1、INTRODUCTION簡介Thisdocumentiscomplementarytotheparentdocument,whichpresentsadiscussionofthecharacteristicsthatshouldbeconsideredduringthevalidationofanalyticalprocedures.Itspurposeistoprovidesomeguidanceandrecommendationsonhowtoconsiderthevariousvalidationcharacteristicsforeachanalyticalprocedure.Ins

2、omecases(forexample,demonstrationofspecificity),theoverallcapabilitiesofanumberofanalyticalproceduresincombinationmaybeinvestigatedinordertoensurethequalityofthedrugsubstanceordrugproduct.Inaddition,thedocumentprovidesanindicationofthedata,whichshouldbepresentedinaregistrationapplication.本文作為前文的補充，旨

3、在討論在分析方法驗證過程中在每一個具體的項目需要考慮哪些內容。本文的目的是就不同類型的驗證該涵蓋哪些項目提供一個指導原則和建議。以專屬性為例，為了確保原料藥或制劑的質量，需要考察分析過程對化合物中雜質的全面綜合分析能力。另外，文件提供的數據應該包含在注冊申請材料中。Allrelevantdatacollectedduringvalidationandformulaeusedforcalculatingvalidationcharacteristicsshouldbesubmittedanddiscussedasappropriate.驗證報告中的所有數據及每個驗證項目的計算公式應一同提交并進行

4、適當的論述(即得出相應結論)OApproachesotherthanthosesetforthinthisguidelinemaybeapplicableandacceptable.Itistheresponsibilityoftheapplicanttochoosethevalidationprocedureandprotocolmostsuitablefortheirproduct.Howeveritisimportanttorememberthatthemainobjectiveofvalidationofananalyticalprocedureistodemonstratethatt

5、heprocedureissuitableforitsintendedpurpose.Duetotheircomplexnature,analyticalproceduresforbiologicalandbiotechnologicalproductsinsomecasesmaybeapproacheddifferentlythaninthisdocument.本文闡述的原則之外的原則應該適用并可接受。申請者的職責是制定最適合申報產品的驗證項目及驗證方案。最重要的是記住分析方法驗證的主要目的是證明該分析程序能達到預期目標。由于生物制品和生物科技產品本身的復雜性，有時候，其分析方法的驗證也可能

6、與本文提到的方法不同。Well-characterizedreferencematerials,withdocumentedpurity,shouldbeusedthroughoutthevalidationstudy.Thedegreeofpuritynecessarydependsontheintendeduse.驗證研究用到的參比物質需要經過完全鑒定并標定純度。所需的純度取決于其應用類型(預期用途)。Inaccordancewiththeparentdocument,andforthesakeofclarity,thisdocumentconsidersthevariousvalidat

7、ioncharacteristicsindistinctsections.Thearrangementofthesesectionsreflectstheprocessbywhichananalyticalproceduremaybedevelopedandevaluated.與前文相同，該文件考慮了各個獨立章節的不同驗證項目。這些章節的安排也反映了分析方法的建立和評估的過程。Inpractice,itisusuallypossibletodesigntheexperimentalworksuchthattheappropriatevalidationcharacteristicscanbec

8、onsideredsimultaneouslytoprovideasound,overallknowledgeofthecapabilitiesoftheanalyticalprocedure,forinstance:specificity,linearity,range,accuracyandprecision.事實上，設計試驗的時候，一些適當的驗證項目可以同時考慮，以便對分析方法的能力提供合理的，全面的了解(依據)，例如：專屬性、線性、范圍、準確度、精密度。providea,knowledgeof為,，提供依據1. SPECIFICITY專屬性Aninvestigationofspecif

9、icityshouldbeconductedduringthevalidationofidentificationtests,thedeterminationofimpuritiesandtheassay.Theproceduresusedtodemonstratespecificitywilldependontheintendedobjectiveoftheanalyticalprocedure.鑒別測試、雜質和含量測試方法的驗證都應考察方法的專屬性。證明專屬性的方法取決于分析方法的預期目的。Itisnotalwayspossibletodemonstratethatananalytical

10、procedureisspecificforaparticularanalyte(completediscrimination).InthiscaseacombinationoftwoormorePage2of17analyticalproceduresisrecommendedtoachievethenecessarylevelofdiscrimination.一般來說，某一種分析方法不太可能完全證明其對某一特定被分析物具有專屬性。這種情況下，建議采用兩種或兩種以上的分析方法以確保完全鑒別水平。1.1. Identification鑒另Suitableidentificationtestss

