á11ñUSP REFERENCE STANDARDS
USP Reference Standards are established and released under the authority of the USPC Board of Trustees upon recommendation of the USP Reference Standards Committee,which passes on the selection and suitability of each lot.The critical characteristics of each lot of specimen selected for the standard are usually determined independently in three or more laboratories.The USP Reference Standards Laboratory (see Preface)and the FDAlaboratories participate in testing almost all new Standards and replacements for existing Standards.In addition,laboratories throughout the nation,both academic and industrial,participate in the testing.
Reference Standards are specifically required in many Pharmacopeial assays and tests and are provided solely for such use;suitability for other nonofficial application(s)rests with the purchaser.Originally introduced for the biological assays of USP X,reference standards are now required for numerous other procedures as well.This reflects the extensive use of modern chromatographic and spectrophotometric methods,which require measurements relative to a reference standard to attain accurate and reproducible results.
USP Reference Standards are substances selected for their high purity,critical characteristics,and suitability for the intended purpose.Heterogeneous substances,of natural origin,also are designated Reference Standardswhere needed.Usually these are the counterparts of international standards.
Antibiotic reference standards distributed by the USPChave been designated by the FDAas identical to FDAworking standards under the FDAprocedures.USPCdistributes both U.S.Reference Standards and USP Reference Standards for antibiotic substances.This difference in labeling the Standards is in effect only temporarily,and eventually all vials will bear the same title.Where a USP Reference Standard is called for,the corresponding substance labeled as a U.S.Reference Standardmay be used,and vice versa.
Reference Standards currently labeled as NF Reference Standardswill eventually all be designated and labeled as USP Reference Standardspursuant to the consolidation of USPand NFwithin the USPCas of January 2,1975.Meanwhile,where a USP Reference Standard is called for,the corresponding substance labeled as an NF Reference Standardmay be used.
Authentic Visual Reference
Unlike chemical reference standards,Authentic Visual References (AVRs)are not used in chemical analysis.Instead,the AVRs are visual images used by analysts to compare certain test articles to ensure that they meet compendial requirements and are incorporated by reference into the monograph.Approval of AVRs for use in a monograph is the decision of the Expert Committee that approves the specific monograph.
Other Reference Substances
As a service,the USPCtests and distributes additional authenticated substances not currently required as USPor NF Reference Standards.These also are provided under the supervision of the USP Reference Standards Committee.These additional substances fall into three groups:(1)former USPand NF Reference Standards,not required in the current USPor NFbut for which sufficient demand remains;(2)FCC Reference Standards,specified in the current edition of the Food Chemicals Codex;and (3)Authentic Substances (AS),which are highly purified samples of chemicals,including substances of abuse,that are collaboratively tested and made available as a service primarily to analytical,clinical,pharmaceutical,and research laboratories.
The distribution of controlled substances is subject to the regulations and licensing provisions of the Drug Enforcement Administration of the Department of Justice.
As an additional service,the USPCdistributes several non-commercial reagents required in certain USPmonographs.These reagents are specially prepared for their intended use and will be distributed by USPConly until they become commercially available.
Aprogram to provide international biological standards and chemical reference substances is maintained by the World Health Organization,an agency of the United Nations.The WHOprogram is concerned with reference materials for antibiotics,biologicals,and chemotherapeutic agents.As a rule,an International Standard for a material of natural origin is discontinued once the substance responsible for its characteristic activity has been isolated,identified,and prepared in such form that it can be completely characterized by chemical and physical means.The USP Reference Standards Committee collaborates closely with the WHOin order to minimize unavoidable differences in the actual units of potency,and in some cases to share in the preparation of a reference standard.Since some USP Reference Standards are standardized in terms of the corresponding International Standards,the relevant USP Units and the International Units of potency are generally identical.
It is the responsibility of each analyst to ascertain that his particular supply of USP Reference Standard is current.Only sufficient quantity for immediate use should be purchased,and long-term storage should be avoided.
To ensure ready access to the latest information,the USPCpublishes the Official Catalog of Reference Standards and Authentic Substances,and the lot designations,bimonthly in Pharmacopeial Forum.*This system offers more positive control and flexibility in responding to revisions in Reference Standard usage than would expiration dates.The Catalog in the most recent Pharmacopeial Forumidentifies items that are official in the USP Reference Standards collection at the time of publication.
Two columns appear in the Catalog to identify the current official lots.One column identifies the official lot currently being shipped by USPC.In some cases,the previous lot may still be considered official.If so,it is identified in the second column.Ordinarily the previous lot is carried in official status for about one year after the current lot entered distribution unless,because of a change in monograph requirements or stability limitations,the previous lot is found to be no longer suitable.
