質(zhì)量控制概要-PHPppt課件

1、 Review of Quality Control質(zhì)量控制概要We will cover(內(nèi)容)Terminology術(shù)語Characteristics of Analytical Methods分析方法特性Types of QC samples and how they relate to the characteristicsQC樣品類型和特性.Definition of Quality質(zhì)量的定義To most of the world (普遍上) degree of excellence(優(yōu)良程度)To the ISO world (在ISO領(lǐng)域) degree of agreemen

2、t between characteristics and requirements特性與要求的吻合程度More importantly (更重要) to our clients?(對(duì)客戶).Quality Control vs. Quality Assurance(質(zhì)量控制與質(zhì)量保證)Quality control is a series of measurements used to assess the quality of the analytical data質(zhì)量控制是一系列丈量,以評(píng)價(jià)分析數(shù)據(jù)的質(zhì)量How well is the test fulfilling requiremen

3、ts?實(shí)驗(yàn)滿足要求的程度如何?.Quality Control vs. Quality Assurance (質(zhì)量控制與質(zhì)量保證)Quality assurance is a management plan to ensure the integrity of data (a system)質(zhì)量保證是一種管理方案,以確保數(shù)據(jù)的完好性(一種體系)Provides confidence that requirements will be fulfilled為要求能否得到滿足提供自信心.Qualities of Analytical Methods分析方法的質(zhì)量Accuracy(準(zhǔn)確度)Precis

4、ion(精細(xì)度)Selectivity(選擇性)Sensitivity(靈敏度)Linearity(線性)Range(范圍)Robustness / Ruggedness(穩(wěn)健性/穩(wěn)度).Accuracy(準(zhǔn)確度)Degree of agreement between the “true value and the measured value(真值與丈量值之間的一致程度).Accuracy (準(zhǔn)確度)What is the “true value?(什么是真值)Theoretical(實(shí)際值)Consensus(公議值)Accepted / Assigned(可接受/賦值).Accuracy

5、 (準(zhǔn)確度)Expressed as (表示為)the ratio between the assayed value and the “true value (% recovery) 分析值與真值間的比(%回收率)the difference between the assay and the accepted true value (% Error)分析與可接受真值間的差(%誤差).Precision(精細(xì)度)Closeness of agreement between measurements(丈量間的一致程度)Repeatability (r) same conditions, sho

6、rt time interval (same run) short term precision反復(fù)性(r)-一樣條件下短時(shí)間間隔-短期內(nèi)精細(xì)度Intermediate precision same lab different day, analyst, instrument 中間精細(xì)度-同一實(shí)驗(yàn)室不同日期,分析人員,儀器Reproducibility (R) agreement between batches or between labs復(fù)現(xiàn)性-批間或?qū)嶒?yàn)室間的一致性.Precision (精細(xì)度)Expressed as Standard Deviation, Relative Stan

7、dard Deviation or Relative Percent Difference表示為規(guī)范偏向、相對(duì)規(guī)范偏向、相對(duì)百分差.Sensitivity靈敏度Degree of response to a change in analyte concentration resolution被分析物濃度變化的呼應(yīng)變化程度-分辯率Lowest concentration that can be distinguished from background noise detection limit能從背景噪音識(shí)別出的最低濃度-檢測(cè)限.Sensitivity 靈敏度Limit of detectio

8、n vs. Limit of quantification檢測(cè)限與定量限Limit of detection (LOD) is the level that we can say whether an analyte is present or not檢測(cè)限是我們判別被分析物能否存在的含量程度Limit of quantitation (LOQ) is the level that we can quantify the analyte with a specified accuracy (20%)定量限是我們按規(guī)定準(zhǔn)確度20%能對(duì)被分析物量化的含量程度.Selectivity選擇性Abili

9、ty to detect the analyte in a complex matrix檢測(cè)復(fù)雜基體中被析物的才干Ability to exclude non-analyte species from signal經(jīng)過信號(hào)排除非被分析物的才干Usually inversely related to sensitivity通常與靈敏度成反比.Linearity線性Ability to produce a response that is directly proportional to the concentration of the analyte所產(chǎn)生的反響與被分析物濃度成正比的才干Only