11、houldbeabletodiscriminatebetweencompoundsofcloselyrelatedstructures,whicharelikelytobepresent.Thediscriminationofaproceduremaybeconfirmedbyobtainingpositiveresults(perhapsbycomparisonwithaknownreferencematerial)fromsamplescontainingtheanalyte,coupledwithnegativeresultsfromsamples,whichdonotcontainth

12、eanalyte.Inaddition,theidentificationtestmaybeappliedtomaterialsstructurallysimilartoorcloselyrelatedtotheanalytetoconfirmthatapositiveresponseisnotobtained.Thechoiceofsuchpotentiallyinterferingmaterialsshouldbebasedonsoundscientificjudgmentwithaconsiderationoftheinterferencesthatcouldoccur.合適的鑒別方法應

13、該能夠區分可能存在的結構相近的化合物。可以同已知參考物質進行比較，從含有被分析物的樣品得到的正的結果和不含被分析物的樣品得到的負的結果來確定。止匕外，鑒別測試也可以用結構相近或相關的物質測試得不到正的反應來證實。在考慮可能會造城干擾的前提下，應根據合理科學的判斷來選擇可能存在的干擾物。likelytobepresent:可能存在的；discrimination:比較；1.2. AssayandImpurityTest(s)含量和雜質測定Forchromatographicprocedures,representativechromatogramsshouldbeusedtodemonstrat

14、especificityandindividualcomponentsshouldbeappropriatelylabelled.Similarconsiderationsshouldbegiventootherseparationtechniques.在色譜法測定中，需要用有代表性的圖譜證明專屬性，并恰當的注明每一個成分。其它的分離技術也應如此。Criticalseparationsinchromatographyshouldbeinvestigatedatanappropriatelevel.Forcriticalseparations,specificitycanbedemonstrat

15、edbytheresolutionofthetwocomponents,whicheluteclosesttoeachother.色譜分離法應在一定程度上考察關鍵性的分離。對關鍵性的分離，可用兩個洗脫程度最接近的化合物的分離度來證明其專屬性。Incaseswhereanon-specificassayisused,othersupportinganalyticalproceduresshouldbeusedtodemonstrateoverallspecificity.Forexample,whereatitrationisadoptedtoassaythedrugsubstanceforre

16、lease,thecombinationoftheassayandasuitabletestforimpuritiescanbeused.當采用非專屬性的方法測定含量時，應采用輔助性分析方法來證明整個方法具有專屬性。例如用滴定法測定放行原料藥的含量，可結合使用合適的雜質檢測方法。supportinganalyticalprocedures:輔助性分析方法；overallspecificity:整體專屬性；combination:結合，聯合；Theapproachissimilarforbothassayandimpuritytests:下述方法均適用于含量和雜質檢測。issimilarfor:

17、適用于1.2.1 Impuritiesareavailable可以得到雜質的情況Fortheassay,thisshouldinvolvedemonstrationofthediscriminationoftheanalyteinthepresenceofimpuritiesand/orexcipients;practically,thiscanbedonebyspikingpuresubstances(drugsubstanceordrugproduct)withappropriatelevelsofimpuritiesand/orexcipientsanddemonstratingthat

18、theassayresultisunaffectedbythepresenceofthesematerials(bycomparisonwiththeassayresultobtainedonunspikedsamples).對含量檢測，專屬性應該包括提供被分析物在雜質和/或賦形劑存在時能被區分的證明；實際操作時，可通過向純物質(原料藥或制劑)中加入一定量的雜質和/或賦形劑的檢測結果和未添加雜質和/或賦形劑的純物質的檢測結果進行對比以此證明這些雜質和/或賦形劑的存在不會對含量檢測結果造成影響。discrimination:區分Fortheimpuritytest,thediscriminati

19、onmaybeestablishedbyspikingdrugsubstanceordrugproductwithappropriatelevelsofimpuritiesanddemonstratingtheseparationofPage4of17theseimpuritiesindividuallyand/orfromothercomponentsinthesamplematrix.對雜質檢測，可以向原料藥或制劑中加入一定量的雜質，證明各雜質能夠分離且能與樣品中的其它組分分離。1.2.2 Impuritiesarenotavailable無法得到雜質的情況Ifimpurityordegr

20、adationproductstandardsareunavailable,specificitymaybedemonstratedbycomparingthetestresultsofsamplescontainingimpuritiesordegradationproductstoasecondwell-characterizedproceduree.g.:pharmacopoeialmethodorothervalidatedanalyticalprocedure(independentprocedure).Asappropriate,thisshouldincludesamplesst

