质量控制概要H

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1DefinitionofQuality

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)2QualityControlvs.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Howwellisthetestfulfilling

requirements?试验满足要求的程度如何?3QualityControlvs.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4QualitiesofAnalyticalMethods

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)5Accuracy(准确度)Degreeofagreementbetweenthe“true”valueandthemeasuredvalue(真值与测量值之间的一致程度)6Accuracy(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)7Accuracy(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)8Precision(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Intermediateprecision–samelabdifferentday,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9Precision(精密度)ExpressedasStandardDeviation,RelativeStandardDeviationorRelativePercentDifference表示为标准偏差、相对标准偏差、相对百分差10Sensitivity（（灵敏敏度度））Degreeofresponsetoachangeinanalyteconcentration––resolution被分分析析物物浓浓度度变变化化的的响响应应变变化化程程度度-分分辩辩率率Lowestconcentrationthatcanbedistinguishedfrombackgroundnoise––detectionlimit能从从背背景景噪噪音音识识别别出出的的最最低低浓浓度度-检检测测限限11Sensitivity（（灵敏敏度度））Limitofdetectionvs.Limitofquantification（（检测测限限与与定定量量限限））Limitofdetection(LOD)isthelevelthatwecansaywhetherananalyteispresentornot检测测限限是是我我们们判判断断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们们按按规规定定准准确确度度（（20%））能能对对被被分分析析物物量量化化的的含含量量水水平平12Selectivity（选择性）Abilitytodetecttheanalyteinacomplexmatrix检测复杂基体体中被析物的的能力Abilitytoexcludenon-analytespeciesfromsignal通过信号排除除非被分析物物的能力Usuallyinverselyrelatedtosensitivity通常与灵敏度度成反比13Linearity（线性）Abilitytoproducearesponsethatisdirectlyproportionaltotheconcentrationoftheanalyte所产生的反应应与被分析物物浓度成正比比的能力Onlyholdstruewithinagivenrange只在给定范围围内是真实的的14Linearity（（线性）Expressedascorrelationcoefficient(r)orcoefficientofdetermination(r2)表示为相关系系数(r)或测定系数(r2)r2=ssxy2/ssxxssyy15Range（（范围）Theintervalbetweenthehighestandlowestconcentrationforwhichthemethodhasshowntohavesuitablelevelsofaccuracy,precisionandlinearity.在方法具有适适宜的准确度度、精密度和和线性的条件件下，最高和和最低浓度范范围16Robustness（（稳健性）Abilityofmethodtobeunaffectedbysmallchangesinmethod(internal)conditions（方法不因条件件的较小变化化（内部）而而受影响的能能力）Temperature（温度）pHCompositionofmobilephase（流动相组成））Usefulwhenmethodmovesfromdevelopmenttoproduction（（从方法开发到到使用很有用用）17Ruggedness（（稳度）Abilityofmethodtobeunaffectedbyexternalconditions（方法不受外界界条件影响的的能力）Differentanalysts（不同的分析人人员）Differentlaboratories（不同的实验室室）Differentreagentlots（不同批的试剂剂）Differentinstruments（不同的仪器））18Ruggedness（（稳度）Usefulfortechnologytransfer（（对技术推广很很有用）19QualityControlMeasures质量控制手段段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）20Calibration(校准)Directlyaffectsaccuracy(直接影响准确确度)Preparationofstandards(标准制备)Matrix(基体)Stability(稳定性)Signaltype:peakarea,peakheight信号类型:峰峰面积,峰高高21Calibration