質量控制概要H

ReviewofQualityControl

質量控制概要Wewillcover(內容)Terminology術語CharacteristicsofAnalyticalMethods分析方法特性TypesofQCsamplesandhowtheyrelatetothecharacteristicsQC樣品類型和特性1DefinitionofQuality

質量的定義Tomostoftheworld(普遍上)degreeofexcellence(優(yōu)異程度)TotheISOworld(在ISO領域)degreeofagreementbetweencharacteristicsandrequirements特性與要求的吻合程度Moreimportantly(更重要)toourclients?(對客戶)2QualityControlvs.QualityAssurance(質量控制與質量保證)Qualitycontrolisaseriesofmeasurementsusedtoassessthequalityoftheanalyticaldata質量控制是一系列測量,以評價分析數據的質量Howwellisthetestfulfilling

requirements?試驗滿足要求的程度如何?3QualityControlvs.QualityAssurance(質量控制與質量保證)Qualityassuranceisamanagementplantoensuretheintegrityofdata(asystem)質量保證是一種管理計劃,以確保數據的完整性(一種體系)Providesconfidencethatrequirementswillbefulfilled為要求是否得到滿足提供信心4QualitiesofAnalyticalMethods

分析方法的質量Accuracy(準確度)Precision(精密度)Selectivity(選擇性)Sensitivity(靈敏度)Linearity(線性)Range(范圍)Robustness/Ruggedness(穩(wěn)健性/穩(wěn)度)5Accuracy(準確度)Degreeofagreementbetweenthe“true”valueandthemeasuredvalue(真值與測量值之間的一致程度)6Accuracy(準確度)Whatisthe“true”value?(什么是真值)Theoretical(理論值)Consensus(公議值)Accepted/Assigned(可接受/賦值)7Accuracy(準確度)Expressedas(表示為)theratiobetweentheassayedvalueandthe“true”value(%recovery)分析值與真值間的比(%回收率)thedifferencebetweentheassayandtheacceptedtruevalue(%Error)分析與可接受真值間的差(%誤差)8Precision(精密度)Closenessofagreementbetweenmeasurements(測量間的一致程度)Repeatability(r)–sameconditions,shorttimeinterval(samerun)–shorttermprecision重復性(r)-相同條件下\短時間間隔-短期內精密度Intermediateprecision–samelabdifferentday,analyst,instrument中間精密度-同一實驗室不同日期,分析人員,儀器Reproducibility(R)–agreementbetweenbatchesorbetweenlabs復現性?-批間或實驗室間的一致性9Precision(精密度)ExpressedasStandardDeviation,RelativeStandardDeviationorRelativePercentDifference表示為標準偏差、相對標準偏差、相對百分差10Sensitivity（（靈敏敏度度））Degreeofresponsetoachangeinanalyteconcentration––resolution被分分析析物物濃濃度度變變化化的的響響應應變變化化程程度度-分分辯辯率率Lowestconcentrationthatcanbedistinguishedfrombackgroundnoise––detectionlimit能從從背背景景噪噪音音識識別別出出的的最最低低濃濃度度-檢檢測測限限11Sensitivity（（靈敏敏度度））Limitofdetectionvs.Limitofquantification（（檢測測限限與與定定量量限限））Limitofdetection(LOD)isthelevelthatwecansaywhetherananalyteispresentornot檢測測限限是是我我們們判判斷斷被被分分析析物物是是否否存存在在的的含含量量水水平平Limitofquantitation(LOQ)isthelevelthatwecanquantifytheanalytewithaspecifiedaccuracy(20%)定量量限限是是我我們們按按規(guī)規(guī)定定準準確確度度（（20%））能能對對被被分分析析物物量量化化的的含含量量水水平平12Selectivity（選擇性）Abilitytodetecttheanalyteinacomplexmatrix檢測復雜基體體中被析物的的能力Abilitytoexcludenon-analytespeciesfromsignal通過信號排除除非被分析物物的能力Usuallyinverselyrelatedtosensitivity通常與靈