Risk of false conformity decisions due to measurement uncertainty of Active Pharmaceutical Ingredient: A multiparametric evaluation

Abstract Medicines must be subject to physical, chemical, and biological analysis to guarantee their quality, safety, and effectiveness. Despite the efforts to ensure the reliability of analytical results, some uncertainty will always be associated with the measured value, which can lead to false decisions regarding conformity/non-conformity assessment. This work aims to calculate the specific risk of false decisions regarding conformity/non-conformity of acetaminophen oral solution dosage form. The acetaminophen samples from five different manufacturers (A, B, C, D, and E) were subject to an active pharmaceutical ingredient assay, density test, and dose per drop test according to the official compendia. Based on measured values and their respective uncertainties, the risk values were calculated using the Monte Carlo method implemented in an MS Excel spreadsheet. The results for two acetaminophen oral solution samples (C and D) provided an increased total risk value of false acceptance (33.1% and 9.6% for C and D, respectively). On the other hand, the results for the other three acetaminophen samples (A, B, and E) provided a negligible risk of false acceptance (0.004%, 0.025%, and 0.045% for A, B, and E, respectively). This indicates that measurement uncertainty is very relevant when a conformity assessment is carried out, and information on the risks of false decisions is essential to ensure proper decisions.

Multivariate guard-bands and total risk assessment on multiparameter evaluations with correlated and uncorrelated measured values

Abstract The quality, efficacy, and safety of medicines are usually verified by analytical results. Measurement uncertainty is a critical aspect for the reliability of these analytical results. The pharmacopeial compendia usually adopt a simple acceptance rule that does not consider information from measurement uncertainty. In this work, we compared decision-making using simple acceptance and decision rules with the use of guard-band for multiparameter evaluation of ofloxacin ophthalmic solution and acyclovir topical cream. Ciprofloxacin ophthalmic solution and acyclovir topical cream samples were subject to pharmacopeial tests and assays. Multivariate guard-band widths were calculated by multiplying the standard uncertainty (u) by an appropriate multivariate coverage factor (k'). The multivariate coverage factor (k') was obtained by the Monte Carlo method. According to the simple acceptance rule, all the results obtained for ciprofloxacin ophthalmic solution and acyclovir topical cream are within the specification limits. However, the risk of false conformity decisions increases for ciprofloxacin tests. Decisions made using the simple acceptance rule and decision rules with the use of guard-band may differ. The simple acceptance rule may increase the risk of false conformity decisions when the measured value is close to the regulatory specification limits and/or when the measurement uncertainty value is inappropriately high. Nevertheless, the guard-band decision rule will always reduce the risk of false conformity decisions. Therefore, using information on measurement uncertainty in conformity assessment is highly recommended to ensure the proper efficacy, safety, and quality of medicines.

Incerteza de medição associada à contagem microbiana de produtos farmacêuticos / Measurement uncertainty associated with microbial count of pharmaceutical products

A contaminação microbiana pode comprometer a eficácia e a segurança dos produtos farmacêuticos. Os testes de contagem microbiana são utilizados para avaliar a qualidade microbiológica de produtos farmacêuticos não estéreis, exigidos pela maioria dos compêndios farmacopeicos. Apesar disso, raramente é considerada a avaliação da incerteza de medição para testes de contagem microbiana, o que pode levar a falsas decisões quanto à conformidade/nãoconformidade. Neste trabalho avaliamos os efeitos de matriz nos testes de contagem microbiana e sua avaliação de incerteza top-down, e avaliamos a incerteza da medição utilizando a abordagem bottom-up, além de que estimamos os riscos do consumidor ou do produtor devido à incerteza da medição. As incertezas combinada e expandida são calculadas empregando-se a abordagem topdown consideraram a exatidão (recuperação) e a precisão como os principais componentes de incerteza. O componente de incerteza da exatidão foi o mais relevante em 59% das amostras estudadas, enquanto a precisão foi a principal fonte de incerteza em apenas 41% das amostras, sendo observado que quanto maior a interferência da matriz, maior o fator de incerteza e, consequentemente, maior a assimetria para o intervalo em torno da medida. A partir da abordagem bottom-up, foram identificadas e quantificadas três principais fontes de incerteza: fator de diluição, volume plaqueado e contagem das placas. A contribuição dessas fontes de incerteza depende do valor medido da carga microbiana em produtos farmacêuticos, a contribuição do fator de diluição e das incertezas do volume plaqueado aumentam com o aumento do valor medido, enquanto a contribuição da contagem das placas diminui com o aumento do valor medido. Foi possível avaliar o risco de decisões falsas devido à incerteza de medição, por meio das estimativas dos riscos do consumidor ou do produtor. Os riscos foram avaliados utilizando-se o método Monte Carlo. Portanto, foi demonstrado a relevância da avaliação da incerteza de medição para garantir a confiabilidade dos resultados dos testes de contagem microbiana e a apoiar a tomada de decisões quando a avaliação da conformidade/não-conformidade dos produtos farmacêuticos não estéreis