10、 holds true within a given range只在給定范圍內(nèi)是真實(shí)的.Linearity 線性Expressed as correlation coefficient (r) or coefficient of determination (r2)表示為相關(guān)系數(shù)(r)或測(cè)定系數(shù)(r2)r2=ssxy2/ssxx ssyy.Range范圍The interval between the highest and lowest concentration for which the method has shown to have suitable levels of accura

11、cy, precision and linearity.在方法具有適宜的準(zhǔn)確度、精細(xì)度和線性的條件下，最高和最低濃度范圍.Robustness穩(wěn)健性Ability of method to be unaffected by small changes in method (internal) conditions方法不因條件的較小變化內(nèi)部而受影響的才干Temperature溫度pHComposition of mobile phase流動(dòng)相組成 Useful when method moves from development to production從方法開發(fā)到運(yùn)用很有用.Ruggedne

12、ss穩(wěn)度Ability of method to be unaffected by external conditions方法不受外界條件影響的才干Different analysts不同的分析人員Different laboratories不同的實(shí)驗(yàn)室Different reagent lots不同批的試劑Different instruments不同的儀器.Ruggedness 穩(wěn)度Useful for technology transfer對(duì)技術(shù)推行很有用.Quality Control Measures質(zhì)量控制手段Calibration standards校準(zhǔn)規(guī)范Blanks空白R(shí)ec

13、overy studies回收率研討Precision studies精細(xì)度研討Sensitivity studies靈敏度研討Detection Limit檢測(cè)限Quantitation limit定量限. Calibration (校準(zhǔn))Directly affects accuracy(直接影響準(zhǔn)確度)Preparation of standards(規(guī)范制備)Matrix (基體)Stability(穩(wěn)定性)Signal type: peak area, peak height信號(hào)類型:峰面積,峰高.Calibration (校準(zhǔn))Calibration curves(校準(zhǔn)曲線)1st

14、 order straight line(一級(jí)-直線)Quadratic acceptable but requires more points(二次方程-可以接受,但需求更多點(diǎn))Internal standards(內(nèi)標(biāo))Refines calibration response(加強(qiáng)校準(zhǔn)呼應(yīng))Added to samples and standards(參與樣品和規(guī)范中)Must behave like the analyte(象被分析物一樣表現(xiàn))Cannot be in samples rare elements, deuterated compounds(樣品中沒有-稀有元素,含重氘的化

15、合物).Calibration (校準(zhǔn))Calibration verification (校準(zhǔn)驗(yàn)證)Repeated calibration standard反復(fù)校準(zhǔn)規(guī)范Interval may be every 20 samples (ICPMS) or once every run (GC-FID)間隔:20個(gè)樣品(ICPMS) 每次(GC-FID).Blanks(空白)Used to monitor contamination(監(jiān)測(cè)污染)Reagent blanks(試劑空白)Instrument blanks(儀器空白)Field blanks(場(chǎng)地空白)Trip blanks(路途

16、空白)Procedural / method blanks(程序/方法空白)Matrix blanks(基體空白)Others?(其它).Recovery Studies回收率研討Used to monitor accuracy監(jiān)測(cè)準(zhǔn)確度Matrix spikes基體加標(biāo)Fortified blanks添加加標(biāo)Surrogates替代Reference Materials參考物質(zhì).Matrix Spikes基體加標(biāo)Known amount of analyte added to sample在樣品中參與知量的被分析物Important with complex matrix對(duì)復(fù)雜基體很重要Ge

17、nerally added prior to extraction process通常在提取前參與Sometimes difficult to know amount to spike ahead of time有時(shí)很難提早知道加標(biāo)量.Fortified Blanks加強(qiáng)空白Analyte spike into reagent blank在試劑空白中參與被分析物標(biāo)樣Carried through sample preparation process在樣品預(yù)備過程中參與.Surrogate替代Compound with similar properties to target analyte與被

