质量控制概要-PHP.ppt

ReviewofQualityControl质量控制概要,Wewillcover(内容)Terminology术语CharacteristicsofAnalyticalMethods分析方法特性TypesofQCsamplesandhowtheyrelatetothecharacteristicsQC样品类型和特性,DefinitionofQuality质量的定义,Tomostoftheworld(普遍上)degreeofexcellence(优异程度)TotheISOworld(在ISO领域)degreeofagreementbetweencharacteristicsandrequirements特性与要求的吻合程度Moreimportantly(更重要)toourclients?(对客户),QualityControlvs.QualityAssurance(质量控制与质量保证),Qualitycontrolisaseriesofmeasurementsusedtoassessthequalityoftheanalyticaldata质量控制是一系列测量,以评价分析数据的质量Howwellisthetestfulfillingrequirements?试验满足要求的程度如何?,QualityControlvs.QualityAssurance(质量控制与质量保证),Qualityassuranceisamanagementplantoensuretheintegrityofdata(asystem)质量保证是一种管理计划,以确保数据的完整性(一种体系)Providesconfidencethatrequirementswillbefulfilled为要求是否得到满足提供信心,QualitiesofAnalyticalMethods分析方法的质量,Accuracy(准确度)Precision(精密度)Selectivity(选择性)Sensitivity(灵敏度)Linearity(线性)Range(范围)Robustness/Ruggedness(稳健性/稳度),Accuracy(准确度),Degreeofagreementbetweenthe“true”valueandthemeasuredvalue(真值与测量值之间的一致程度),Accuracy(准确度),Whatisthe“true”value?(什么是真值)Theoretical(理论值)Consensus(公议值)Accepted/Assigned(可接受/赋值),Accuracy(准确度),Expressedas(表示为)theratiobetweentheassayedvalueandthe“true”value(%recovery)分析值与真值间的比(%回收率)thedifferencebetweentheassayandtheacceptedtruevalue(%Error)分析与可接受真值间的差(%误差),Precision(精密度),Closenessofagreementbetweenmeasurements(测量间的一致程度)Repeatability(r)sameconditions,shorttimeinterval(samerun)shorttermprecision重复性(r)-相同条件下短时间间隔-短期内精密度Intermediateprecisionsamelabdifferentday,analyst,instrument中间精密度-同一实验室不同日期,分析人员,仪器Reproducibility(R)agreementbetweenbatchesorbetweenlabs复现性-批间或实验室间的一致性,Precision(精密度),ExpressedasStandardDeviation,RelativeStandardDeviationorRelativePercentDifference表示为标准偏差、相对标准偏差、相对百分差,Sensitivity（灵敏度）,Degreeofresponsetoachangeinanalyteconcentrationresolution被分析物浓度变化的响应变化程度-分辩率Lowestconcentrationthatcanbedistinguishedfrombackgroundnoisedetectionlimit能从背景噪音识别出的最低浓度-检测限,Sensitivity（灵敏度）,Limitofdetectionvs.Limitofquantification（检测限与定量限）Limitofdetection(LOD)isthelevelthatwecansaywhetherananalyteispresentornot检测限是我们判断被分析物是否存在的含量水平Limitofquantitation(LOQ)isthelevelthatwecanquantifytheanalytewithaspecifiedaccuracy(20%)定量限是我们按规定准确度（20%）能对被分析物量化的含量水平,Selectivity（选择性）,Abilitytodetecttheanalyteinacomplexmatrix检测复杂基体中被析物的能力Abilitytoexcludenon-analytespeciesfromsignal通过信号排除非被分析物的能力Usuallyinverselyrelatedtosensitivity通常与灵敏度成反比,Linearity（线性）,Abilitytoproducearesponsethatisdirectlyproportionaltotheconcentrationoftheanalyte所产生的反应与被分析物浓度成正比的能力Onlyholdstruewithinagivenrange只在给定范围内是真实的,Linearity（线性）,Expressedascorrelationcoefficient(r)orcoefficientofdetermination(r2)表示为相关系数(r)或测定系数(r2),r2=ssxy2/ssxxssyy,Range（范围）,Theintervalbetweenthehighestandlowestconcentrationforwhichthemethodhasshowntohavesuitablelevelsofaccuracy,precisionandlinearity.