Microbial contamination can compromise the efficacy and safety of pharmaceutical products. Microbial counting tests are used to assess the microbiological quality of non-sterile pharmaceutical products required by most pharmacopoeia compendiums. Despite this, measurement uncertainty assessment for microbial count tests is rarely considered, which can lead to false compliance/non-compliance decisions. In this work we evaluated the matrix effects on microbial counting tests and their top-down uncertainty assessment, and evaluated measurement uncertainty using the bottom-up approach, inaddition to estimating the consumer's or producer's risks due to measurement uncertainty. The combined and expanded uncertainties calculated using the top-down approach considered accuracy (recovery) and accuracy as the main components of uncertainty. The uncertainty component of accuracy was the most relevant in 59% of the samples studied, while accuracy was the main source of uncertainty in only 41% of the samples, being observed that the greater the interference of the matrix, the greater the uncertainty factor and, consequently, the greater the asymmetry for the interval around the measurement. From the bottom-up approach, three main sources of uncertainty were identified and quantified: dilution factor, platelet volume and plaque count. The contribution of these sources of uncertainty depends on the measured value of microbial load in pharmaceutical products, the contribution of the dilution factor and uncertainties of the plated volume increase with the increase in the measured value, while the contribution of plate counting decreases with the increase of the measured value. It was possible to assess the risk of false decisions due to measurement uncertainty by estimating consumer or producer risks. The risks were evaluated using the Monte Carlo method. Therefore, the relevance of measuring uncertainty assessment has been demonstrated to ensure the reliability of microbial count test results and to support decision-making when assessing non-sterile pharmaceutical conformity/non-compliance

Evaluation on measurement uncertainty of correction factors of fluconazole impurities determined by HPLC standard curve method / 中国药科大学学报

@#In this paper, the uncertainties of correction factors of fluconazole impurities determined by HPLC standard curve method were evaluated, and the main common factors affecting the accuracy of standard curve method were found, so as to improve the accuracy of the method.In this study, the corresponding fitting lines of fluconazole and its impurities A, B, C, D, F and I were established respectively, and the ratio of the slope of fitting lines of each impurity and its corresponding principal component was calculated as the correction factor of the impurity.Then on the basis of GUM method, the uncertainty of each impurity correction factor determined by standard curve method was evaluated according to the established uncertainty evaluation scheme of correction factor determination process.The correction factor and uncertainty of fluconazole impurities A, B, C, D, F and I were 1.068 ± 0.046, 0.102 ± 0.005, 0.0582 ± 0.0031, 1.382 ± 0.121, 0.802 ± 0.067 and 1.383 ± 0.119, respectively, and the coverage factor k was 2.Finally, the contribution rate of each uncertainty component was calculated.In the relative combined standard uncertainties urel(f) of fluconazole impurities A, B, C, D, F and I correction factors, the sum of contribution rate of slope uncertainty urel(K) of the linear equation of principal component and its impurity is more than 85%; in the slope uncertainties urel(K) of linear equation, the contribution rates of uncertainties of solution concentration in 8 of 12 data groups are more than 80%, and the contribution rates of uncertainties introduced by reference substance content in solution concentration are about 80%.It can be seen that the preparation of linear solution concentration is the most influential factor in the determination of impurity correction factor by standard curve method, followed by the linear fitting process.In the preparation process of linear solution concentration, the purity of reference substance is the most influential factor, followed by weighing and pipetting times.The conclusion can help the experimenters to better formulate experimental plans and ensure the accuracy of the results when doing similar work.

