11 USP REFERENCE STANDARDS

11USPREFERENCESTANDARDS美国药典对照品USPReferenceStandardsarehighlycharacterizedspecimensofdrugsubstances,excipients,reportableimpurities,degradationproducts,compendialreagents,andperformancecalibrators.TheyareexplicitlyrequiredinmanyPharmacopeialassaysandtestsandareprovidedsolelyforsuchuse.Assessmentofthesuitabilityforuseinotherapplication(s)restswiththepurchaser.AUTHORITYFORESTABLISHMENTANDRELEASEUSPReferenceStandardsareestablishedandreleasedundertheauthorityoftheUSPCBoardofTrusteesuponrecommendationoftheUSPReferenceStandardsExpertCommittee,whichapproveseachlotasbeingsuitableforuseinitscompendialapplications.ForsomeReferenceStandardsapreliminaryreviewandapprovalissoughtfromotherExpertCommitteesoftheCouncilofExperts.ThedistributionofcontrolledsubstancesissubjecttotheregulationsandlicensingprovisionsoftheDrugEnforcementAdministrationoftheDepartmentofJustice.IndustryAdvisoryPanelsandotherexpertgroups(suchasProjectTeams)maybeassembledtoadviseUSPonvariousaspectsoftheReferenceStandardsProgram.HISTORYFutureavailabilityofthefirstUSPReferenceStandardswasannouncedin1926(USPX)“…inordertofacilitatetheadoptionofthebiologicalassaystandardsofthePharmacopoeia,andtoprovideagreaterdegreeofuniformityintheirapplication.”ThelistofUSPReferenceStandardsthatin1936comprised6itemshasgrowntoalmost1650in2004,andthecollectionhastrackedtheprogressinpharmaceuticalsciences:Thefirstvitamins(CodLiverOil)andthefirstenzyme(Pepsin)in1936;thefirstsulfonamide(Sulfanilamide)andthefirsthormones(Insulin;PosteriorPituitary)in1942;thefirstperformancestandards(MeltingPointStandards)in1947;thefirstpenicillin(PenicillinGSodium)in1950;thefirstrecombinant-DNAtechnologyprotein(InsulinHuman)in1985,etc.ThecontinuousincreaseinthenumberofUSPReferenceStandards(over100newstandardsarebeingdevelopedyearly)reflectsnotonlytheincreaseinthenumberofmonographsandGeneralChapters,butalsothedevelopmentandextensiveuseofmodernanalyticalmethodology(suchaschromatography,spectrophotometry,biologicalandbiochemicalassays,etc.)whichrequiremeasurementsrelativetoareferencestandard.NOMENCLATUREStandardsdesignatedasUSPReferenceStandards(USPRS)are,withafewexceptions,requiredforuseinUSP–NFmonographsorGeneralChapters.TheexceptionsincludecurrentlotsofUSPandNFReferenceStandardsforwhichusesarenolongerspecifiedinthecurrentUSPorNFbutforwhichsufficientdemandremains(upondepletionofthecurrentlots,futurelotswillbedesignatedasAuthenticSubstances),ReferenceStandardsspecifiedinmonographsdevelopedbyUSPthatarenotintendedforpublicationintheUSP–NF,ReferenceStandardsspecifiedinthecurrenteditionoftheFoodChemicalsCodex(labeledwithanadditionaldesignation“FCC”),andFluorideDentifrices(evaluatedanddistributedbyagreementwiththeFDAandtheCosmetics,Toiletries,andFragrancesAssociation).AUSPReferenceStandardrequiredinamonographorGeneralChapterproposedinPharmacopeialForummaybereleasedinadvanceoftheofficialdateoftheproposedPFrevision.ReferenceStandardscurrentlylabeledas“NFReferenceStandards”willeventuallyallbedesignatedandlabeledas“USPReferenceStandards”pursuanttotheconsolidationofUSPandNFwithintheUSPCasofJanuary2,1975.Meanwhile,whereaUSPReferenceStandardiscalledfor,thecorrespondingsubstancelabeledasan“NFReferenceStandard”maybeused.Asaservice,theUSPCtestsanddistributesadditionalAuthenticSubstances(designatedbyAS)notcurrentlyrequiredforuseinaUSPmonographorGeneralChapter.ThesealsoareprovidedunderthesupervisionoftheUSPReferenceStandardsExpertCommittee.Theyarehighlycharacterizedsamplesofchemicals,includingsubstancesofabuse,whicharecollaborativelytestedandmadeavailableasaserviceprimarilytoanalytical,clinical,pharmaceutical,andresearchlaboratories.Suchmaterialsmaybeusedforidentification,methoddevelopment,evaluationofmethodperformance,orotherapplicationsasfoundsuitableandvalidatedbytheuser.AuthenticVisualReferencesUnlikechemicalreferencestandards,AuthenticVisualReferences(AVRs)arenotusedinchemicalanalyses.Instead,theAVRsarevisualimagesusedbyanalyststocomparecertaintestarticlestoensurethattheymeetcompendialrequirementsandareincorporatedbyreferenceintothemonograph.ApprovalofAVRsforuseinamonographisthedecisionoftheExpertCommitteethatapprovesthespecificmonograph.DIVERSITYANDIMPLICATIONSTheUSPReferenceStandardscollectionisverydiverseintermsofappearance,chemicalstructure,composition,anduses.Thisdiversityhassignificantimplicationsforthewaythematerialsaretested,packaged,stored,andutilized.TheUSPReferenceStandardsmaybecrystallineoramorphouspowders,volatileorviscousliquids,solutionsorsuspensions,gelsorpastes,plasticsheets,etc.InchemicalstructuretheyvaryfromsimpleinorganicsaltstoproteinsproducedbyrecombinantDNAtechnology.Somearehighly-purifiedsinglecomponents,whileothersarecomplexmixtures(inmostcasesextractedfromplantoranimalsources).USESOFUSPREFERENCESTANDARDSTheofficialandauthorizedusesofUSPReferenceStandardsarespecifiedintheUSPmonographsandGeneralChaptersandtheyincludethefollowing:quantitativeusesinassaysfordrugsubstancesandformulations,limittests,orblanksandcontrolsqualitativeuses,suchasidentificationtests,systemsuitabilitytests,chromat