(校准)Calibrationcurves(校准曲线)1storder––straightline(一级-直线)Quadratic––acceptablebutrequiresmorepoints(二次方程-可可以接受,但但需要更多点点)Internalstandards(内标)Refinescalibrationresponse(增强校准响应应)Addedtosamplesandstandards(加入样品和标标准中)Mustbehaveliketheanalyte(象被分析物一一样表现)Cannotbeinsamples––rareelements,deuteratedcompounds(样品中没有-稀有元素,含重氘的化化合物)22Calibration(校准)Calibrationverification(校准验证)Repeatedcalibrationstandard重复校准标准准Intervalmaybeevery20samples(ICPMS)oronceeveryrun(GC-FID)间隔:20个个样品(ICPMS)每次(GC-FID)23Blanks(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/方法空空白)Matrixblanks(基体空白)Others?(其它)24RecoveryStudies（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）25MatrixSpikes（基体加标）Knownamountofanalyteaddedtosample在样品中加入入已知量的被被分析物Importantwithcomplexmatrix对复杂基体很很重要Generallyaddedpriortoextractionprocess（通常在在提取取前加加入））Sometimesdifficulttoknowamounttospikeaheadoftime（有时很很难提提前知知道加加标量量）26FortifiedBlanks（（增强空空白））Analytespikeintoreagentblank在试剂剂空白白中加加入被被分析析物标标样Carriedthroughsamplepreparationprocess在样品品准备备过程程中加加入27Surrogate（替代））Compoundwithsimilarpropertiestotargetanalyte与被分分析物物具有有相近近特性性的化化合物物Addedtoallsamples(unknownsandQC)butnotstandards在所有有样品品(未未知的的和QC)中加入入，但但标样样中不不加Usedtomonitormethodperformanceonasample(matrix)specificbasis应基于于特定定样品品（基基体）），用用于监监测方方法表表现28ReferenceMaterials参考物物质Matrixmatchedmaterialswithknownconcentrationofanalytes（被分析析物已已知浓浓度的的基体体匹配配的物物质））Maybeexternalorin-house（外部或或室室内））Sources（来源））NIST(US)NRC(Canada)EuropeanUnion（（欧盟））CommercialVendors（（商业渠渠道））29ReferenceMaterials参考物物质Usedprimarilytomonitoraccuracy主要用用于监监测准准确度度Maybeusedforotherquality用于其其它质质量目目的measures(precision,sensitivity)测量（（精密密度、、灵敏敏度））BestoverallQC?（（最好的的全面面质量量控制制？））Expensive（费用高高）30PrecisionStudies（精密度度研究究）Duplicates（（重复））Fieldduplicates（（场地重重复））Labduplicates（（实验室室重复复）Instrumentduplicates（仪器重重复））Inter-labsplits（（室内分分样））Usedtoidentifyvarianceindifferentprocesses（（用于识识别不不同过过程的的变异异）31SensitivityStudies灵敏度研究究Usuallyperformedinitially,thenperiodicallythereafter通常最开始始要做，以以后定期做做Multiplereplicatesofablankorlow-levelstandard空白或低含含量标准多多次重复32SensitivityStudies灵敏度研究究DetectionLimit––noquantitation检测限-非非定量QuantitationLimit–Accuracycriteriaadded定量限–准确度准则则33SensitivityStudies灵敏度研究究DetectionLimit––99%certaintythattheconcentrationisgreaterthanzero––thattheanalyteispresentinthesample（检测限—99%确定定浓度大于于0-样品品中有被分分析物）Uncertaintyishigh(+/-100%ormore)不确定度度高（+/-100%或更高））QuantitationLimit（（定量限））Lowestconcentrationthatcanbedeterminedwithagivenaccuracy(e.g.20%relativeerror)在一定准准确度下下（如20%相相对误差差）可以以测定出出的最低低浓度34Linearity（（线性）Determinedinitiallyandthenasneeded最开始时时测定，，然后需需要时测测定DynamicLinearRangerelatestodetectorresponse动态线性性范围与与检测器器响应有有关Alsoconsiderpreparationlimitations也可以认认为是准准备中的的限制Solubilities（（溶解度））Extractionefficiencies（提取率））Derivitizingreactions（衍生反应应）35WhatdowerunasQC?