18 14Indicators and Indicator Test P a p e r s .1881S o lu tio n s .1884Buffer S o lu t io n s .18 8 4C o lo rim e tric S o lu t io n s .18 85Test S o lu t io n s .1886V o lu m e tric S o lu t io n s .18 9 4C h ro m a to g ra p h ic C o lu m n s .19 0 2

USP 38-NF 33iv ContentsReference TablesC o n ta in e rs fo r D isp e n sin g C apsules andT a b le ts .1 9 0 7D e scrip tio n and Relative S o lu b ility of USPand N F A r t i c le s . .19 17Guide to General C h a p t e r s . viiA p p ro x im a te S o lu bilities of USP andN F A r t ic le s .1 9 76NoticesG eneral N o tic e s a nd R e q u ir e m e n t s .xiA to m ic W eig hts. 1 9 84A to m ic M a s s e s . 1 9 87A lc o h o lo m e tric T a b le . . 1 9 89USP 38Intrinsic V iscosity T a b le . 1991T h e rm o m e tric E q u iv a le n ts . 19 93M onographsIndexO fficia l M o n o g ra p h s fo r USP 38, J - Z .C o m b in e d Index to USP 38 and N F 3 3 .39 991-1IndexVOLUME 2C o m b in e d Index to USP 38 an d N F 3 3 .Cuide to General C h a p t e r s . viiNotices1-1VOLUME 4Guide to General C h a p t e r s . viiG eneral N o tice s and R e q u ire m e n t s .xiNoticesG eneral N o tic e s a nd R e q u ire m e n t s .xiUSP 38Dietary SupplementsM onographsO fficial M o n o g ra p h s fo r USP 38, A - l .19 95IndexC o m b in e d Index to USP 38 and N F 3 3 .1-1O fficia l M o n o g r a p h s .5865

Contents vUSP 38-NF 33.6492USP and N F Excipients, Listed byC a t e g o r y .6493A n n o ta te d ListNF 33ExcipientsA d m is s io n sA rticles A d m itte d to N F 33 b y S u p p le m e n t . . 6491N e w A rticles A p p e a rin g in N F 33 T h a t W ere N o tIncluded in N F 32 In clu d in gS u p p le m e n ts . 6491N e w A rticles A p p e a rin g in N F 33.6491M o n o g ra p h sO fficia l M o n o g ra p h s fo r N F 33 .6503C o m b in e d Index to USP 38 and N F 3 3 .1-1

Guide to General Chapters viiUSP 38Guide to General ChaptersGENERAL TESTS AN D ASSAYSGeneral Requirements(151) Pyrogen T e st. . 211(161) Transfusion and Infusion Assemblies and SimilarMedical D e v ic e s .2 1 2(1 71) Vitamin Bi 2 Activity A ssay.213for Tests and Assays(1) Injections .53(2) Oral Drug Products— Product Quality T e s t s . 66(3) Topical and Transdermal Drug Products—Product Quality Tests . 71(4) Mucosal Drug Products— Product Quality Tests. . . 76(5) Inhalation and Nasal Drug Products—General Information and Product Quality Tests . . 80(7) Labeling . 87(11) USP Reference Standards. 93Apparatus for Tests and Assays(17)(21)(31)(41)Prescription Container L a b e lin g .96Thermometers .98Volumetric Apparatus.99Balances.9 9Microbiological Tests(51) Antimicrobial Effectiveness T e s tin g . 100(55) Biological Indicators— Resistance PerformanceT e s t s . 103(61) Microbiological Examination of NonsterileProducts: Microbial Enumeration T e s t s . 106(62) Microbiological Examination of NonsterileProducts: Tests for Specified Microorganisms . . . 112(63) Mycoplasma T ests. 120(71) Sterility Tests.125Biological Tests and Assays(81)(85)(87)(8 8 )(89)Antibiotics— Microbial A ss a y s . 133Bacterial Endotoxins T e s t .151Biological Reactivity Tests, In Vitro . 156Biological Reactivity Tests, In V iv o . 158Enzymes Used as Ancillary Materials inPharmaceutical Manufacturing . 164(90) Fetal Bovine Serum— Quality Attributes andFunctionality Tests. 167(91) Calcium Pantothenate Assay. 171(92) Growth Factors and Cytokines Used in CellTherapy M anu facturin g. 172(111) Design and Analysis of Biological A s s a y s . 176(115) Dexpanthenol A s s a y . 191(121) Insulin A s s a y s . 193(121.1) Physico-cnemical Analytical Proceduresfor Insu lins. 195(123) Glucagon Bioidentity T e sts. 198(124) Erythropoietin Bioassays.200(126) Somatropin Bioidentity Tests .202(130) Protein A Quality A ttrib u te s . 204Chemical Tests and AssaysIdentification Tests(181)(191)(193)(197)(201)Identification— Organic Nitrogenous Bases . . . 216Identification Tests— General. 216Identification— Tetracyclines. 219Spectrophotometric Identification T ests. 220Tnin-Layer Chromatographic IdentificationT e s t . 221Limit Tests(206) A lu m in u m . 222(207) Test for 1,6-Anhydro Derivative for EnoxaparinSodium . .223(208) Anti-Factor Xa and Anti-Factor Ila Assays forUnfractionated and Low Molecular WeightHeparins. 228(209) Low Molecular Weight Heparin MolecularWeight D e te rm in a tio n s.232(211) A rse n ic .233(221) Chloride and S u lfa te . 235(223) D im ethylaniline. 236(226) 4-Epianhydrotetracycline. 236(227) 4-Aminophenol in Acetaminophen-ContainingDrug Products. 237(228) Ethylene Oxide and D io x a n e .238(231) Heavy M e t a ls . 241(232) Elemental Impurities— Lim its. 243(233) Elemental Impurities— Procedures. 245(241) I r o n .249(251) Lead. 250(261) M e rc u ry . 251(267) Porosimetry by Mercury Intrusion. 253(268) Porosity By Nitrogen Adsorption-Desorption . . 256(271) Readily Carbonizable Substances T e s t . 260(281) Residue on I g n itio n . 260(291) Selenium . 261OtherO th e r TTestse sts aandnd AAssaysss a y ing C a p a city . 261Alginates A s s a y . 262Antimicrobial Agents— C o n ten t.264Assay for Citric Acid/Citrate and Phosphate . . . 267Assay for S te r o id s .268Barbiturate A ssay. 268Cobalamin Radiotracer A s s a y .268General Chapters(For complete alphabetical list of all general chapters in this Pharmacopeia, see under "General chapters" in the index.)