External Quality Control Assessment Research Articles

Targeted ultra performance liquid chromatography tandem mass spectrometry procedures for the diagnosis of inborn errors of metabolism: validation through ERNDIM external quality assessment schemes.

Early diagnosis of inborn errors of metabolism (IEM) is crucial to ensure early detection of conditions which are treatable. This study reports on targeted metabolomic procedures for the diagnosis of IEM of amino acids, acylcarnitines, creatine/guanidinoacetate, purines/pyrimidines and oligosaccharides, and describes its validation through external quality assessment schemes (EQA). Analysis was performed on a Waters ACQUITY UPLC H-class system coupled to a Waters Xevo triple-quadrupole (TQD) mass spectrometer, operating in both positive and negative electrospray ionization mode. Chromatographic separation was performed on a CORTECS C18 column (2.1×150, 1.6 µm). Data were collected by multiple reaction monitoring. The internal and EQA results were generally adequate, with a few exceptions. We calculated the relative measurement error (RME) and only a few metabolites displayed a RME higher than 30 % (asparagine and some acylcarnitine species). For oligosaccharides, semi-quantitative analysis of an educational panel clearly identified the 8 different diseases included. Overall, we have validated our analytical system through an external quality control assessment. This validation will contribute to harmonization between laboratories, thus improving identification and management of patients with IEM.

HbA1c and biomarkers of diabetes mellitus in Clinical Chemistry and Laboratory Medicine: ten years after.

Since its discovery in the late 1960s, HbA1c has proven to be a major biomarker of diabetes mellitus survey and diagnosis. Other biomarkers have also been described using classical laboratory methods or more innovative, non-invasive ones. All biomarkers of diabetes, including the historical glucose assay, have well-controlled strengths and limitations, determining their indications in clinical use. They all request high quality preanalytical and analytical methodologies, necessitating a strict evaluation of their performances by external quality control assessment trials. Specific requirements are needed for point-of-care testing technologies. This general overview, which describes how old and new tools of diabetes mellitus biological survey have evolved over the last decade, has been built through the prism of papers published in Clinical Chemistry and Laboratory Medicine during this period.

A practical approach example to measurement uncertainty: Evaluation of 26 immunoassay parameters.

IntroductionMeasurement uncertainty is a non-negative parameter that characterizes the distribution of all values appropriate to the measured size and is associated with the measured result. In this study, we aimed to compare the results with various suggestions and produce more qualified results by calculating the measurement uncertainties of the immunoassays like fertility hormones, drug concentration tests, cardiac markers, thyroid function tests and tumour markers.Materials and methodsUncertainty calculation was made in accordance with the top-down approach according to Nordtest guide. The 12-month study of internal and external quality assessment results were used. The parameters of drug concentration tests were performed on the Abbott Architect c8000, other hormones/markers on the i2000 of the same brand.ResultsFactors that increased the measurement uncertainty of a test were due to external quality control data. The calculations showed that 13 of 26 parameters satisfied quality requirements. The highest uncertainty value, with 28% belonged to cancer antigen 19-9 test. The lowest value was calculated for prolactin with 8.3%. Dehydroepiandrosterone sulfate and phenytoin performed poorly in terms of measurement uncertainty, although internal and external quality control assessment results were considered favourable for both.ConclusionIt is recommended that the concept of measurement uncertainty, which plays an important role in the total quality performance of the laboratory, should be followed up by the clinical laboratory experts at certain time intervals and should be increased the awareness of clinicians about the subject.

Anti‐PF4 testing for vaccine‐induced immune thrombocytopenia and thrombosis and heparin induced thrombocytopenia: Results from a UK National External Quality Assessment Scheme exercise April 2021

BackgroundVaccine‐induced immune thrombocytopenia and thrombosis (VITT) following the administration of the AstraZeneca (AZ) ChAdOx1 nCOV‐19 vaccine has recently been reported. The associated clinical and laboratory features have included thrombosis at unusual sites, thrombocytopenia, and raised D‐dimers with positivity for IgG anti‐platelet factor 4 (PF4) antibodies. ObjectivesA UK National External Quality Control Assessment Scheme external quality control exercise was carried out by distributing liquid and lyophilized samples from a subject with VITT, a pool of samples from subjects with classical heparin‐induced thrombocytopenia (HIT), and a non‐VITT/non‐HIT case to 85 centers performing HIT testing. MethodsParticipating centers employed their locally validated testing methods for HIT assays. ResultsThe lyophilized and liquid samples were found to be commutable for the ELISA assays used in the detection of anti‐PF4 antibodies. The Aeskulisa, Stago, Hyphen, and LIFECODES anti‐PF4 ELISA assays successfully detected the VITT antibody, whereas the Acustar HIT, Werfen LIA, and the Stago STIC assays did not. ConclusionIt is important that clinical and laboratory teams are aware of the limitations of some anti‐PF4 assays when using them to aid diagnosis of VITT syndrome.