Desenvolvimento de métodos microbiológicos rápidos (MMRs) para avaliação da potência de agentes antimicrobianos e suas incertezas de medição / Development of rapid microbiological methods (RMMs) for evaluation of potency of antimicrobial agents and their measurement uncertainties

O método de difusão em ágar tem sido utilizado na avaliação da atividade antimicrobiana desde a descoberta da penicilina. Apesar disso, pouco avanço ocorreu no sentido de reduzir o tempo necessário para a determinação dos halos de inibição de crescimento. O objetivo deste projeto foi desenvolver, otimizar e validar métodos microbiológicos rápidos (MMRs) para a avaliação da potência de agentes antimicrobianos, além de identificar, quantificar e avaliar as principais fontes de incerteza associadas à determinação da potência. O projeto foi dividido em quatro etapas: 1) influência da composição do meio de cultura na formação dos halos de inibição; 2) estudo da incerteza de medição associada à determinação da potência de agentes antimicrobianos; 3) desenvolvimento, otimização e validação de métodos microbiológicos rápidos (MMRs) para determinação da potência de agentes antimicrobianos e 4) determinação dos parâmetros envolvidos na formação dos halos de inibição de crescimento e estudo dos mecanismos de difusão e crescimento microbiano. Os resultados deste projeto possibilitaram a redução do tempo necessário para a determinação do tamanho dos halos de inibição. Adicionalmente, contribuiu com a elucidação dos mecanismos de difusão e crescimento microbiano, possibilitando identificar e quantificar as principais fontes de incerteza de medição associadas à formação dos halos de inibição

Agar diffusion method has been used in the evaluation of antimicrobial activity since the discovery of penicillin. Nevertheless, little progress has occurred in order to reduce the time required for the determination of growth inhibition zones. The goal of this project was to develop, optimize and validate rapid microbiological methods (RMMs) for evaluation of potency of antimicrobials, as well as to identify, quantify and assess the main sources of uncertainty associated with potency. The project was divided into four steps: 1) influence of culture medium composition on inhibition zones; 2) study of measurement uncertainty associated with antimicrobials potencies; 3) development, optimization and validation of rapid microbiological methods (RMMs) for the determination of antimicrobials potencies and 4) determination of the parameters involved in the formation of inhibition zones and study of mechanisms of diffusion and microbial growth. The results of this project allowed the reduction of the time required for the determination of inhibition zone sizes. Additionally, it contributed to the elucidation of the mechanisms of diffusion and microbial growth, making it possible to identify and quantify the main sources of measurement uncertainty associated with formation of inhibition zone sizes

Desarrollo de un material de referencia certificado para análisis elemental de agua potable / Development of a certified reference material for elemental analysis of drinking wáter / Desenvolvimento de um material de referência certificado para análise elementar de água potável

Resumen La producción de un material de referencia (MR) es un proceso en el que se realizan estudios relacionados con la preparación, envasado y caracterización (incluye homogeneidad y estabilidad). En este trabajo se presentan los resultados del desarrollo de un MR de agua potable. El envasado se realiza aplicando dos procedimientos (envasado convencional e inmersión). La caracterización se realizó por Absorción Atómica, ICPMS y Cromatografía iónica. La evaluación de homogeneidad del material se realizó para Na, Mg, Ca, Fe, K, Co, Pb, Mo, As, Ni, Se, Cu, Al, Cr Zn y aniones como NO3 - y Cl-. La estabilidad se evaluó a corto (condiciones aceleradas) y largo plazo por ICPMS y CI, además se realizó seguimiento gravimétrico. La homogeneidad y estabilidad se evaluaron con base en su incertidumbre. La incertidumbre asociada a la homogeneidad y estabilidad MR evidenció resultados aceptables para la mayoría de los analitos. Los resultados del seguimiento gravimétrico permitieron detectar pérdidas de masa del material, por lo que se planteó un nuevo esquema para evaluar la estabilidad a través de métodos gravimétricos. Finalmente, se encontró que el MR presenta incertidumbres expandidas entre el 0,93% y el 4,38%, siendo apto para el uso previsto.