在方法具有适宜的准确度、精密度和线性的条件下，最高和最低浓度范围,Robustness（稳健性）,Abilityofmethodtobeunaffectedbysmallchangesinmethod(internal)conditions（方法不因条件的较小变化（内部）而受影响的能力）Temperature（温度）pHCompositionofmobilephase（流动相组成）Usefulwhenmethodmovesfromdevelopmenttoproduction（从方法开发到使用很有用）,Ruggedness（稳度）,Abilityofmethodtobeunaffectedbyexternalconditions（方法不受外界条件影响的能力）Differentanalysts（不同的分析人员）Differentlaboratories（不同的实验室）Differentreagentlots（不同批的试剂）Differentinstruments（不同的仪器）,Ruggedness（稳度）,Usefulfortechnologytransfer（对技术推广很有用）,QualityControlMeasures质量控制手段,Calibrationstandards（校准标准）Blanks（空白）Recoverystudies（回收率研究）Precisionstudies（精密度研究）Sensitivitystudies（灵敏度研究）DetectionLimit（检测限）Quantitationlimit（定量限）,Calibration(校准),Directlyaffectsaccuracy(直接影响准确度)Preparationofstandards(标准制备)Matrix(基体)Stability(稳定性)Signaltype:peakarea,peakheight信号类型:峰面积,峰高,Calibration(校准),Calibrationcurves(校准曲线)1storderstraightline(一级-直线)Quadraticacceptablebutrequiresmorepoints(二次方程-可以接受,但需要更多点)Internalstandards(内标)Refinescalibrationresponse(增强校准响应)Addedtosamplesandstandards(加入样品和标准中)Mustbehaveliketheanalyte(象被分析物一样表现)Cannotbeinsamplesrareelements,deuteratedcompounds(样品中没有-稀有元素,含重氘的化合物),Calibration(校准),Calibrationverification(校准验证)Repeatedcalibrationstandard重复校准标准Intervalmaybeevery20samples(ICPMS)oronceeveryrun(GC-FID)间隔:20个样品(ICPMS)每次(GC-FID),Blanks(空白),Usedtomonitorcontamination(监测污染)Reagentblanks(试剂空白)Instrumentblanks(仪器空白)Fieldblanks(场地空白)Tripblanks(路途空白)Procedural/methodblanks(程序/方法空白)Matrixblanks(基体空白)Others?(其它),RecoveryStudies（回收率研究）,Usedtomonitoraccuracy（监测准确度）Matrixspikes（基体加标）Fortifiedblanks（增加加标）Surrogates（替代）ReferenceMaterials（参考物质）,MatrixSpikes（基体加标）,Knownamountofanalyteaddedtosample在样品中加入已知量的被分析物Importantwithcomplexmatrix对复杂基体很重要Generallyaddedpriortoextractionprocess（通常在提取前加入）Sometimesdifficulttoknowamounttospikeaheadoftime（有时很难提前知道加标量）,FortifiedBlanks（增强空白）,Analytespikeintoreagentblank在试剂空白中加入被分析物标样Carriedthroughsamplepreparationprocess在样品准备过程中加入,Surrogate（替代）,Compoundwithsimilarpropertiestotargetanalyte与被分析物具有相近特性的化合物Addedtoallsamples(unknownsandQC)butnotstandards在所有样品(未知的和QC)中加入，但标样中不加Usedtomonitormethodperformanceonasample(matrix)specificbasis应基于特定样品（基体），用于监测方法表现,ReferenceMaterials参考物质,Matrixmatchedmaterialswithknownconcentrationofanalytes（被分析物已知浓度的基体匹配的物质）Maybeexternalorin-house（外部或室内）Sources（来源）NIST(US)NRC(Canada)EuropeanUnion（欧盟）CommercialVendors（商业渠道）,ReferenceMaterials参考物质,Usedprimarilytomonitoraccuracy主要用于监测准确度Maybeusedforotherquality用于其它质量目的measures(precision,sensitivity)测量（精密度、灵敏度）BestoverallQC?（最好的全面质量控制？）