[Skip to Content](https://www.sigmaaldrich.com#main-content) [](https://www.sigmaaldrich.com/US/en) Products Cart0 USEN Products [Login / Register](https://www.sigmaaldrich.com/oidc-sign-in) [Order Lookup](https://www.sigmaaldrich.com/US/en/order-lookup) [Quick Order](https://www.sigmaaldrich.com/US/en/quick-order) Cart0 [Home](https://www.sigmaaldrich.com/US/en)[Applications](https://www.sigmaaldrich.com/US/en/applications)[Analytical Chemistry](https://www.sigmaaldrich.com/US/en/applications/analytical-chemistry)Calibration, Qualification & Validation # Calibration, Qualification & Validation  Reference materials are substances having homogenous and well-established values of one or more properties. They play a vital role in ensuring accuracy of measurements through method calibration, validation of a measurement method, estimation of measurement uncertainty, or assigning values to materials. They are a critical component of analytical testing workflows and broader quality assurance schemes. Manufactured under stringent requirements, reference materials differ from other lab reagents in their certification and traceability of the data provided. The world of reference materials is vast and includes Certified Reference Materials (CRMs) and other quality grades of reference materials and concepts like certificates of analysis and metrological traceability. * * * ## Related Products Slide 1 of 8 1 of 2 [ \ Supelco \ C-161 \ C-Peptide solution](https://www.sigmaaldrich.com/US/en/product/cerillian/c161) Quick View [ \ Supelco \ C-180 \ 7-Hydroxy cannabidiol (7-OH-CBD) solution](https://www.sigmaaldrich.com/US/en/product/cerillian/c180) Quick View [ \ Supelco \ 79601 \ 2-Hydroxy-3-(1*H*-1,2,4-triazol-1-yl)propanoic acid](https://www.sigmaaldrich.com/US/en/product/supelco/79601) Quick View [ \ Supelco \ 19041 \ Elemental Impurities according to ICH Q3D oral, Standard 1](https://www.sigmaaldrich.com/US/en/product/sial/19041) Quick View [ \ Supelco \ 95636 \ Extractables and Leachables Screening Standard for LC](https://www.sigmaaldrich.com/US/en/product/sial/95636) Quick View [ \ Supelco \ 39302 \ Okadaic acid solution](https://www.sigmaaldrich.com/US/en/product/sial/39302) Quick View [ \ NIST8671 \ NISTmAb, Humanized IgG1k Monoclonal Antibody](https://www.sigmaaldrich.com/US/en/product/sial/nist8671) Quick View [ \ Supelco \ PHR1084 \ Metformin hydrochloride](https://www.sigmaaldrich.com/US/en/product/sial/phr1084) Quick View * * * ## Featured Categories [](https://www.sigmaaldrich.com/US/en/products/analytical-chemistry/reference-materials/karl-fischer-standards) [Karl Fischer Standards](https://www.sigmaaldrich.com/US/en/products/analytical-chemistry/reference-materials/karl-fischer-standards) Easily determine water content in solids, liquids, gases using Aquastar® reagents. Accurate results with our water standards for titrations. [Shop Products](https://www.sigmaaldrich.com/US/en/products/analytical-chemistry/reference-materials/karl-fischer-standards) [](https://www.sigmaaldrich.com/US/en/products/analytical-chemistry/reference-materials/amino-acid-peptide-and-protein-standards) [Amino Acid, Peptide & Protein Standards](https://www.sigmaaldrich.com/US/en/products/analytical-chemistry/reference-materials/amino-acid-peptide-and-protein-standards) Our analytical standards of proteins, peptides, and amino acids offer accurate and reliable results in biomarker discovery, pharmaceutical research, clinical and diagnostic testing, top-down and bottom-up proteomics, and food authentication applications. [Shop Products](https://www.sigmaaldrich.com/US/en/products/analytical-chemistry/reference-materials/amino-acid-peptide-and-protein-standards) [](https://www.sigmaaldrich.com/US/en/products/analytical-chemistry/reference-materials/microbiology-standards) [Microbiology Standards](https://www.sigmaaldrich.com/US/en/products/analytical-chemistry/reference-materials/microbiology-standards) Explore certified microbiological reference materials: VITROIDS™, LENTICULE® discs by Supelco®. Ideal for food, beverage, cannabis testing. Order today. [Shop Products](https://www.sigmaaldrich.com/US/en/products/analytical-chemistry/reference-materials/microbiology-standards) * * * Overview Related Articles & Protocols Support Certified Reference Materials are indispensable for the exact titer determination in general and