21、oredunderrelevantstressconditions:light,heat,humidity,acid/basehydrolysisandoxidation.如果無法得到雜質或降解產物的對照品，檢測方法的專屬性可以通過將含有一定量的雜質或降解產物的樣品的檢測結果與另一種成熟的檢測方法一一如藥典方法或經驗證的其它方法(獨立的方法)一一的檢測結果進行比較來證明。必要時，應該包括放置在強降解試驗條件，即強光，高溫，高濕，酸/堿水解及氧化條件下的樣品測試。Asappropriate:必要時；- Fortheassay,thetworesultsshouldbecompared;- 對含量

22、檢測，需要對比兩種方法的檢測結果- Fortheimpuritytests,theimpurityprofilesshouldbecompared.- 對雜質檢測，需要對比雜質概況Peakpuritytestsmaybeusefultoshowthattheanalytechromatographicpeakisnotattributabletomorethanonecomponent(e.g.,diodearray,massspectrometry).峰純度測試是非常有用的，它能顯示被測物的色譜峰是一個成分還是多個成分(如二極管陣列，質譜)。2. LINEARITY線性Alinearrela

23、tionshipshouldbeevaluatedacrosstherange(seesection3)oftheanalyticalprocedure.Itmaybedemonstrateddirectlyonthedrugsubstance(bydilutionofastandardstocksolution)and/orseparateweighingsofsyntheticmixturesofthedrugproductcomponents,usingtheproposedprocedure.Thelatteraspectcanbestudiedduringinvestigationo

24、ftherange.檢測方法的線性關系應該在范圍內(見章節3)進行評價。線性研究可通過所建議的分析方法，直接對原料藥(用標準儲備液稀釋)和/或分別稱取制劑組分的混合物測試來進行。后者應在方法的范圍內進行研究。Linearityshouldbeevaluatedbyvisualinspectionofaplotofsignalsasafunctionofanalyteconcentrationorcontent.Ifthereisalinearrelationship,testresultsshouldbeevaluatedbyappropriatestatisticalmethods,fore

25、xample,bycalculationofaregressionlinebythemethodofleastsquares.Insomecases,toobtainlinearitybetweenassaysandsampleconcentrations,thetestdatamayneedtobesubjectedtoamathematicaltransformationpriortotheregressionanalysis.Datafromtheregressionlineitselfmaybehelpfultoprovidemathematicalestimatesofthedegr

26、eeoflinearity.線性應關系應以信號對被測物濃度或含量作圖，根據圖形是否呈線性來評估。如果呈線性關系，測試結果應用適當的統計學方法進行評估，例如用最小二乘法進行線性回歸計算。在某些情況下，為了使含量與樣品濃度呈線性關系，在回歸分析前需要對測試數據進行數學轉化。由線性回歸評估所得的數據本身又有助于精確的評價線性的程度。Insomecases:在某些情況下，有時候；Thecorrelationcoefficient,y-intercept,slopeoftheregressionlineandresidualsumofsquaresshouldbesubmitted.Aplotofthe

27、datashouldbeincluded.Inaddition,ananalysisofthedeviationoftheactualdatapointsfromtheregressionlinemayalsobehelpfulforevaluatinglinearity.相關系數，y軸上的截距，回歸曲線的斜率以及剩余方差應包含在遞交材料里。還應包括數據圖表。另外，實際數據點與回歸曲線的偏差也有助于對線性進行評價。Someanalyticalprocedures,suchasimmunoassays,donotdemonstratelinearityafteranytransformation

28、.Inthiscase,theanalyticalresponseshouldbedescribedbyanappropriatefunctionoftheconcentration(amount)ofananalyteinasample.一些分析方法，如免疫測定法，在任何轉換后，均不能證明呈線性。在這種情況下，分析的相應值應用被分析物的濃度(數量)的適當函數來表示。Fortheestablishmentoflinearity,aminimumof5concentrationsisrecommended.Otherapproachesshouldbejustified.為建立線性，建議至少用5

29、個濃度。若用其他方法應證明其合理性。3. RANGE范圍Thespecifiedrangeisnormallyderivedfromlinearitystudiesanddependsontheintendedapplicationoftheprocedure.Itisestablishedbyconfirmingthattheanalyticalprocedureprovidesanacceptabledegreeoflinearity,accuracyandprecisionwhenappliedtosamplescontainingamountsofanalytewithinoratth