敏度度成反比13Linearity（線性）Abilitytoproducearesponsethatisdirectlyproportionaltotheconcentrationoftheanalyte所產生的反應應與被分析物物濃度成正比比的能力Onlyholdstruewithinagivenrange只在給定范圍圍內是真實的的14Linearity（（線性）Expressedascorrelationcoefficient(r)orcoefficientofdetermination(r2)表示為相關系系數(r)或測定系數(r2)r2=ssxy2/ssxxssyy15Range（（范圍）Theintervalbetweenthehighestandlowestconcentrationforwhichthemethodhasshowntohavesuitablelevelsofaccuracy,precisionandlinearity.在方法具有適適宜的準確度度、精密度和和線性的條件件下，最高和和最低濃度范范圍16Robustness（（穩(wěn)健性）Abilityofmethodtobeunaffectedbysmallchangesinmethod(internal)conditions（方法不因條件件的較小變化化（內部）而而受影響的能能力）Temperature（溫度）pHCompositionofmobilephase（流動相組成））Usefulwhenmethodmovesfromdevelopmenttoproduction（（從方法開發(fā)到到使用很有用用）17Ruggedness（（穩(wěn)度）Abilityofmethodtobeunaffectedbyexternalconditions（方法不受外界界條件影響的的能力）Differentanalysts（不同的分析人人員）Differentlaboratories（不同的實驗室室）Differentreagentlots（不同批的試劑劑）Differentinstruments（不同的儀器））18Ruggedness（（穩(wěn)度）Usefulfortechnologytransfer（（對技術推廣很很有用）19QualityControlMeasures質量控制手段段Calibrationstandards（校準標準）Blanks（空白）Recoverystudies（回收率研究））Precisionstudies（精密度研究））Sensitivitystudies（靈敏度研究））DetectionLimit（（檢測限）Quantitationlimit（定量限）20Calibration(校準)Directlyaffectsaccuracy(直接影響準確確度)Preparationofstandards(標準制備)Matrix(基體)Stability(穩(wěn)定性)Signaltype:peakarea,peakheight信號類型:峰峰面積,峰高高21Calibration(校準)Calibrationcurves(校準曲線)1storder––straightline(一級-直線)Quadratic––acceptablebutrequiresmorepoints(二次方程-可可以接受,但但需要更多點點)Internalstandards(內標)Refinescalibrationresponse(增強校準響應應)Addedtosamplesandstandards(加入樣品和標標準中)Mustbehaveliketheanalyte(象被分析物一一樣表現)Cannotbeinsamples––rareelements,deuteratedcompounds(樣品中沒有-稀有元素,含重氘的化化合物)22Calibration(校準)Calibrationverification(校準驗證)Repeatedcalibrationstandard重復校準標準準Intervalmaybeevery20samples(ICPMS)oronceeveryrun(GC-FID)間隔:20個個樣品(ICPMS)每次(GC-FID)23Blanks(空白)Usedtomonitorcontamination(監(jiān)測污染)Reagentblanks(試劑空白)Instrumentblanks(儀器空白)Fieldblanks(場地空白)Tripblanks(路途空白)Procedural/methodblanks(程序/方法空空白)Matrixblanks(基體空白)Others?(其它)24RecoveryStudies（回收率研究））Usedtomonitoraccuracy（監(jiān)測準確度））Matrixspikes（基體加標）Fortifiedblanks（增加加標）Surrogates（（替代）ReferenceMaterials（參考物質）25MatrixSpikes（基體加標）Knownamountofanalyteaddedtosample在樣品中加入入已知量的被被分析物Importantwithcomplexmatrix對復雜基體很很重要Generallyaddedpriortoextractionprocess（通常在在提取取前加加入））Sometimesdifficulttoknowamounttospikeaheadoftime（有時很很難提提前知知道加加標量量）26FortifiedBlanks（（增強空空白））Analytespikeintoreagentblank在試劑劑空白白中加加入被被分析析物標標樣Carriedthroughsamplepreparationprocess在樣品品準備備過程程中加加入27