Abstract The production of reference materials (RM) is a process that involves carrying out different studies related to the preparation, packaging and chemical stability of the analytes. This paper presents the results of the development of a drinking water RM. The packaging is done by applying two procedures (conventional packaging and immersion). The characterization of this material was carried out through atomic absorption, ICPMS and ion chromatography. The assessment of the homogeneity of the material was carried out for Na, Mg, Ca, Fe, K, Co, Pb, Mo, As, Ni, Se, Cu, Al, Cr Zn and anions as NO3 - y Cl-. The stability studies were evaluated in the short term (accelerated conditions), and long term by ICPMS and IC, and gravimetric monitoring was also performed. Homogeneity and stability were evaluated based on their uncertainty. The uncertainty associated with homogeneity and MR stability evidenced acceptable results for most analytes. The results of the gravimetric monitoring allowed to detect losses of mass of the material, reason why a new scheme was proposed to evaluate the stability through gravimetric methods. Finally, it was found that the RM presents expanded uncertainties between 0,93% and 4,38%, which makes it suitable for the intended use.

Resumo Este artigo apresenta os resultados do desenvolvimento de um MR de água potável. A embalagem é feita aplicando dois procedimentos (embalagem convencional e imersão). A caracterização foi realizada por Absorção Atômica, ICPMS e Cromatografia Iônica. A avaliação da homogeneidade do material foi realizada para Na, Mg, Ca, Fe, K, Co, Pb, Mo, As, Ni, Se, Cu, Al, Cr Zn e ânions como NO3 - y Cl-. A estabilidade foi avaliada em curto prazo (condições aceleradas) e em longo prazo pelo ICPMS e IC, e também foi realizada monitoração gravimétrica. A homogeneidade e estabilidade foram avaliadas com base na incerteza. A incerteza associada à homogeneidade e estabilidade da RM evidenciou resultados aceitáveis para a maioria dos analitos. Os resultados do monitoramento gravimétrico permitiram detectar perdas de massa do material, pelo que foi proposto um novo esquema para avaliar a estabilidade por métodos gravimétricos. Por fim, verificou-se que o RM apresenta incertezas expandidas entre 0,93% e 4,38%, sendo adequado para o uso pretendido.

Uncertainty analysis for detecting methyl mercury in fish tissue with liquid chromatography-atomic fluorescence spectrometry / 中国医学装备

Objective: To establish a method of liquid chromatography-atomic fluorescence spectrometry (LC-AFS), and carry out uncertainty analysis of detecting methyl mercury in fish tissue. Methods: LC-AFS method was adopted to determine the content of methyl mercury in fish tissue. And the theory of assessment and expression about uncertainty measurement based on JJF1059.1-2012 of State Administration for Market Regulation was applied to analyze the source of factors that affect its uncertainty. Through evaluated various factors of uncertainty and calculated and combined uncertainty to obtain the extended uncertainty of measurement results. Results: The content of methyl mercury in fish tissue by using LC-AFS wasω=(817.94±105.02)μg/kg (k=2, confidence level was 95%). Conclusion: The measurement uncertainty assessment can be used in the uncertainty analysis that LC-AFS measure content of methyl mercury in fish tissue. Therefore, the results are more reliable.