30、eextremesofthespecifiedrangeoftheanalyticalprocedure.特定的范圍一般是從線性研究中得到的，它依賴于分析方法的應用目的。確定范圍的方法是：樣品中含有被分析物的量在分析方法規定的范圍內或在范圍末端，該分析方法均能獲得良好的線性，精密度及準確度。Thefollowingminimumspecifiedrangesshouldbeconsidered:以下是應考慮的最小規定范圍：- fortheassayofadrugsubstanceorafinished(drug)product:normallyfrom80to120percentofthete

31、stconcentration;- 對原料藥或成品藥(制劑)的含量測定：一般應在測試濃度的80%120%;- forcontentuniformity,coveringaminimumof70to130percentofthetestconcentration,unlessawidermoreappropriaterange,basedonthenatureofthedosageform(e.g.,metereddoseinhalers),isjustified;- 對含量均勻度檢測：應至少在測試濃度的70%130%之內，超出此范圍，應有正當理由，主要是根據劑型的特點(如定量吸入劑)；- fo

32、rdissolutiontesting:+/-20%overthespecifiedrange;- 對溶出度測試，應為規定范圍的+/-20%;e.g.,ifthespecificationsforacontrolledreleasedproductcoveraregionfrom20%,after1hour,upto90%,after24hours,thevalidatedrangewouldbe0-110%ofthelabelclaim.例如：如果是控釋劑，規定1小時后達到20%,24小時后達到90%,它的驗證范圍應為標示量的0110%。- forthedeterminationofanim

33、purity:fromthereportinglevelofanimpurity1to120%ofthespecification;- 對雜質測定，應為雜質的報告水平至標準規定的120%;- forimpuritiesknowntobeunusuallypotentortoproducetoxicorunexpectedpharmacologicaleffects,thedetection/quantitationlimitshouldbecommensuratewiththelevelatwhichtheimpuritiesmustbecontrolled;- 對已知有異常功效的，有毒的或者

34、有意外藥理作用的雜質，其檢測限度和定量限度應與該雜質必須被控制的水平相當。Note:forvalidationofimpuritytestprocedurescarriedoutduringdevelopment,itmaybenecessarytoconsidertherangearoundasuggested(probable)limit.注意：在研制階段進行雜質檢測方法驗證時，有必要根據建議(可能)的限度水平來考慮范圍；- ifassayandpurityareperformedtogetherasonetestandonlya100%standardisused,linearitysh

35、ouldcovertherangefromthereportingleveloftheimpurities1to120%oftheassayspecification.1seechapters"ReportingImpurityContentofBatches“ofthecorrespondingICH-Guidelines:"ImpuritiesinNewDrugSubstances”and“ImpuritiesinNewDrugProducts-如果一個試驗同時進行含量和純度檢測，且僅使用100%的標準品，線性范圍應覆蓋雜質的報告水平（見相應ICH指南"新原料

36、藥中的雜質”和“新制劑中的雜質”中“批雜質含量的報告”章節）至含量指標120%。4. ACCURACY準確度Accuracyshouldbeestablishedacrossthespecifiedrangeoftheanalyticalprocedure.應在分析方法規定的范圍內建立（考察方法的）準確度。4.1. Assay含量4.1.1 DrugSubstance原料藥Severalmethodsofdeterminingaccuracyareavailable:以下幾種方法可用于測定準確度：a) applicationofananalyticalproceduretoananalyteo

37、fknownpurity（e.g.referencematerial）;用該分析方法測定已知純度的被分析物（例如參照物質）；b) comparisonoftheresultsoftheproposedanalyticalprocedurewiththoseofasecondwell-characterizedprocedure,theaccuracyofwhichisstatedand/ordefined(independentprocedure,see1.2.);用建議采用的分析方法的結果與另一種完全驗證過的方法的結果作對比，對比的方法的準確度是規定的(一定的)和/或已定義的(獨立的方法，見

38、1.2節)c) accuracymaybeinferredonceprecision,linearityandspecificityhavebeenestablished.準確度可以在精密度，線性及專屬性建立之后推論得到；4.1.2 DrugProduct制劑Severalmethodsfordeterminingaccuracyareavailable:以下幾種方法可用于測定準確度：a) applicationoftheanalyticalproceduretosyntheticmixturesofthedrugproductcomponentstowhichknownquantitieso