PROPER USE OF USP REFERENCE STANDARDS
Unless a Reference Standard label states a specific potency or content,the Reference Standard is taken as being 100.0%pure for compendial purposes.The suitability of a USP Reference Standard for noncompendial application is left up to the user.
To serve its intended purpose,each USP Reference Standard must be properly stored,handled,and used.Generally,Reference Standards should be stored in their original stoppered containers away from heat and protected from light.Avoid humid storage areas in particular.Where special storage conditions are necessary,directions are given on the label.
Neither Reference Standards nor Authentic Substances are intended for use as drugs or as medical devices.
Many Pharmacopeial tests and assays are based on comparison of a test specimen with a USP Reference Standard.In such cases,measurements are made on preparations of both the test specimen and the Reference Standard.Where it is directed that a Standard solution or a Standard preparationbe prepared for a quantitative determination by stepwise dilution or otherwise,it is intended that the Reference Standard substance shall be accurately weighed (see Weights and Balances á41ñand Volumetric Apparatus á31ñ).Due account should also be taken of the relatively large errors associated with weighing small masses (see also Dilutionunder Tests and Assaysin the General Notices and Requirements).
Assay and test results are determined on the basis of comparisons of the specimen under test with a USP Reference Standard that has been freed from or corrected for volatile residues or water content as instructed on the label.Where special drying requirements for Reference Standards are found in specific sections ofUSPor NFmonographs,those supersede the usual instructions (see Proceduresunder Tests and Assaysin the General Notices and Requirements).Where a USP Reference Standard is required to be dried before using,transfer an amount,sufficient after drying,to a clean and dry vessel.Do not use the original container as the drying vessel,and do not dry a specimen repeatedly at temperatures above 25.Where the titrimetric determination of water is required at the time a Reference Standard is to be used,proceed as directed for Method Iunder Water Determination á921ñ.Instrumental or microanalytical methods are acceptable for this purpose.When using typical amounts,about 50mg,of the Reference Standard,titrate with a fourfold dilution of the Reagent.
The USP Reference standardssection of an individual USPor NFmonograph or general chapter names each USP Reference Standard required for assay and test procedures and refers to this chapter for additional information and instructions.The list that follows presents the instructions for the proper use and storage of each required USP Reference Standard.These instructions are to be the same as those appearing on the corresponding USP Reference Standard label.Where,in an isolated instance,the specific label instruction differs from the text in the following list,the instruction on the label of the item from the current lot takes precedence.Asituation may be infrequently encountered where it is necessary,on scientific grounds,to effect immediately a change in the instructions.This change can be made easily on the label of the Reference Standard,whereas the formal process for revising the compendial text requires more time.Thus,it is especially important to refer to the current Supplement to USPand to NFfor official revisions to the following list.
USP REFERENCE STANDARDS SPECIFIED IN USP AND NF MONOGRAPHS AND GENERAL CHAPTERS
NOTEConsult the latest Supplement or Interim Revision AnnouncementPertaining to USPand to NFfor revisions,additions,or deletions.
Revisions,additions,and deletions of individual USP Reference Standards are listed cumulatively in each Supplement to USPNF.As a consequence,therefore,it is necessary to consult only USP28NF23and the latest Supplement for the complete list of USP Reference Standards currently specified in USPNFmonographs and general chapters.The list provides up-to-date and complete names,applicable chemical information,and handling instructions for the USP Reference Standards that are in distribution as of the official date of that Supplement.
Revisions of this chapter are implemented continuously via the Interim Revision Announcementsthat are published in Pharmacopeial Forum.Those interim revisions of USP Reference Standards are cumulatively included in the next USPNFSupplement.
The alphabetical list that follows constitutes an index of all revisions to this chapter.Thus,it is unnecessary to name repetitively the revised Reference Standards in the general index to the Supplement.
In the list that follows,chemical names are given for many substances (e.g.,related compounds)that are not USPor NFmonograph articles.Following the name of such a chemical substance RS,the empirical formula and molecular weight,separated by the symbol,may be given in parentheses if those data are available.
* For nonsubscribers,the most recent Official Catalog is available from:U.S.Pharmacopeial Convention,Inc.,Reference Standards Order Department,12601Twinbrook Parkway,Rockville,MD20852.Telephone 1-301-881-0666.FAX1-301-816-8148.Toll-free telephone 1-800-227-USPCor access the Catalog on USP's web site store.usp.org.