Performance of factor IX extended half‐life product measurements in external quality control assessment programs

BackgroundPatients with hemophilia B are increasingly treated with extended half‐life (EHL) factor IX (FIX) concentrates. For the laboratory, introduction of these EHL concentrates presents a major challenge. To understand the variation in FIX activity levels, all available diagnostic assays need to be directly compared. MethodsThe ECAT, UKNEQAS, and RCPAQAP have collaboratively performed a global survey to evaluate the quality of FIX measurements using FIX deficient plasma samples spiked with recombinant FIX (rFIX), rFIXFP, rFIXFc, and N9‐GP to levels at typical FIX trough (6 IU/dL) and peak levels (60 IU/dL). Participants were asked to use their routine protocols, using one‐stage assays (OSA) or chromogenic assays (CA). ResultsIn samples spiked with 6 IU/dL product, median (25%‐75% range) FIX activity levels (OSA), were 8.0 IU/dL (7.0‐9.2) for rFIX, 6.0 IU/dL (4.0‐7.1) for rFIXFP, 6.6 IU/dL (5.5‐8.0) for rFIXFc, and 4.9 IU/dL (3.5‐8.4) for N9‐GP. In samples spiked with 60 IU/dL, FIX activity levels measured (using OSA) was 63.0 IU/dL (59.9‐67.0) for rFIX, 42.5 IU/dL (28.2‐47.0) for rFIXFP, 50.0 IU/dL (45.0‐55.0) for rFIXFc, and 34.0 IU/dL (24.8‐67.5) for N9‐GP. Considerable differences were observed between reagents for all samples. With CA, there was also quite some variation, but no differences between reagents. ConclusionLarge variation is observed in the measurement of FIX activity levels after administration of rFIX and EHL FIX products. For N9‐GP, most silica‐based assays show especially high levels. It is essential to standardize and improve reliability of measurements of these concentrates as diagnosis and treatment monitoring is based on these results.

Drug-resistant enteric fever worldwide, 1990 to 2018: a systematic review and meta-analysis

BackgroundAntimicrobial resistance (AMR) is an increasing threat to global health. There are > 14 million cases of enteric fever every year and > 135,000 deaths. The disease is primarily controlled by antimicrobial treatment, but this is becoming increasingly difficult due to AMR. Our objectives were to assess the prevalence and geographic distribution of AMR in Salmonella enterica serovars Typhi and Paratyphi A infections globally, to evaluate the extent of the problem, and to facilitate the creation of geospatial maps of AMR prevalence to help targeted public health intervention.MethodsWe performed a systematic review of the literature by searching seven databases for studies published between 1990 and 2018. We recategorised isolates to allow the analysis of fluoroquinolone resistance trends over the study period. The prevalence of multidrug resistance (MDR) and fluoroquinolone non-susceptibility (FQNS) in individual studies was illustrated by forest plots, and a random effects meta-analysis was performed, stratified by Global Burden of Disease (GBD) region and 5-year time period. Heterogeneity was assessed using the I2 statistics. We present a descriptive analysis of ceftriaxone and azithromycin resistance.FindingsWe identified 4557 articles, of which 384, comprising 124,347 isolates (94,616 S. Typhi and 29,731 S. Paratyphi A) met the pre-specified inclusion criteria. The majority (276/384; 72%) of studies were from South Asia; 40 (10%) articles were identified from Sub-Saharan Africa. With the exception of MDR S. Typhi in South Asia, which declined between 1990 and 2018, and MDR S. Paratyphi A, which remained at low levels, resistance trends worsened for all antimicrobials in all regions. We identified several data gaps in Africa and the Middle East. Incomplete reporting of antimicrobial susceptibility testing (AST) and lack of quality assurance were identified.InterpretationDrug-resistant enteric fever is widespread in low- and middle-income countries, and the situation is worsening. It is essential that public health and clinical measures, which include improvements in water quality and sanitation, the deployment of S. Typhi vaccination, and an informed choice of treatment are implemented. However, there is no licenced vaccine for S. Paratyphi A. The standardised reporting of AST data and rollout of external quality control assessment are urgently needed to facilitate evidence-based policy and practice.Trial registrationPROSPERO CRD42018029432.