Surrogate（替代））Compoundwithsimilarpropertiestotargetanalyte與被分分析物物具有有相近近特性性的化化合物物Addedtoallsamples(unknownsandQC)butnotstandards在所有有樣品品(未未知的的和QC)中加入入，但但標樣樣中不不加Usedtomonitormethodperformanceonasample(matrix)specificbasis應基于于特定定樣品品（基基體）），用用于監(jiān)監(jiān)測方方法表表現28ReferenceMaterials參考物物質Matrixmatchedmaterialswithknownconcentrationofanalytes（被分析析物已已知濃濃度的的基體體匹配配的物物質））Maybeexternalorin-house（外部或或室室內））Sources（來源））NIST(US)NRC(Canada)EuropeanUnion（（歐盟））CommercialVendors（（商業(yè)渠渠道））29ReferenceMaterials參考物物質Usedprimarilytomonitoraccuracy主要用用于監(jiān)監(jiān)測準準確度度Maybeusedforotherquality用于其其它質質量目目的measures(precision,sensitivity)測量（（精密密度、、靈敏敏度））BestoverallQC?（（最好的的全面面質量量控制制？））Expensive（費用高高）30PrecisionStudies（精密度度研究究）Duplicates（（重復））Fieldduplicates（（場地重重復））Labduplicates（（實驗室室重復復）Instrumentduplicates（儀器重重復））Inter-labsplits（（室內分分樣））Usedtoidentifyvarianceindifferentprocesses（（用于識識別不不同過過程的的變異異）31SensitivityStudies靈敏度研究究Usuallyperformedinitially,thenperiodicallythereafter通常最開始始要做，以以后定期做做Multiplereplicatesofablankorlow-levelstandard空白或低含含量標準多多次重復32SensitivityStudies靈敏度研究究DetectionLimit––noquantitation檢測限-非非定量QuantitationLimit–Accuracycriteriaadded定量限–準確度準則則33SensitivityStudies靈敏度研究究DetectionLimit––99%certaintythattheconcentrationisgreaterthanzero––thattheanalyteispresentinthesample（檢測限—99%確定定濃度大于于0-樣品品中有被分分析物）Uncertaintyishigh(+/-100%ormore)不確定度度高（+/-100%或更高））QuantitationLimit（（定量限））Lowestconcentrationthatcanbedeterminedwithagivenaccuracy(e.g.20%relativeerror)在一定準準確度下下（如20%相相對誤差差）可以以測定出出的最低低濃度34Linearity（（線性）Determinedinitiallyandthenasneeded最開始時時測定，，然后需需要時測測定DynamicLinearRangerelatestodetectorresponse動態(tài)線性性范圍與與檢測器器響應有有關Alsoconsiderpreparationlimitations也可以認認為是準準備中的的限制Solubilities（（溶解度））Extractionefficiencies（提取率））Derivitizingreactions（衍生反應應）35WhatdowerunasQC?為什么要要做質量量控制Itdependson:（取決于））Typeofinstrumentation儀器類型型StageofMethodDevelopment方法開發(fā)發(fā)階段Typeofanalysis分析類型型36WhatdowerunasQC?為什么要要做質量量控制StageofMethodDevelopment方法開發(fā)發(fā)階段Validation（確認）Verification/Qualification（驗證/判判斷）Routineanalysis（日常分析析）37WhatdowerunasQC?為什么要要做質量量控制TypeofAnalysis（分析類型型）Assay（分析）Impurities（雜質）Limits（（限制）Content（含量）Identification（識別）38QualityDataRequiredatMethodValidation（（方法確認認所需的的質量數數據）DataRequired所需數據I.D.名稱ImpurityTesting雜質檢測AssayContent分析含量Quant.量Limit限Accuracy準確度NOYESNOYESPrecision精密度NOYESNOYESSelectivity選擇性YESYESYESYESDetectionlimit檢測限NOMAYBE可能YESNOQuantitationlimit定量限NOYESNOMAYBE可能Linearity線性NOYESNOYESRange范圍NOYESNOYES39QualityDataRequiredinRoutineAnalysis日常分析析所需質質量數據據DataRequired所需數據I.D.