Measurement uncertainty of dissolution test of acetaminophen immediate release tablets using Monte Carlo simulations

ABSTRACT Analytical results are widely used to assess batch-by-batch conformity, pharmaceutical equivalence, as well as in the development of drug products. Despite this, few papers describing the measurement uncertainty estimation associated with these results were found in the literature. Here, we described a simple procedure used for estimating measurement uncertainty associated with the dissolution test of acetaminophen tablets. A fractionate factorial design was used to define a mathematical model that explains the amount of acetaminophen dissolved (%) as a function of time of dissolution (from 20 to 40 minutes), volume of dissolution media (from 800 to 1000 mL), pH of dissolution media (from 2.0 to 6.8), and rotation speed (from 40 to 60 rpm). Using Monte Carlo simulations, we estimated measurement uncertainty for dissolution test of acetaminophen tablets (95.2 ± 1.0%), with a 95% confidence level. Rotation speed was the most important source of uncertainty, contributing about 96.2% of overall uncertainty. Finally, it is important to note that the uncertainty calculated in this paper reflects the expected uncertainty to the dissolution test, and does not consider variations in the content of acetaminophen.

Further Understanding of Measurement Uncertainty in Clinical Laboratory Medicine / 现代检验医学杂志

In clinical laboratory medicine,measurement uncertainty (MU) is a fixed property of testing results in the measuring system.As an important part of ISO 15189,it is necessary for clinical laboratories to determine MU during the period of validation and verification for each measurement procedure and to review MU over time.Now,testing reports provided by clinical laboratories usually do not offer MU,but some clinical laboratories have already estimated MU in their routine work.Estimation andmonitoring of MU can help clinical laboratories offering more accurate results and provide objective tools for clinicians used in result intcrpretatinn.Generally,result interpretation can be achieved by the result comparison with three main comparators,including a previous result from the same patient,a population reference interval and a clinical decision point.The means of true value and the components contributing to the estimation of MU are both different when the com parison is conducted between testing results and different comparators,so the optimum estimation method of MU is accordingly different,which will subsequently affect the MU value and the determination of clinical decisions.Obviously,depending on the actual clinical uses,laboratories can choose appropriate comparators to the result interpretation and the determination of optimum estimation method of MU.For different clinical uses (diagnosis or monitoring) of the same mearurands,the adoption of different estimation methods should be used to acq uire reasonable MU.By interpreting the concept,characteristics,estimation,and uses of MU,as well as explaining how three main comparison methods of results exploit their own traceable chain to get MU,this paper intends to help clinical laboratories get further understanding of the importancc of MU and provide guidance for the MU estimation in routine work.

Evaluation on measurement uncertainty of detecting procedure of amino acids and carnitines by using non-derivatized tandem mass spectrometry method / 国际检验医学杂志

Objective To evaluate the measurement uncertainty of the detecting procedure of amino acids and carnitines by the Waters ACQUITY TQD tandem mass spectrometer and PerkinElmer NeoBaseTM non‐derivatized MSMS kit ,and to discuss the meaning of evaluation .Methods According to the method provided by the Medical Laboratories‐Evaluation and Expression of Measurement Uncertainty ,the internal quality control was detected by using two different batch codes of kit for 20 d ,once before and after the routine sample detection on each working day ,the detector were randomly changed ,and then the measurement uncer‐tainty introduced by measurement reproducibility was calculated;the amino acid external assessment quality control data in 20 times of neonatal hereditary metabolic disease tandem mass spectrometry screening provided by the National Center for Clinical Laborato‐ry in 2014 and 2015 ,and the same and 16 times of carnitines external assessment quality control data were performed the statistics , and then the measurement uncertainty introduced by bias was calculated .Next the relative standard uncertainty and the relative ex‐panded uncertainty according to the measurement uncertainty introduced by bias and measurement reproducibility were calculated . The allowed total error indicators of amino acid and carnitines external quality assessment in the neonatal hereditary metabolic dis‐ease tandem mass spectrometry screening by the National Center for Clinical Laboratory were used as the target expanded uncer‐tainty .Results The relative expanded uncertainties of citrulline ,methionine ,phenylalanine ,propionyl carnitine ,octanoyl carnitine , dodecanoyl carnitine ,palmitoyl carnitine and octadecanoyl carnitine were 19 .1% -26 .1% (k=2) ,which were smaller than the tar‐get uncertainty .The relative expanded uncertainties of leucine ,tyrosine ,valine ,free carnitine were 31 .0% -43 .3% (k=2) ,which were greater than the target uncertainty .The uncertainty of isovaleryl carnitine needed to be estimated separately .Conclusion As‐sessing the measurement uncertainty of the detecting procedure of amino acids and carnitines by the non‐derivatized tandem mass spectrometer method can not only provide an opportunity for continuously improving the detection quality ,but also can help the ex‐perimental technique staffs to interpret the test data correctly and the clinician to use the detection reports correctly .