НОРМАТИВНО–ПРАВОВІ АКТИ ЩОДО БЕЗПЕЧНОСТІ І ЯКОСТІ ХАРЧОВИХ ПРОДУКТІВ

The analysis of legislation on the safety and quality of food. Under the conditions of accession of any country to international structures prerequisite – the certification and accreditation of workplaces, equipment and laboratory staff in accordance with the requirements of GLP (Good laboratory practice).Analysis of relevant documentation, namely Council Directive 93/99 EEC of 29 October 1993 on additional measures for the official control of foodstuffs, Decision 98/179 EC on laboratories conducting official control, indicates the need for accreditation in accordance with ISO ISO / IEC 17025: 2006 since January 2002. In accordance with Decision 98/179 EC for approved laboratories is mandatory participation in an internationally recognized external quality control assessment and accreditation scheme. Moreover, approved laboratories must prove their competence in the course of regular and successful participation in relevant professional testing schemes recognized or organized by the national reference laboratory or the Community reference laboratory.According to international requirements for food product quality control only insufficient, since it can not guarantee its complete safety. It is necessary to introduce new safety management system and product quality in the modern production process.

Advantages and disadvantages of technologies for HER2 testing in breast cancer specimens.

Human epidermal growth factor receptor 2 (HER2) plays a central role as a prognostic and predictive marker in breast cancer specimens. Reliable HER2 evaluation is central to determine the eligibility of patients with breast cancer to targeted anti-HER2 therapies such as trastuzumab and lapatinib. Presently, several methods exist for the determination of HER2 status at different levels (protein, RNA, and DNA level). In this review, we discuss the main advantages and disadvantages of the techniques developed so far for the evaluation of HER2 status in breast cancer specimens. Each technique has its own advantages and disadvantages. It is therefore not surprising that no consensus has been reached so far on which technique is the best for the determination of HER2 status. Currently, emphasis must be put on standardization of procedures, internal and external quality control assessment, and competency evaluation of already existing methods to ensure accurate, reliable, and clinically meaningful test results. Development of new robust and accurate diagnostic assays should also be encouraged. In addition, large clinical trials are warranted to identify the technique that most reliably predicts a positive response to anti-HER2 drugs.

International external quality control assessment for the serological diagnosis of dengue infections.

BackgroundDengue is endemic to the tropics and subtropics, and the most frequent of arthropod-borne viral diseases. Reliable diagnosis of dengue infection is important not only in clinical care but also in disease surveillance, the control of outbreaks, and the development of new vaccines. The diagnosis of dengue infection is usually established by a variety of commercial or in-house serological protocols. The European Network for the Diagnostics of Imported Viral Diseases (ENIVD) recognized the need to survey the accuracy of dengue serological diagnostics in current use, and organized an external quality assurance (EQA) study of dengue serological practice in diagnostic laboratories.MethodsA 15-sample panel, consisting of sera reactive against dengue plus specificity and negative controls, was sent to 48 laboratories for serological testing. The results returned by the participating laboratories were anonymized, scored, and subjected to comparison and statistical analysis.ResultsTen laboratories rated all samples correctly with regard to IgM, and only three achieved the full score for IgG detection. The main handicaps in assay performance were suboptimal sensitivity of in-house IgM detection protocols by comparison with better-performing commercial ELISA tests, and the presence of IgG cross-reactivity with heterologous flaviviruses. Differences of detail in the methodology of dengue IgG antibody detection appear to underlie the disparities in accuracy observed between laboratories.ConclusionThis EQA study demonstrates that there is room for many laboratories to improve sensitivity in the detection of anti-dengue virus IgM antibodies, against the benchmark set by commercial antibody capture ELISA tests. The EQA shows also that cross-reactivity is a continuing issue, and IgG detection protocols must be optimized to increase their specificity.Electronic supplementary materialThe online version of this article (doi:10.1186/s12879-015-0877-0) contains supplementary material, which is available to authorized users.

Trueness in the measurement of haemoglobin: consensus or reference method?