18、分析物具有相近特性的化合物Added to all samples (unknowns and QC) but not standards在一切樣品(未知的和QC)中參與，但標(biāo)樣中不加Used to monitor method performance on a sample (matrix) specific basis 應(yīng)基于特定樣品基體，用于監(jiān)測(cè)方法表現(xiàn). Reference Materials參考物質(zhì)Matrix matched materials with known concentration of analytes被分析物知濃度的基體匹配的物質(zhì)May be external or

19、 in-house外部 或室內(nèi)Sources來源NIST (US)NRC (Canada)European Union歐盟Commercial Vendors商業(yè)渠道.Reference Materials參考物質(zhì)Used primarily to monitor accuracy主要用于監(jiān)測(cè)準(zhǔn)確度May be used for other quality 用于其它質(zhì)量目的measures (precision, sensitivity)丈量精細(xì)度、靈敏度Best overall QC?最好的全面質(zhì)量控制？Expensive費(fèi)用高.Precision Studies精細(xì)度研討Duplicate

20、s反復(fù)Field duplicates場(chǎng)地反復(fù)Lab duplicates實(shí)驗(yàn)室反復(fù)Instrument duplicates儀器反復(fù)Inter-lab splits室內(nèi)分樣Used to identify variance in different processes用于識(shí)別不同過程的變異.Sensitivity Studies靈敏度研討Usually performed initially, then periodically thereafter通常最開場(chǎng)要做，以后定期做Multiple replicates of a blank or low-level standard空白或低含量規(guī)

21、范多次反復(fù).Sensitivity Studies靈敏度研討Detection Limit no quantitation檢測(cè)限-非定量Quantitation Limit Accuracy criteria added定量限準(zhǔn)確度準(zhǔn)那么.Sensitivity Studies靈敏度研討Detection Limit 99% certainty that the concentration is greater than zero that the analyte is present in the sample檢測(cè)限99%確定濃度大于0-樣品中有被分析物Uncertainty is high

22、 (+/- 100% or more)不確定度高 +/- 100% 或更高Quantitation Limit定量限Lowest concentration that can be determined with a given accuracy (e.g. 20% relative error)在一定準(zhǔn)確度下如20%相對(duì)誤差可以測(cè)定出的最低濃度.Linearity線性Determined initially and then as needed最開場(chǎng)時(shí)測(cè)定，然后需求時(shí)測(cè)定Dynamic Linear Range relates to detector response動(dòng)態(tài)線性范圍與檢測(cè)器呼應(yīng)

23、有關(guān)Also consider preparation limitations也可以以為是預(yù)備中的限制Solubilities溶解度Extraction efficiencies提取率Derivitizing reactions衍生反響.What do we run as QC?為什么要做質(zhì)量控制It depends on:取決于Type of instrumentation儀器類型Stage of Method Development方法開發(fā)階段Type of analysis分析類型.What do we run as QC?為什么要做質(zhì)量控制Stage of Method Develop

24、ment方法開發(fā)階段Validation確認(rèn)Verification / Qualification驗(yàn)證/判別Routine analysis日常分析.What do we run as QC?為什么要做質(zhì)量控制Type of Analysis分析類型Assay分析Impurities雜質(zhì)Limits限制Content含量Identification識(shí)別.Quality Data Required at Method Validation方法確認(rèn)所需的質(zhì)量數(shù)據(jù)DataRequired所需數(shù)據(jù)I.D.名稱Impurity Testing雜質(zhì)檢測(cè)Assay Content分析含量Quant.量Li

25、mit限Accuracy準(zhǔn)確度NOYESNOYESPrecision精密度NOYESNOYESSelectivity選擇性YESYESYESYESDetection limit檢測(cè)限NOMAYBE可能YESNOQuantitation limit定量限NOYESNOMAYBE可能Linearity線性NOYESNOYESRange范圍NOYESNOYES.Quality Data Required in Routine Analysis日常分析所需質(zhì)量數(shù)據(jù)DataRequired所需數(shù)據(jù)I.D.名稱Impurity Testing雜質(zhì)檢測(cè)Assay Content分析含量Quant.量Limi