Evaluation of uncertainty in determination of ethanol in human blood by auto HS-GC with internal standard curve method / 中国法医学杂志

ObjectiveTo evaluate the uncertainty for the determination of ethanol in human blood by auto-headspace gas chromatography (HS-GC) with internal standard curve method.Methods Each source of uncertainty, arising from the procedure of testing, was analyzed and conifrmed according to the guidelines of the uncertainty in measurement . After each uncertainty component was quantized, the combined standard uncertainty and the expanded uncertainty of the result were calculated.Results The relative uncertainty brought from the measurement repeatability, standard solution of the ethanol, the sample of blood, internal standard solution of the tert-butyl alcohol, the calibration cure, gas chromatography were 3.4%,0.71%,0.61%,0.41%,1.1% and 1.3% respectively; the relative expanded uncertainty of ethanol in blood was 3.9%.Conclusion The measurement uncertainty of the concentration of ethanol was came primarily from the measurement repeatability of sample, HS-GC and standard curve of ethanol.

Evaluation of Measurement Uncertainty for the Content of Bisacodyl Enteric-coated Tablet by HPLC / 中国药房

OBJECTIVE:To a evaluation method for the measurement uncertainty for the content of Bisacodyl enteric-coated tablet. METHODS:HPLC external standard method was conducted for content determination of Bisacodyl enteric-coated tablet, and mathematical model for uncertainty evaluation was established to systematically analyze and evaluate the influential factors in processes of solution preparation and instrument measurement. RESULTS:HPLC external standard method showed the content was 97.8%,confidence probability was 95%,expanded uncertainty was 2.8%,and determination result was (97.8 ± 2.8)%,k=2. CONCLUSIONS:The established method is suitable for the evaluation of measurement uncertainty for the content of Bisacodyl en-teric-coated tablet. Regularly calibrated verification for HPLC equipment and strict control of the weighing process will help to im-prove the accuracy measured by HPLC.

Composing and evaluating the measurement uncertainty of two kinds of chemiluminescence detection system / 中华核医学与分子影像杂志

Objective To compose and evaluate the measurement uncertainty of two kinds of chemiluminescence detection system using different methods.Methods The measurement uncertainty was composed by 4 different methods:(1) U 1％ was composed of within-run CV(CVw ％),between-run CV(CVB ％)and bias (CVBias ％);(2) U2％ was composed of CVB ％ and uncertainty of calibration (CVcal ％);(3) U3％ was composed of CVW％,CVs％ and CVcal％;(4) U4％ was composed of CVW％,CVB％,CVBias％ and CVcal％.The measurement uncertainty of Architect i2000SR system (Abbott,USA) and DXI800 system (Beckman,USA) was assessed.Pearson correlation analysis,Spearman correlation analysis,Paried t test and Mann-Whitney u test were performed to analyze the data.Results For Architect i2000SR system,U1％,U2％,U3％ and U4％ were significantly correlated (r=0.727-0.988,all P＜0.05),U3％ and U2％ were significantly different (t =6.88,P＜0.05),U4％ and U1％ were significantly different (t =6.21,P＜0.05).For DXI800 system,U1％,U2％,U3％ and U4％ were also significantly correlated (r =0.608-0.975,all P＜0.05),no significant difference was found between U3％ and U2％ (z=-1.33,P＞0.05),or between U4％ and U 1％ (z =-1.04,P＞ 0.05);the expanded measurement uncertainty was correlated with CVW％,CVB％,CVBias％(rs=0.653-0.912,all P＜0.05),but not with CVcal％(rs=0.548,P＞0.05).Conclusions For Architect i2000SR system,the fourth method is more proper to compose the measurement uncertainty (U4％).For DXI800 system,the first method is more appropriate (U1％).According to the contribution of different components to the measurement uncertainty,the measurement quality could be improved by reducing the imprecision and bias.