39、fthedrugsubstancetobeanalysedhavebeenadded;用該分析方法測定按處方量制成的混合物，其中加入了已知量的待測原料藥。b) incaseswhereitisimpossibletoobtainsamplesofalldrugproductcomponents,itmaybeacceptableeithertoaddknownquantitiesoftheanalytetothedrugproductortocomparetheresultsobtainedfromasecond,wellcharacterizedprocedure,theaccuracyof

40、whichisstatedand/ordefined(independentprocedure,see1.2.);如果不能得到制劑的所有成分，向制劑中加入已知量的被測物或者與另一種經過完整驗證過的準確度是規定的(一定的)和/或已定義的方法的結果作對比，(獨立的方法，見1.2節)也是可以接受的；c) accuracymaybeinferredonceprecision,linearityandspecificityhavebeenestablished.準確度可以在精密度，線性及專屬性建立之后推論得到；4.2. Impurities(Quantitation)雜質(定量)Accuracyshou

41、ldbeassessedonsamples(drugsubstance/drugproduct)spikedwithknownamountsofimpurities.準確度可以通過向樣品(原料藥/制齊J)中加入已知量雜質的方法來評價。Incaseswhereitisimpossibletoobtainsamplesofcertainimpuritiesand/ordegradationproducts,itisconsideredacceptabletocompareresultsobtainedbyanindependentprocedure(see1.2.).Theresponsefact

42、orofthedrugsubstancecanbeused.如果無法得到雜質和或降解產物的樣品，可以通過與其它獨立方法(見1.2節)的檢測結果進行對比評估其準確度。可以使用原料藥的響應因子。Itshouldbeclearhowtheindividualortotalimpuritiesaretobedeterminede.g.,weight/weightorareapercent,inallcaseswithrespecttothemajoranalyte.需要說明單雜和總雜是如何測定的，如相對于主要被分析物所占的質量分數或面積百分比。4.3. RecommendedData可接受數據(數據要

43、求)Accuracyshouldbeassessedusingaminimumof9determinationsoveraminimumof3concentrationlevelscoveringthespecifiedrange(e.g.,3concentrations/3replicateseachofthetotalanalyticalprocedure).準確度的評價需要在方法的線性范圍內的三種濃度至少測定九次(按完整分析步驟對三種濃度每種濃度重復進樣三次)。Accuracyshouldbereportedaspercentrecoverybytheassayofknownaddeda

44、mountofanalyteinthesampleorasthedifferencebetweenthemeanandtheacceptedtruevaluetogetherwiththeconfidenceintervals.準確度應以向樣品中加入已知量的被測物所得的百分回收率或者平均值和可接受真實值之間的差值及置信區間來報告。5. PRECISION精密度Validationoftestsforassayandforquantitativedeterminationofimpuritiesincludesaninvestigationofprecision.含量和雜質的定量分析需要考察方法

45、的精密度。5.1. Repeatability重復性Repeatabilityshouldbeassessedusing:重復性可以通過以下方法進行考察：a) aminimumof9determinationscoveringthespecifiedrangefortheprocedure(e.g.,3concentrations/3replicateseach);在方法的線性范圍內至少檢測九次(三種濃度每種濃度重復進樣三次)；b) oraminimumof6determinationsat100%ofthetestconcentration.以100%測試濃度至少檢測六次。5.2. Inte

46、rmediatePrecision中間精密度Theextent(程度)towhichintermediateprecisionshouldbeestablisheddependsonthecircumstancesunderwhichtheprocedureisintendedtobeused.Theapplicantshouldestablishtheeffectsofrandomeventsontheprecisionoftheanalyticalprocedure.Typicalvariationstobestudiedincludedays,analysts,equipment,etc

47、.Itisnotconsiderednecessarytostudytheseeffectsindividually.Theuseofanexperimentaldesign(matrix)isencouraged.中間精密度的考察程度應根據分析方法的操作環境而定。申請者應確定(弄清楚)隨機時間對分析方法的精密度的影響。需要研究的典型變化有：日期，分析者，儀器等。沒有必要逐項考察這些因素。建議使用試驗設計（矩陣法）5.3. Reproducibility重現性Reproducibilityisassessedbymeansof（通過）aninter-laboratorytrial.Reprod

48、ucibilityshouldbeconsideredincaseofthestandardizationofananalyticalprocedure,forinstance,forinclusionofproceduresinpharmacopoeias.Thesedataarenotpartofthemarketingauthorizationdossier.重現性可通過實驗室之間的試驗進行評估。如果方法需要標準化，例如藥典方法，則應考慮重現性。這些資料不是上市申請文檔的一部分（申報注冊不需要考察藥典收錄方法的重現性，這是藥典委需要考慮的問題）。5.4. RecommendedData數