Expensive（费用高）,PrecisionStudies（精密度研究）,Duplicates（重复）Fieldduplicates（场地重复）Labduplicates（实验室重复）Instrumentduplicates（仪器重复）Inter-labsplits（室内分样）Usedtoidentifyvarianceindifferentprocesses（用于识别不同过程的变异）,SensitivityStudies灵敏度研究,Usuallyperformedinitially,thenperiodicallythereafter通常最开始要做，以后定期做Multiplereplicatesofablankorlow-levelstandard空白或低含量标准多次重复,SensitivityStudies灵敏度研究,DetectionLimitnoquantitation检测限-非定量QuantitationLimitAccuracycriteriaadded定量限准确度准则,SensitivityStudies灵敏度研究,DetectionLimit99%certaintythattheconcentrationisgreaterthanzerothattheanalyteispresentinthesample（检测限99%确定浓度大于0-样品中有被分析物）Uncertaintyishigh(+/-100%ormore)不确定度高（+/-100%或更高）QuantitationLimit（定量限）Lowestconcentrationthatcanbedeterminedwithagivenaccuracy(e.g.20%relativeerror)在一定准确度下（如20%相对误差）可以测定出的最低浓度,Linearity（线性）,Determinedinitiallyandthenasneeded最开始时测定，然后需要时测定DynamicLinearRangerelatestodetectorresponse动态线性范围与检测器响应有关Alsoconsiderpreparationlimitations也可以认为是准备中的限制Solubilities（溶解度）Extractionefficiencies（提取率）Derivitizingreactions（衍生反应）,WhatdowerunasQC?为什么要做质量控制,Itdependson:（取决于）Typeofinstrumentation仪器类型StageofMethodDevelopment方法开发阶段Typeofanalysis分析类型,WhatdowerunasQC?为什么要做质量控制,StageofMethodDevelopment方法开发阶段Validation（确认）Verification/Qualification（验证/判断）Routineanalysis（日常分析）,WhatdowerunasQC?为什么要做质量控制,TypeofAnalysis（分析类型）Assay（分析）Impurities（杂质）Limits（限制）Content（含量）Identification（识别）,QualityDataRequiredatMethodValidation（方法确认所需的质量数据）,QualityDataRequiredinRoutineAnalysis日常分析所需质量数据,1mayberequiredwhenworkinginunknownmatrix,ReviewofQualityAssurance质量保证概述,Wewillcover（内容）DefinitionandDescriptionofQA质量保证的定义和描述ToolsinaQASystem（QA体系的工具）ProficiencyTesting（能力验证）CertifiedReferenceMaterials（有证标准物质）ValidatedMethods（经过确认的方法）,QualityAssurance（质量保证）,QualityAssurance质量保证Plannedactionsdesignedtoprovideconfidencethatqualityrequirementswillbefulfilled为质量要求得到满足提供信心而设计的有计划的活动QualityAssuranceSystem质量保证体系Asetofprocessesappliedwithinadefinedstructuretogeneratedesiredoutcomes在规定的结构内产生预期结果所采用的一组过程,Thegoodmanagementofgoodscience良好的科学良好的管理,QualitySystemComponents质量体系组成,Management管理Plan策划Performance实施Do做Assessment评价Review评审,6PillarsofQA/QCQA/QC的六个基础,Management管理Facilities设施Personnel人员CRMs有证标准物质PTs能力验证ValidatedMethods经确认的方法,ProficiencyTesting能力验证,Providesexternalassessmentofperformance为表现提供外部评审Providesabasisforcorrectiveandpreventiveaction为纠正和预防措施提供基础,InformationGained搜集信息,Comparisonofperformanceagainstanexternalstandard将表现与外部标准比较Comparisonagainstpastperformance与过去的表现比较Comparisonagainstpeer(competitor)labs与同行（竞争者比较）Identificationofunsatisfactoryperformers识别出不满意的操作者,TypesofPT能力验证类型,Specificanalyte/matrixcombination特定被分析物/基体结合Mercuryinfish（鱼中的汞）Benzeneinair（空气中的苯）Fieldofanalysis（场地分析）MetalsbyICP（ICP测金属）PesticidesbyGC/MS（GC/MS测杀虫剂）,Samples样品,Sub-sampledfrombulksupply从批中抽取样本Discretesamplesplitanddistributed谨慎分割样品并分发,InterlaboratoryComparisons实验室间比对,Collaborativestudies协同研究Certificationstudies认证研究Round-robinstudies循环研究,SelectionofPTprogramsPT方案的选择,Availabilityofrelevantprograms是否有相关方案Organizationofrelevantprograms相关方案的组织Anyprogramisusuallybetterthannothing只有要方案，总比没有好,AssessmentofPTProgramsPT方案的评价,Beforecommittinglong-termconsider在实施前应考虑Statisticsusedtointerpretdata解释结果的统计技术How“true”valueisdetermined真值如何确定Theoretical理论值Refereelab参考实验室Consensus公议值,ScoringofParticipants参加者的评价,Zscore（Z值）Deviationfrom“true”valuedividedbysigma测得值与真值之差除以Sigmamaybeanaccepteddeviationorstatisticallydeterminedineachround可能是可接受的偏差或每轮测试的统计结果,ScoringZ-值,GenerallyaZ-score（Z-值）2,3isconsideredunsatisfactory（离群）scoresmustbewithin2sigmaZ-值必须在2-之间,LaboratoryInterpretation实验室的解释,Viewresultsincontext（从整体上看结果）Dotheyagreewithin-houseQCdata是否与室内质量控制数据一致Trendanalysis(considerhowsigmaisdetermined)趋势分析（考虑是如何确定的）Performanceofotherparticipants其它参加者的表现,LaboratoryInterpretation实验室的解释,Comparemethodologyandre-calculateifpossible比较方法，如果可能重新计算Compareuncertaintyagainstin-houseestimates将不确定度与室内评估比较,CorrectiveActions纠正措施,Determinewhentotakeaction确定何时采取措施After1unsatisfactoryscore?一个不满意结果Aftermany(3)inoneround?一轮中多个（如三个）不满意结果After2consecutiveunsatisfactoryscores?连续二个不满意结果,CorrectiveActions纠正措施,Alwaysinvestigate总要调查Include包括QCdata质量控制数据Calculations,dilutions,transcriptions计算、稀释，抄写Trainingstatusofanalyst分析人员培训状况Performancerecordsofequipment设备运行记录Recordsofcalibrants,reagentsetc.校准品、试剂的记录等,CorrectiveActions纠正措施,Formulateaction公布措施Executeaction实施措施Checkifactionwassuccessful检查措施是否有效,GeneralConsiderations几点考虑,MoreemphasisisbeingplacedonPTprogramsbyassessors,regulatorsandclients评审员、管理部门和客户更多强调PTUsealltheinformationavailable利用所有可得到的信息HandlePTslikeroutinesamples(asmuchaspossible)象常规样品一样处理PT样品（尽可能）,ThirdPartyAssessment第三方评审,AccreditationBodies认可机构AssessperformanceagainstlaboratoryscoperatherthanPTprogramcriteria在一定范围内评审实验室的表现，而不是PT方案准则Consider“fitforpurpose”考虑适宜性,ThirdPartyAssessment第三方评审,Regulators政府管理部门MaybeinvolvedindevelopmentofPTprograms可能参与PT方案的开发Mayrequireassistancefromprogramcoordinatortoassessresults可能需要方案协调人来帮助评审结果,ThirdPartyAssessment第三方评审,Customers客户WhenusingPTresultsasaperformancestandardensuretargetisrealistic当使用PT结果作为能力标准时，确保目标是现实的Mustinvestigateprogram;notjustresults必须调查方案，而不仅是结果,ReferenceMaterials参考物质,5types（5种类型）Puresubstance（纯物质）Standardsolutionsandgasmixtures（标准溶液和气体混合物）MatrixRMs（基体参考物质）Physicalproperties（物理特性）Referenceobjects(artifacts)（参考目标）（参考品）,ReferenceMaterials参考物质,Maybeusedfor可用于InternalQC内部质量控制Methodvalidation方法确认Calibration校准Estimatinguncertainty评估不确定度Training培训,Classification分类,CertifiedReferenceMaterials有证参考物质Directlytraceable直接溯源Eachpropertyhasanuncertaintyassociatedwithit每一特性有相应不确定度Referencematerial参考物质Propertiesarehomogenousandthoroughlycharacterizedtobeusedforcalibrationormethodassessment特性是均匀的，并完整定值，以用于校准或方法评价,Availability可获得性,Generallypoor