Karl Fischer Titrations. They are also important for the exact calibration of analytical instruments like pH meters, AAS – Atomic Absorption Spectrometers, ICP – Inductively Coupled Plasma Spectroscopy, HPLC – High Performance Liquid Chromatography, LC - Liquid Chromatography, GC- Gas Chromatography and IC – Ion Chromatography. Reference materials are a critical component of analytical testing workflows and broader quality assurance schemes. They are manufactured under stringent requirements and differ from other laboratory reagents in the certification and traceability of the data provided. From Certified Reference Materials (CRMs) and other quality grades of reference materials to certificates of analysis, metrological traceability, and other concepts, the world of reference materials is vast, and at times, confusing. Reference materials are classified into five major categories based on their quality grades, from national metrology and other primary standards to Certified Reference Materials (CRMs), Reference Materials (RMs), Analytical Standards, and research grade or research chemicals. The certification and traceability requirements increase from one quality grade to the higher one. The top-level is given standardization by the national governments, whereas specific ISO guidelines provide standardization for CRMs and RMs. These ISO requirements include ISO 17034, ISO/IEC 17025, and ISO Guide 31. Reference material producers must meet these ISO requirements to manufacture CRMs or RMs. For Certified Reference Materials, a Certificate of Analysis must be provided, and the information contained within is defined by the earlier mentioned ISO guidelines. The quality specifications for the last two levels are outlined by each independent producer rather than by a national government or ISO accreditations specific to CRMs and RMs.  __National Metrology Standard__ (e.g. NIST, JRC, NMI Australia) __Compendial Standard__ (e.g. USP, EP, BP, JP, IP) - Issued by an authorized body - Considered to provide the highest level of accuracy and traceability __Certified Reference Material__ (CRM) (ISO 17034, 17025) - Considered to provide the highest level of accuracy, uncertainty, and traceability to an SI unit of measurement - Manufactured by an accredited Reference Material Producer __Reference Material__ (RM) (ISO 17034) - Fulfilling ISO requirements which are less demanding than for CRMs - Manufactured by an accredited Reference Material Producer __Analytical Standard__ (ISO 9001) - Certificate of Analysis available - Level of certification varies __Reagent Grade / Research Chemical__ - May come with a Certificate of Analysis - Are not characterized for use as reference materials __Figure 2.__ The Hierarchy of Reference Materials - What Are the Different Types? Depending on the method requirements or product availability, reference materials are used in three different formats ‒ powder, solution, or matrix. Selection of the right reference material is of critical importance to a laboratory’s testing application, since results are only as accurate as the reference. ## Selection of reference materials based on testing purpose The qualification and calibration of instruments require the maintenance and establishment of its traceability. The selected reference material helps a laboratory to achieve this. In daily routine system suitability applications, it might be important to qualify a reference material which is practical and easy to use, yet reliable and cost-effective for everyday use. In method validation, the use of highly accurate and precise reference materials is critical to show that the laboratory method is accurate and precise. For identity and screening purposes, important attributes of reference materials include proven authenticity and identity. In applications involving quantitation, assays, or stability assessments stable and accurate reference materials are required. Type of TestUse of Ref. Mat.ExamplesRequirements of Ref. Material  Instrument Qualification/Calibration Establish system performance Measurement accuracyAnnual Qualifications Routine balance calibrationsTraceable  Routine Calibration/System SuitabilityDaily/Weekly System/Method Specific Establish Routine Performance  Pre-use balance calibrations System performance checks for LC-UV/MS; GC-FID...Qualify as suitable for use  