26、t限Accuracy準(zhǔn)確度NOYESNOYESPrecision精密度NOYESNOYESSelectivity選擇性NOMAYBE1NOMAYBE1Detection limit檢測(cè)限NONONONOQuantitation limit定量限NOMAYBENOMAYBELinearity線性NOYESNOYESRange范圍NONONONO1 may be required when working in unknown matrix.Review of Quality Assurance質(zhì)量保證概述We will cover內(nèi)容Definition and Description of Q

27、A質(zhì)量保證的定義和描畫Tools in a QA SystemQA體系的工具Proficiency Testing才干驗(yàn)證Certified Reference Materials有證規(guī)范物質(zhì)Validated Methods經(jīng)過確認(rèn)的方法. Quality Assurance質(zhì)量保證Quality Assurance質(zhì)量保證Planned actions designed to provide confidence that quality requirements will be fulfilled為質(zhì)量要求得到滿足提供自信心而設(shè)計(jì)的有方案的活動(dòng)Quality Assurance Syst

28、em質(zhì)量保證體系A(chǔ) set of processes applied within a defined structure to generate desired outcomes在規(guī)定的構(gòu)造內(nèi)產(chǎn)生預(yù)期結(jié)果所采用的一組過程The good management of good science良好的科學(xué)良好的管理.Quality System Components質(zhì)量體系組成Management管理Plan謀劃Performance實(shí)施Do做Assessment評(píng)價(jià)Review評(píng)審.6 Pillars of QA/QCQA/QC的六個(gè)根底Management管理Facilities設(shè)備Perso

29、nnel人員CRMs有證規(guī)范物質(zhì)PTs才干驗(yàn)證Validated Methods經(jīng)確認(rèn)的方法.Proficiency Testing才干驗(yàn)證Provides external assessment of performance為表現(xiàn)提供外部評(píng)審Provides a basis for corrective and preventive action為糾正和預(yù)防措施提供根底.Information Gained搜集信息Comparison of performance against an external standard將表現(xiàn)與外部規(guī)范比較Comparison against past pe

30、rformance與過去的表現(xiàn)比較Comparison against peer (competitor) labs與同行競(jìng)爭(zhēng)者比較Identification of unsatisfactory performers識(shí)別出不稱心的操作者.Types of PT才干驗(yàn)證類型Specific analyte/matrix combination特定被分析物/基體結(jié)合Mercury in fish魚中的汞Benzene in air空氣中的苯Field of analysis場(chǎng)地分析Metals by ICPICP測(cè)金屬Pesticides by GC/MS GC/MS測(cè)殺蟲劑.Samples樣品

31、Sub-sampled from bulk supply從批中抽取樣本Discrete sample split and distributed謹(jǐn)慎分割樣品并分發(fā).Interlaboratory Comparisons實(shí)驗(yàn)室間比對(duì)Collaborative studies協(xié)同研討Certification studies認(rèn)證研討Round-robin studies循環(huán)研討.Selection of PT programsPT方案的選擇Availability of relevant programs能否有相關(guān)方案Organization of relevant programs相關(guān)方案的組織

32、Any program is usually better than nothing只需求方案，總比沒有好.Assessment of PT ProgramsPT方案的評(píng)價(jià)Before committing long-term consider在實(shí)施前應(yīng)思索Statistics used to interpret data解釋結(jié)果的統(tǒng)計(jì)技術(shù)How “true value is determined真值如何確定Theoretical實(shí)際值Referee lab參考實(shí)驗(yàn)室Consensus公議值.Scoring of Participants參與者的評(píng)價(jià)Z scoreZ值Deviation fro