Total Error and Measurement Uncertainty in Clinical Laboratory Medicine / 现代检验医学杂志

In the clinical laboratory medicine,the measurement uncertainty (MU)is a relatively new concept.Over the years, experts of clinical laboratory medicine from all over the world made a great number of further researches and promote the development of MU,which led clinical laboratories to pay more and more attention to the meanings and functions of MU at the same time.However,because of the habitual using of the total error (TE)in clinical laboratories and similarities between concepts of MU and TE which easily resulted in confusion,a lot of laboratories still cannot completely accept MU.By explai-ning concepts of TE and MU and analyzing the pros and cons of models of TE and MU as well as their functions,the obj ec-tive of this paper is to help clinical laboratories make further comprehensions of TE and MU and understand how to properly use them in practice.

Evaluation on measurement uncertainty of blood routine examination / 国际检验医学杂志

Objective To explore the feasibility of measurement uncertainty in complete blood count using internal quality con-trol(IQC) data associated with Sysmex Network Communication System(SNCS) comparative data .Methods Complete blood count assay including white blood cell(WBC) count ,red blood cell(RBC) count ,hemoglobin(Hb) determination ,hematocrit(HCT) values and platelet(PLT) count were involved to evaluate measurement uncertainty according to the instruction of CNAS-TRL-001 .Meas-urement uncertainty evaluation was established by internal measurement reproducibility using IQC data ,and standard measurement uncertainty by bias using proficiency testing(PT) data and SNCS data ,followed by relative combined standard measurement uncer-tainty and relative expanded measurement uncertainty was calculated .Meanwhile ,the measurement uncertainty was compared by u-sing PT data and SNAS comparative data .Results Relative expanded measurement uncertainty of the above mentioned index by u-sing IQC data associated with PT data was the following :WBC(10 .02% ,7 .24% ,7 .04% ,from level 1 to level 3 respectively) ,RBC (2 .40% ,1 .72% ,1 .92% ,from level 1 to level 3 respectively) ,Hb(3 .54% ,2 .56% ,2 .50% ,from level 1 to level 3 respectively) , HCT(4 .12% ,3 .18% ,2 .86% ,from level 1 to level 3 respectively) ,PLT(15 .36% ,8 .86% ,7 .94% ,from level 1 to level 3 respec-tively) .Relative expanded measurement uncertainty of the above mentioned index by using IQC data associated with SNCS compar-ative data was the following :WBC(11 .66% ,7 .34% ,6 .40% ,from level 1 to level 3 respectively) ,RBC(2 .26% ,1 .60% ,1 .64%from level 1 to level 3 respectively) ,Hb(3 .36% ,2 .36% ,2 .10% ,from level 1 to level 3 respectively) ,HCT (3 .36% ,3 .04% , 3 .18% ,from level 1 to level 3 respectively) ,PLT (13 .34% ,8 .36% ,7 .14% ,from level 1 to level 3 respectively) .Conclusion Measurement uncertainty in complete blood cell could be estimated by using IQC data associated with SNCS comparative data , which is in accord with the instrument of target measurement uncertainty .

Measurement uncertainty evaluation of 23 clinical biochemical items by top-down method / 医疗卫生装备

To evaluate the measurement uncertainty of 23 items of clinical biochemistry. Internal quality control and external quality assessment were used to determine the uncertainty and standard uncertainty for the 23 items detected by Hitachi 7600 automatic biochemical analyzer. The uncertainties met the requirements of CLIA'88 for allowable error before correction except those of Cl-, P, TCH and TG, and correction made those of P, TCH and TG satisfy the requirements. The top-down method contributes to the understanding of the uncertainty of clinical biochemical items, while further efforts have to be performed for the uncertainty assessment standard.