Method ValidationAccuracy Precision Specificity & Interferences LOD/LOQ & LinearityPharma QC; Environmental testing Standards of the analyte(s), interferences, impuritiesAccurate Traceable  IdentityComparison of unknown to knownIncoming raw materials in pharma, food, etc. Screening testsAuthenticity  Content or AssayQuantitation of analytesPesticide/toxin limits Pharma QC - API contentCertifies content Traceable  Stability AssessmentMonitor product stabilityPharma QCStable, homogenous  Internal Quality ControlMethod accuracyRoutine quantitation of analytes - pharma/pesticides/diagnosticsCertified content Traceable  Table 1.Use for reference materials - type of test The selection of Fit-for-purpose reference materials can depend on several factors such as regulatory requirements, availability, type of testing application, level of accuracy, and sample matrix. | | | | | | | | | |------------------------------------------|--------------|---------------------|-----|----|---------------------|------------------|-------------------------------------------| | Type of Test | NMI Standard | Compendial Standard | CRM | RM | Analytical Standard | Reagent Chemical | Attribute | | Intrument Qualification / Calibration | ✓ | ✓ | ✓ | | | | Traceability & Accuracy | | Routine Calibration / System Suitability | ✓ | ✓ | ✓ | ✓ | Maybe | | Qualified Standard (Primary or Secondary) | | Method Validation | ✓ | ✓ | ✓ | ✓ | | | Accuracy, Precision, Bias | | Identitiy | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | Authenticity | | Content or Assay | ✓ | ✓ | ✓ | ✓ | Maybe | | Qualified Standard | | Stability Assessment | ✓ | ✓ | ✓ | ✓ | Maybe | | Qualified Standard | | Internal Quality Control | ✓ | ✓ | ✓ | ✓ | Maybe | | Qualified Standard | | Regulatory / Accreditation | ✓ | ✓ | ✓ | ✓ | | | Qualified Standard | Table 2.Fit for purpose guidance in standard selection [](https://www.sigmaaldrich.com/documents-search) [Looking for More Specific Information?](https://www.sigmaaldrich.com/documents-search) Visit our document search for data sheets, certificates and technical documentation. [Find Documents](https://www.sigmaaldrich.com/documents-search) ## Related Articles - [Elemental Impurities - Certified Ref. Materials](https://www.sigmaaldrich.com/US/en/technical-documents/technical-article/analytical-chemistry/calibration-qualification-and-validation/elemental-impurities) Control elemental impurities in drug products with analytical methods and materials to ensure patient safety. - [Choosing Correct Reference Material Quality Grade](https://www.sigmaaldrich.com/US/en/technical-documents/technical-article/analytical-chemistry/calibration-qualification-and-validation/how-to-choose-the-correct-reference-material-quality-grade) Reference materials, standards and certified reference materials are critical for analytical testing. We can help you to choose the ideal reference material for your application, whether you are using reference materials for calibration or quantitative analysis. - [Importance of Volumetric Solution Standardization](https://www.sigmaaldrich.com/US/en/technical-documents/technical-article/analytical-chemistry/calibration-qualification-and-validation/standardizationof-volumetric-solutions) The titer determination or standardization of a titration solution is essential for accurate and reliable titration results. - [NMR Reference Standards](https://www.sigmaaldrich.com/US/en/technical-documents/technical-article/analytical-chemistry/calibration-qualification-and-validation/nmr-reference-standards) NMR reference standards ensure proper instrument performance. Review key operational parameters for these standards such as pw90, sensitivity, resolution and line shape. - [Certified Reference Materials for ¹⁹F NMR](https://www.sigmaaldrich.com/US/en/technical-documents/technical-article/analytical-chemistry/calibration-qualification-and-validation/the-international-system-of-units) Introduction of 19F qNMR certified reference materials for complex molecule certification. - [See All (61)](https://www.sigmaaldrich.com/US/en/search/facet-search?focus=sitecontent&term=facet-search) ## Related Protocols - [FAME Standard for Optimizing GC System Performance](https://www.sigmaaldrich.com/US/en/technical-documents/protocol/analytical-chemistry/calibration-qualification-and-validation/fame-standard-for) FAME