33、m “true value divided by sigma測(cè)得值與真值之差除以Sigma may be an accepted deviation or statistically determined in each round能夠是可接受的偏向或每輪測(cè)試的統(tǒng)計(jì)結(jié)果.ScoringZ-值Generally a Z-score Z-值 2, 3 is considered unsatisfactory離群 scores must be within 2 sigmaZ-值必需在2- 之間.Laboratory Interpretation實(shí)驗(yàn)室的解釋View results in contex

34、t從整體上看結(jié)果Do they agree with in-house QC data能否與室內(nèi)質(zhì)量控制數(shù)據(jù)一致Trend analysis (consider how sigma is determined)趨勢(shì)分析思索是如何確定的Performance of other participants其它參與者的表現(xiàn).Laboratory Interpretation實(shí)驗(yàn)室的解釋Compare methodology and re-calculate if possible比較方法，假設(shè)能夠重新計(jì)算Compare uncertainty against in-house estimates將不確

35、定度與室內(nèi)評(píng)價(jià)比較.Corrective Actions糾正措施Determine when to take action確定何時(shí)采取措施After 1 unsatisfactory score?一個(gè)不稱心結(jié)果After many (3) in one round?一輪中多個(gè)如三個(gè)不稱心結(jié)果After 2 consecutive unsatisfactory scores?延續(xù)二個(gè)不稱心結(jié)果.Corrective Actions糾正措施Always investigate總要調(diào)查Include包括QC data質(zhì)量控制數(shù)據(jù)Calculations, dilutions, transcripti

36、ons計(jì)算、稀釋，謄寫Training status of analyst分析人員培訓(xùn)情況Performance records of equipment設(shè)備運(yùn)轉(zhuǎn)記錄Records of calibrants, reagents etc.校準(zhǔn)品、試劑的記錄等.Corrective Actions糾正措施Formulate action公布措施Execute action實(shí)施措施Check if action was successful檢查措施能否有效.General Considerations幾點(diǎn)思索More emphasis is being placed on PT programs

37、by assessors, regulators and clients評(píng)審員、管理部門和客戶更多強(qiáng)調(diào)PTUse all the information available利用一切可得到的信息Handle PTs like routine samples (as much as possible)象常規(guī)樣品一樣處置PT樣品盡能夠.Third Party Assessment第三方評(píng)審Accreditation Bodies認(rèn)可機(jī)構(gòu)Assess performance against laboratory scope rather than PT program criteria在一定范圍內(nèi)評(píng)審

38、實(shí)驗(yàn)室的表現(xiàn)，而不是PT方案準(zhǔn)那么Consider “fit for purpose思索適宜性.Third Party Assessment第三方評(píng)審Regulators政府管理部門May be involved in development of PT programs能夠參與PT方案的開發(fā)May require assistance from program coordinator to assess results能夠需求方案協(xié)調(diào)人來協(xié)助評(píng)審結(jié)果.Third Party Assessment第三方評(píng)審Customers客戶When using PT results as a perfor

39、mance standard ensure target is realistic當(dāng)運(yùn)用PT結(jié)果作為才干規(guī)范時(shí)，確保目的是現(xiàn)實(shí)的Must investigate program; not just results必需調(diào)查方案，而不僅是結(jié)果.Reference Materials參考物質(zhì)5 types5種類型Pure substance純物質(zhì)Standard solutions and gas mixtures規(guī)范溶液和氣體混合物Matrix RMs基體參考物質(zhì)Physical properties物理特性Reference objects (artifacts)參考目的參考品.Referenc

40、e Materials參考物質(zhì)May be used for 可用于Internal QC內(nèi)部質(zhì)量控制Method validation方法確認(rèn)Calibration校準(zhǔn)Estimating uncertainty評(píng)價(jià)不確定度Training培訓(xùn).Classification分類Certified Reference Materials有證參考物質(zhì)Directly traceable直接溯源Each property has an uncertainty associated with it每一特性有相應(yīng)不確定度Reference material參考物質(zhì)Properties are homogenous and thoroughly characterized to be used for calibration or method assessment特性是均勻的，并完好定值，以用于校準(zhǔn)或方法評(píng)價(jià).Avai