为什么要要做质量量控制Itdependson:（取决于））Typeofinstrumentation仪器类型型StageofMethodDevelopment方法开发发阶段Typeofanalysis分析类型型36WhatdowerunasQC?为什么要要做质量量控制StageofMethodDevelopment方法开发发阶段Validation（确认）Verification/Qualification（验证/判判断）Routineanalysis（日常分析析）37WhatdowerunasQC?为什么要要做质量量控制TypeofAnalysis（分析类型型）Assay（分析）Impurities（杂质）Limits（（限制）Content（含量）Identification（识别）38QualityDataRequiredatMethodValidation（（方法确认认所需的的质量数数据）DataRequired所需数据I.D.名称ImpurityTesting杂质检测AssayContent分析含量Quant.量Limit限Accuracy准确度NOYESNOYESPrecision精密度NOYESNOYESSelectivity选择性YESYESYESYESDetectionlimit检测限NOMAYBE可能YESNOQuantitationlimit定量限NOYESNOMAYBE可能Linearity线性NOYESNOYESRange范围NOYESNOYES39QualityDataRequiredinRoutineAnalysis日常分析析所需质质量数据据DataRequired所需数据I.D.名称ImpurityTesting杂质检测AssayContent分析含量Quant.量Limit限Accuracy准确度NOYESNOYESPrecision精密度NOYESNOYESSelectivity选择性NOMAYBE1NOMAYBE1Detectionlimit检测限NONONONOQuantitationlimit定量限NOMAYBENOMAYBELinearity线性NOYESNOYESRange范围NONONONO1–mayberequiredwhenworkinginunknownmatrix40ReviewofQualityAssurance质量保证证概述Wewillcover（内容）DefinitionandDescriptionofQA质量保证证的定义义和描述述ToolsinaQASystem（QA体系的工工具）ProficiencyTesting（能力验证证）CertifiedReferenceMaterials（有证标准准物质））ValidatedMethods（经过确认认的方法法）41QualityAssurance（质量保证证）QualityAssurance质量保证证Plannedactionsdesignedtoprovideconfidencethatqualityrequirementswillbefulfilled为质量要要求得到到满足提提供信心心而设计计的有计计划的活活动QualityAssuranceSystem质量保证证体系Asetofprocessesappliedwithinadefinedstructuretogeneratedesiredoutcomes在规定的的结构内内产生预预期结果果所采用用的一组组过程Thegoodmanagementofgoodscience良好的科科学良好好的管理理42QualitySystemComponents质量体系系组成Management管理Plan策划Performance实施Do做Assessment评价Review评审436PillarsofQA/QC

QA/QC的六个基基础Management管理Facilities设施Personnel人员CRM’’s有证标准准物质PT’s能力验证证ValidatedMethods经确认的的方法44ProficiencyTesting能力验证证Providesexternalassessmentofperformance为表现提供供外部评审审Providesabasisforcorrectiveandpreventiveaction为纠正和预预防措施提提供基础45InformationGained搜集信息Comparisonofperformanceagainstanexternalstandard将表现与外外部标准比比较Comparisonagainstpastperformance与过去的表表现比较Comparisonagainstpeer(competitor)labs与同行（竞竞争者比较较）Identificationofunsatisfactoryperformers识别出不满满意的操作作者46TypesofPT能力验证类类型Specificanalyte/matrixcombination特定被分析析物/基体体结合Mercuryinfish（鱼中的汞））Benzeneinair（空气中的苯苯）Fieldofanalysis（场地分析））MetalsbyICP（ICP测金属）PesticidesbyGC/MS（GC/MS测杀虫剂））47Samples样品Sub-sampledfrombulksupply从批中抽取取样本Discretesamplesplitanddistributed谨慎分割样样品并分发发48InterlaboratoryComparisons实验室间比比对Collaborativestudies协同研究Certificationstudies认证研究Round-robinstudies循环研究49SelectionofPTprogramsPT方案的选择择Availabilityofrelevantprograms是否有相关关方案Organizationofrelevantprograms相关方案的的组织Anyprogramisusuallybetterthannothing只有要方案案，总比没没有好50AssessmentofPTPrograms