名稱ImpurityTesting雜質檢測AssayContent分析含量Quant.量Limit限Accuracy準確度NOYESNOYESPrecision精密度NOYESNOYESSelectivity選擇性NOMAYBE1NOMAYBE1Detectionlimit檢測限NONONONOQuantitationlimit定量限NOMAYBENOMAYBELinearity線性NOYESNOYESRange范圍NONONONO1–mayberequiredwhenworkinginunknownmatrix40ReviewofQualityAssurance質量保證證概述Wewillcover（內容）DefinitionandDescriptionofQA質量保證證的定義義和描述述ToolsinaQASystem（QA體系的工工具）ProficiencyTesting（能力驗證證）CertifiedReferenceMaterials（有證標準準物質））ValidatedMethods（經過確認認的方法法）41QualityAssurance（質量保證證）QualityAssurance質量保證證Plannedactionsdesignedtoprovideconfidencethatqualityrequirementswillbefulfilled為質量要要求得到到滿足提提供信心心而設計計的有計計劃的活活動QualityAssuranceSystem質量保證證體系Asetofprocessesappliedwithinadefinedstructuretogeneratedesiredoutcomes在規(guī)定的的結構內內產生預預期結果果所采用用的一組組過程Thegoodmanagementofgoodscience良好的科科學良好好的管理理42QualitySystemComponents質量體系系組成Management管理Plan策劃Performance實施Do做Assessment評價Review評審436PillarsofQA/QC

QA/QC的六個基基礎Management管理Facilities設施Personnel人員CRM’’s有證標準準物質PT’s能力驗證證ValidatedMethods經確認的的方法44ProficiencyTesting能力驗證證Providesexternalassessmentofperformance為表現提供供外部評審審Providesabasisforcorrectiveandpreventiveaction為糾正和預預防措施提提供基礎45InformationGained搜集信息Comparisonofperformanceagainstanexternalstandard將表現與外外部標準比比較Comparisonagainstpastperformance與過去的表表現比較Comparisonagainstpeer(competitor)labs與同行（競競爭者比較較）Identificationofunsatisfactoryperformers識別出不滿滿意的操作作者46TypesofPT能力驗證類類型Specificanalyte/matrixcombination特定被分析析物/基體體結合Mercuryinfish（魚中的汞））Benzeneinair（空氣中的苯苯）Fieldofanalysis（場地分析））MetalsbyICP（ICP測金屬）PesticidesbyGC/MS（GC/MS測殺蟲劑））47Samples樣品Sub-sampledfrombulksupply從批中抽取取樣本Discretesamplesplitanddistributed謹慎分割樣樣品并分發(fā)發(fā)48InterlaboratoryComparisons實驗室間比比對Collaborativestudies協(xié)同研究Certificationstudies認證研究Round-robinstudies循環(huán)研究49SelectionofPTprogramsPT方案的選擇擇Availabilityofrelevantprograms是否有相關關方案Organizationofrelevantprograms相關方案的的組織Anyprogramisusuallybetterthannothing只有要方案案，總比沒沒有好50AssessmentofPTPrograms

PT方案的評價價Beforecommittinglong-termconsider在實施前應應考慮Statisticsusedtointerpretdata解釋結果的的統(tǒng)計技術術How““true”valueisdetermined真值如何確確定Theoretical理論值Refereelab參考實驗室室Consensus公議值51ScoringofParticipants參加者的評評價Z–score（Z值）Deviationfrom“true””valuedividedbysigma測得值與真真值之差除除以σSigmamaybeanaccepteddeviationorstatisticallydeterminedineachroundσ可能能是是可可接接受受的的偏偏差差或或每每輪輪測測試試的的統(tǒng)統(tǒng)計計結結果果52ScoringZ-值GenerallyaZ-score（（Z-值））<2isconsideredsatisfactory（（滿意意））>2,<3isconsideredquestionable（（可疑疑））>3isconsideredunsatisfactory（（離群群））scoresmustbewithin2––sigmaZ-值必必須須在在2-σ之間間53LaboratoryInterpretation實驗驗室室的的解解釋釋Viewresultsincontext（（從整整體體上上看看結結果果））Dotheyagreewithin-houseQCdata是否否與與室室內內質質量量控控制制數數據據一一致致Trendanalysis(considerhowsigmaisdetermined)趨勢勢分分析析（（考考慮慮σ是如如何何確確定定的的））Performanceofotherparticipants其它它參參加加者者的的表表現現54LaboratoryInterpretation實驗驗室室的的解解釋釋Comparemethodologyandre-calculateifpossible比較方法，如如果可能重新新計算Compareuncertaintyagainstin-houseestimates將不確定度與與室內評估比比較55CorrectiveActions糾正措施Determinewhentotakeaction確定何時采取取措施After1unsatisfactoryscore?一個不滿意結結果Aftermany(3)inoneround?一輪中多個（（如三個）不不滿意結果After2consecutiveunsatisfactoryscores?連續(xù)二個不滿滿意結果56CorrectiveActions糾正措施Alwaysinvestigate總要調查Include包括QCdata質量控制數據據Calculations,dilutions,transcriptions計算、稀釋，，抄寫Trainingstatusofanalyst分析人員培訓訓狀況Performancerecordsofequipment設備運行記錄錄Recordsofcalibrants,reagentsetc.校準品、試劑劑的記錄等57CorrectiveActions糾正措施Formulateaction公布措施Executeaction實施措施Checkifactionwassuccessful檢查措施是否否有效58GeneralConsiderations幾點考考慮MoreemphasisisbeingplacedonPTprogramsbyassessors,regulatorsandclients評審員員、管管理部部門和和客戶戶更多多強調調PTUsealltheinformationavailable利用所所有可可得到到的信信息HandlePT’slikeroutinesamples(asmuchaspossible)象常規(guī)規(guī)樣品品一樣樣處理理PT樣品（（盡可可能））59ThirdPartyAssessment第三方方評審審AccreditationBodies認可機機構AssessperformanceagainstlaboratoryscoperatherthanPTprogramcriteria在一定定范圍圍內評評審實實驗室室的表表現，，而不不是PT方案準準則Consider““fitforpurpose”考慮適適宜性性60ThirdPartyAssessment第三方方評審審Regulators政府管管理部部門MaybeinvolvedindevelopmentofPTprograms可能參參與PT方案的的開發(fā)發(fā)Mayrequireassistancefromprogramcoordinatortoassessresults可能需需要方方案協(xié)協(xié)調人人來幫幫助評評審結結果61ThirdPartyAssessment第三方方評審審Customers客戶WhenusingPTresultsasaperformancestandardensuretargetisrealistic當使用用PT結果作作為能能力標標準時時，確確保目目標是是現實實的Mustinvestigateprogram;notjustresults必須調調查方方案，，而不不僅是是結果果62ReferenceMaterials參考物物質5types（5種類型型）Puresubstance（（純物質質）Standardsolutionsandgasmixtures（標準溶溶液和和氣體體混合合物））MatrixRM’s（基體參參考物物質））Physicalproperties（物理特特性））Referenceobjects(artifacts)（參考目目標））（參參考品品）63ReferenceMaterials參考物物質Maybeusedfor可用于于InternalQC內部質質量控控制Methodvalidation方法確確認Calibration校準Estimatinguncertainty評估不不確定定度Training培訓64Classification分類CertifiedReferenceMaterials有證參參考物物質Directlytraceable直接溯溯源Eachpropertyhasanuncertaintyassociatedwithit每一特特性有有相應應不確確定度度Referencematerial參考物物質Propertiesarehomogenousandthoroughlycharacterizedtobeusedforcalibrationormethodassessment特性是是均勻勻的，，并完完整定定值，，以用用于校校準或或方法法評價價65Availability可獲得得性Generallypoorthereforeexpensive(不容易易獲得得,費費用高高)Governmentagencies政府機機構NIST,NRC,EU-BCRTradea