Standard for Optimizing GC System Performance - [Neonicotinoids](https://www.sigmaaldrich.com/US/en/technical-documents/protocol/analytical-chemistry/calibration-qualification-and-validation/neonicotinoids-bee-pesticides) Learn more about Neonicotinoids - active substances used in plant protection products to control harmful insects. - [Fast and Reliable Environmental Analysis of Aldehyde and Ketone Air Pollutants](https://www.sigmaaldrich.com/US/en/technical-documents/protocol/analytical-chemistry/calibration-qualification-and-validation/fast-and-reliable) Aldehydes and ketones are ubiquitous air pollutants. Along with esters and ethers, they are major components of indoor air pollution and are therefore important for industrial hygiene applications. - [Analysis of Alkylphenols Using New Internal Standards](https://www.sigmaaldrich.com/US/en/technical-documents/protocol/analytical-chemistry/calibration-qualification-and-validation/analysis-of-alkylphenols) Alkylphenols are used in various industries like paper manufacturing and pesticide formulations. - [Allergenic Fragrance Testing – Certified Materials](https://www.sigmaaldrich.com/US/en/technical-documents/protocol/analytical-chemistry/calibration-qualification-and-validation/allergenic-fragrance-testing) IFRA method introduces new CRMs for allergenic fragrances, analyzed by GC with ionic liquid capillary column for selectivity. - [See All (62)](https://www.sigmaaldrich.com/US/en/search/facet-search?focus=sitecontent&term=facet-search) ### Find More Articles and Protocols Enter Keywords Search ## How Can We Help In case of any questions, please submit a [customer support request](https://www.sigmaaldrich.com/US/en/support/customer-support) or talk to our customer service team: Email [[email protected]](mailto:[email protected]) or call +1 (800) 244-1173 ## Additional Support - [Chromatogram Search](https://www.sigmaaldrich.com/chromatogram-search) Use the Chromatogram Search to identify unknown compounds in your sample. - [Calculators & Apps](https://www.sigmaaldrich.com/US/en/support/calculators-and-apps) Web Toolbox - science research tools and resources for analytical chemistry, life science, chemical synthesis and materials science. - [Customer Support Request](https://www.sigmaaldrich.com/US/en/support/customer-support) Customer support including help with orders, products, accounts, and website technical issues. - [FAQ](https://maestro.my.site.com/knowledgeportal/s/) Explore our Frequently Asked Questions for answers to commonly asked questions about our products and services. * * * __Featured Articles__ [Elemental Impurities - Certified Ref. Materials](https://www.sigmaaldrich.com/US/en/technical-documents/technical-article/analytical-chemistry/calibration-qualification-and-validation/elemental-impurities) Control elemental impurities in drug products with analytical methods and materials to ensure patient safety. [Choosing Correct Reference Material Quality Grade](https://www.sigmaaldrich.com/US/en/technical-documents/technical-article/analytical-chemistry/calibration-qualification-and-validation/how-to-choose-the-correct-reference-material-quality-grade) Reference materials, standards and certified reference materials are critical for analytical testing. We can help you to choose the ideal reference material for your application, whether you are using reference materials for calibration or quantitative analysis. [Importance of Volumetric Solution Standardization](https://www.sigmaaldrich.com/US/en/technical-documents/technical-article/analytical-chemistry/calibration-qualification-and-validation/standardizationof-volumetric-solutions) The titer determination or standardization of a titration solution is essential for accurate and reliable titration results. [NMR Reference Standards](https://www.sigmaaldrich.com/US/en/technical-documents/technical-article/analytical-chemistry/calibration-qualification-and-validation/nmr-reference-standards) NMR reference standards ensure proper instrument performance. Review key operational parameters for these standards such as pw90, sensitivity, resolution and line shape. Top __Sign In To Continue__ To continue reading please sign in or create an account. Sign In__Don't Have An Account?__Register An unknown error has occured. - English - EN - Español - ES [Learn More](https://www.sigmaaldrich.com)