Comparison of 13 emergency biochemical test items′measurement uncertainty between two biochemical analyzers / 国际检验医学杂志

Objective To investigate the method and application of measurement uncertainty in clinical biochemical tests .Meth-ods The synthetic uncertainty and expanding uncertainty of 13 emergency biochemical tests items were compared between Hitachi 7600 and Beckman DXC800 automatic biochemical analyzer by usingmodel method.The test items included aspartate aminotrans-ferase ,total protein ,albumin ,glucose ,urea ,creatinine ,creatine kinase ,lactate dehydrogenase ,amylase ,potassium ,sodium ,calcium and chloride .Results Measurement uncertainty of aspartate aminotransferase and lactate dehydrogenase were 3 .66% and 3 .51%respectively ,which were the top two on Hitachi 7600 analyzer ;measurement uncertainty of calcium and creatinine were 4 .00% and 3 .90% respectively ,which were the top two on Beckman DXC800 .Compared between the two analyzers ,the test item with the lar-gest difference of measurement uncertainty was sodium(2 .62% ) ,and the second was creatinine(2 .40% ) .The difference of meas-urement uncertainty of the 13 emergency biochemical test items between the two analyzers were relatively small .Conclusion The two analyzer both have good performance ,Model methodis suitable for the evaluation of regular test items′measurement uncer-tainty in clinical biochemical laboratory .

Evaluation of measurement uncertainty in routine coagulation assays in medical laboratory / 国际检验医学杂志

Objective To explore the application of evaluation of measurement uncertainty in routine coagulation assays based on the data of internal quality control (IQC) and results of external quality assessment (EQA) .Methods Data of clinical coagulation assays of clinical laboratory of Xiangyang city hospital were collected ,Which came from six months of IQC and 3 times of EQA of ministry of health clinical laboratory center from 2012 to 2013 .The combined and expanded uncertainties of 3 measurements(PT , APTT and Fbg) were evaluated according to CNAS top-downapproach .Results When PT were in 12 .72 s and 21 .04 s ,its ex-panded uncertainty were 1 .06 s and 1 .96 s ,and APTT in 36 .6 s and 50 .6 s were 2 .59 s and 5 .30 s ,and Fbg in 3 .32 g/L was 0 .30 g/L .Conclusion Evaluation of measurement uncertainty by using internal quality control data and EQA results for routine coagula-tion detection index is economical and practical and acceptable way ,with good clinical practice .

Evaluation of Measurement Uncertainty of 2 2 Clinical Chemistry Assays / 现代检验医学杂志

Objective To calculate the measurement uncertainty of clinical chemical analytes according to the internal quality control (IQC)and external quality assessment (EQA)data in clinical laboratory.Methods Collected the IQC data from January to June 2013 and EQA data between 2012~2014 of clinical chemistry in clinical laboratory.Calculated the measure-ment uncertainty and extended uncertainty according to the Nordtest criteria.Results It was effective to evaluate the uncer-tainty using IQC and EQA data.ALP ranked the highest extended uncertainty and Na+ ranked the lowest uncertainty.The range of uncertainty varies greatly,electrolyte 4.27~18.16,enzyme 8.12~24.88,small molecular 4.88~12.44,protein and lipids 4.78~13.1.Conclusion The evaluation of clinical chemistry uncertainty by IQC and EQA data is simple and practi-cal,which is beneficial for assurancing the measurement accuracy.

Analysis of Measurement Uncertainty in Determination of Irbesartan Tablets by HPLC / 中国药师

Objective:To find out the impacting factors in uncertainty by analyzing the measurement uncertainty in the determina-tion of irbesartan tablets by HPLC and provide the evidence for the measurement evaluation. Methods:A mathematic model for calcu-lating uncertainty was established, and every component in the uncertainty was assessed. Results:The expanded standard uncertainty for the HPLC determination was 2. 4%. Conclusion:The measurement uncertainty of the experiment is mainly caused by the measur-ing method.