PT方案的评价价Beforecommittinglong-termconsider在实施前应应考虑Statisticsusedtointerpretdata解释结果的的统计技术术How““true”valueisdetermined真值如何确确定Theoretical理论值Refereelab参考实验室室Consensus公议值51ScoringofParticipants参加者的评评价Z–score（Z值）Deviationfrom“true””valuedividedbysigma测得值与真真值之差除除以σSigmamaybeanaccepteddeviationorstatisticallydeterminedineachroundσ可能能是是可可接接受受的的偏偏差差或或每每轮轮测测试试的的统统计计结结果果52ScoringZ-值GenerallyaZ-score（（Z-值））<2isconsideredsatisfactory（（满意意））>2,<3isconsideredquestionable（（可疑疑））>3isconsideredunsatisfactory（（离群群））scoresmustbewithin2––sigmaZ-值必必须须在在2-σ之间间53LaboratoryInterpretation实验验室室的的解解释释Viewresultsincontext（（从整整体体上上看看结结果果））Dotheyagreewithin-houseQCdata是否否与与室室内内质质量量控控制制数数据据一一致致Trendanalysis(considerhowsigmaisdetermined)趋势势分分析析（（考考虑虑σ是如如何何确确定定的的））Performanceofotherparticipants其它它参参加加者者的的表表现现54LaboratoryInterpretation实验验室室的的解解释释Comparemethodologyandre-calculateifpossible比较方法，如如果可能重新新计算Compareuncertaintyagainstin-houseestimates将不确定度与与室内评估比比较55CorrectiveActions纠正措施Determinewhentotakeaction确定何时采取取措施After1unsatisfactoryscore?一个不满意结结果Aftermany(3)inoneround?一轮中多个（（如三个）不不满意结果After2consecutiveunsatisfactoryscores?连续二个不满满意结果56CorrectiveActions纠正措施Alwaysinvestigate总要调查Include包括QCdata质量控制数据据Calculations,dilutions,transcriptions计算、稀释，，抄写Trainingstatusofanalyst分析人员培训训状况Performancerecordsofequipment设备运行记录录Recordsofcalibrants,reagentsetc.校准品、试剂剂的记录等57CorrectiveActions纠正措施Formulateaction公布措施Executeaction实施措施Checkifactionwassuccessful检查措施是否否有效58GeneralConsiderations几点考考虑MoreemphasisisbeingplacedonPTprogramsbyassessors,regulatorsandclients评审员员、管管理部部门和和客户户更多多强调调PTUsealltheinformationavailable利用所所有可可得到到的信信息HandlePT’slikeroutinesamples(asmuchaspossible)象常规规样品品一样样处理理PT样品（（尽可可能））59ThirdPartyAssessment第三方方评审审AccreditationBodies认可机机构AssessperformanceagainstlaboratoryscoperatherthanPTprogramcriteria在一定定范围围内评评审实实验室室的表表现，，而不不是PT方案准准则Consider““fitforpurpose”考虑适适宜性性60ThirdPartyAssessment第三方方评审审Regulators政府管管理部部门MaybeinvolvedindevelopmentofPTprograms可能参参与PT方案的的开发发Mayrequireassistancefromprogramcoordinatortoassessresults可能需需要方方案协协调人人来帮帮助评评审结结果61ThirdPartyAssessment第三方方评审审Customers客户WhenusingPTresultsasaperformancestandardensuretargetisrealistic当使用用PT结果作作为能能力标标准时时，确确保目目标是是现实实的Mustinvestigateprogram;notjustresults必须调调查方方案，，而不不仅是是结果果62ReferenceMaterials参考物物质5types（5种类型型）Puresubstance（（纯物质质）Standardsolutionsandgasmixtures（标准溶溶液和和气体体混合合物））MatrixRM’s（基体参参考物物质））Physicalproperties（物理特特性））Referenceobjects(artifacts)（参考目目标））（参参考品品）63ReferenceMaterials参考物物质Maybeusedfor可用于于InternalQC内部质质量控控制Methodvalidation方法确确认Calibration校准Estimatinguncertainty评估不不确定定度Training培训64Classification分类CertifiedReferenceMaterials有证参参考物物质Directlytraceable直接溯溯源Eachpropertyhasanuncertaintyassociatedwithit每一特特性有有相应应不确确定度度Referencematerial参考物物质Propertiesarehomogenousandthoroughlycharacterizedtobeusedforcalibrationormethodassessment特性是是均匀匀的，，并完完整定定值，，以用用于校校准或或方法法评价价65Availability可获得得性Generallypoorthereforeexpensive(不容易易获得得,费费用高高)Governmentagencies政府机机构NIST,NRC,EU-BCRTradea