49、據要求Thestandarddeviation,relativestandarddeviation（coefficientofvariation）andconfidenceintervalshouldbereportedforeachtypeofprecisioninvestigated.每一種精密度研究中都應報告標準偏差，相對標準偏差（變異系數）和置信區問。6. DETECTIONLIMIT檢測限Severalapproachesfordeterminingthedetectionlimitarepossible,dependingonwhethertheprocedureisanon-in

50、strumentalorinstrumental.Approachesotherthanthoselistedbelowmaybeacceptable.根據檢測方法是用儀器分析還是非儀器分析，可用幾種方法來確定檢測限。除了下面所列的方法外，其它的分析方法也可能被接收。6.1. .BasedonVisualEvaluation視覺判定（根據直觀評價）Visualevaluationmaybeusedfornon-instrumentalmethodsbutmayalsobeusedwithinstrumentalmethods.視覺判定可用于非儀器分析方法，也可用于儀器分析方法。Thedetec

51、tionlimitisdeterminedbytheanalysisofsampleswithknownconcentrationsofanalyteandbyestablishingtheminimumlevelatwhichtheanalytecanbereliablydetected.檢測限的確定是通過一系列已知濃度的分析物樣品進行分析，并以能準確測得被分析物的最小水平來建立。6.2. .BasedonSignal-to-NoiseThisapproachcanonlybeappliedtoanalyticalprocedureswhichexhibitbaselinenoise.Det

52、erminationofthesignal-to-noiseratioisperformedbycomparingmeasuredsignalsfromsampleswithknownlowconcentrationsofanalytewiththoseofblanksamplesandestablishingtheminimumconcentrationatwhichtheanalytecanbereliablydetected.Asignal-to-noiseratiobetween3or2:1isgenerallyconsideredacceptableforestimatingthed

53、etectionlimit.6.3. BasedontheStandardDeviationoftheResponseandtheSlopeThedetectionlimit(DL)maybeexpressedas:3.3(TDL=Swhereo-=hestandarddeviationoftheresponseS=theslopeofthecalibrationcurveTheslopeSmaybeestimatedfromthecalibrationcurveoftheanalyte.Theestimateofsmaybecarriedoutinavarietyofways,forexam

54、ple:6.3.1 BasedontheStandardDeviationoftheBlankMeasurementofthemagnitudeofanalyticalbackgroundresponseisperformedbyanalyzinganappropriatenumberofblanksamplesandcalculatingthestandarddeviationoftheseresponses.6.3.2 BasedontheCalibrationCurveAspecificcalibrationcurveshouldbestudiedusingsamplescontaini

55、ngananalyteintherangeofDL.Theresidualstandarddeviationofaregressionlineorthestandarddeviationofy-interceptsofregressionlinesmaybeusedasthestandarddeviation.6.4. RecommendedDataThedetectionlimitandthemethodusedfordeterminingthedetectionlimitshouldbepresented.IfDLisdeterminedbasedonvisualevaluationorb

56、asedonsignaltonoiseratio,thepresentationoftherelevantchromatogramsisconsideredacceptableforjustification.Incaseswhereanestimatedvalueforthedetectionlimitisobtainedbycalculationorextrapolation,thisestimatemaysubsequentlybevalidatedbytheindependentanalysisofasuitablenumberofsamplesknowntobenearorprepa

57、redatthedetectionlimit.7. QUANTITATIONLIMITSeveralapproachesfordeterminingthequantitationlimitarepossible,dependingonwhethertheprocedureisanon-instrumentalorinstrumental.Approachesotherthanthoselistedbelowmaybeacceptable.7.1. BasedonVisualEvaluationVisualevaluationmaybeusedfornon-instrumentalmethods

58、butmayalsobeusedwithinstrumentalmethods.Thequantitationlimitisgenerallydeterminedbytheanalysisofsampleswithknownconcentrationsofanalyteandbyestablishingtheminimumlevelatwhichtheanalytecanbequantifiedwithacceptableaccuracyandprecision.7.2. BasedonSignal-to-NoiseApproachThisapproachcanonlybeappliedtoanalyticalproceduresthatexhibitbaselinenoise.Determinationofthesignal-to-noiseratioisperformedbycomparingmeasuredsignalsfromsampleswithknownlowconcentrationsofanalytewiththoseofblanksamplesandbyestablishingtheminimumco