For the measurement of haemoglobin a reference method exists: the haemiglobincyanide method. However, a Dutch external quality assessment organization does not use this method in the evaluation of trueness of results. The aim of this work was to assess whether trueness was compromised by the use of a consensus value. Five Cell Dyn Sapphires (Abbott) in three independent locations were used to measure haemoglobin concentration. Results were compared to the reference method (haemiglobincyanide). Patient samples with a distribution over clinically relevant concentrations (Hb 2.5-10.2 mmol/L) were used next to samples from external quality assessment rounds. Passing and Bablok regression analysis and Bland-Altman plots were used to evaluate any systematic deviation. Results measured on the Cell Dyn Sapphires deviated significantly from the results obtained with the reference method. Remarkably, consensus results from external quality control samples also deviated significantly from the reference method. A significant negative bias exists in the measurement of haemoglobin on Cell Dyn Sapphires. Additionally, the consensus value as reported in external quality control assessment also shows an even greater significant negative bias compared to the reference method. As a reference method is available, external quality assessment would benefit from using this method instead of a consensus value to evaluate trueness.

The problems of proteinuria measurement in urine with presence of Bence Jones protein

Objectives Protein concentration measurement in the urine can be problematic in the presence of Bence Jones protein. We have carried out an external quality control assessment with the participation of 79 clinical biochemistry laboratories from the Czech Republic and Slovakia. Design and methods The laboratories received a reference urine sample obtained from a patient with multiple myeloma and lambda free light chain proteinuria and were asked to type the paraprotein using immunofixation and to measure total urinary protein using their established method, most commonly turbidimetry, pyrogallol red assay, and biuret assay. Results There was a very wide inter-laboratory variability in the protein concentration readouts with up to three-fold difference in some cases. High-resolution two-dimensional electrophoresis and linear mass spectrometry showed that a high proportion of the urinary paraprotein was composed of lambda light chain fragments with molecular weight of 12 kDa. Conclusions Our results highlight the challenges of reliable and reproducible measurement of urinary protein concentration in the presence of Bence Jones protein.

2nd International External Quality Control Assessment for the Molecular Diagnosis of Dengue Infections

BackgroundCurrently dengue viruses (DENV) pose an increasing threat to over 2.5 billion people in over 100 tropical and sub-tropical countries worldwide. International air travel is facilitating rapid global movement of DENV, increasing the risk of severe dengue epidemics by introducing different serotypes. Accurate diagnosis is critical for early initiation of preventive measures. Different reverse transcriptase PCR (RT-PCR) methods are available, which should be evaluated and standardized. Epidemiological and laboratory-based surveillance is required to monitor and guide dengue prevention and control programmes, i.e., by mosquito control or possible vaccination (as soon as an effective and safe vaccine becomes available).ObjectiveThe purpose of the external quality assurance (EQA) study described is to assess the efficiency and accuracy of dengue molecular diagnosis methods applied by expert laboratories.Study DesignA panel of 12 human plasma samples was distributed and tested for DENV-specific RNA. The panel comprised 9 samples spiked with different DENV serotypes (DENV-1 to DENV-4), including 10-fold dilution series of DENV-1 and DENV-3. Two specificity controls consisted of a sample with a pool of 4 other flaviviruses and a sample with chikungunya virus. A negative control sample was also included.ResultsThirty-seven laboratories (from Europe, Middle East Asia, Asia, the Americas/Caribbean, and Africa) participated in this EQA study, and reports including 46 sets of results were returned. Performance among laboratories varied according to methodologies used. Only 5 (10.9%) data sets met all criteria with optimal performance, and 4 (8.7%) with acceptable performance, while 37 (80.4%) reported results showed the need for improvement regarding accomplishment of dengue molecular diagnosis. Failures were mainly due to lack of sensitivity and the presence of false positives.ConclusionsThe EQA provides information on each laboratory's efficacy of RT-PCR techniques for dengue diagnosis and indicates for most laboratories an urgent need to improve sensitivity and specificity.

Research of applicability of control samples in measurement of whole blood viscosity

Objective To exlore the influence of internal quality control and external quality control assessment(EQA) resulting from applicability of control samples in measurement of whole blood viscosity (WBV) through the analysis and comparison of applicability of 1 non-Newtonian fluid internal quality control sample in 3 viscometers. Methods Viscometer B, C and D were used to measure WBV of 30 blood samples in parallel under the shear rate(SR) of 1 s-1,30 s-1 and 200 s-1, then the blood SR-WBV curves of 3 viscometers were drawn according to the results. At the same time, viscometers B, C and D were used respectively to determine the WBV of control A 10 times in one day, then the control A SR-WBV curves were mapped. Three viscometers were used to measure the manufactory control samples and control A 5 times in one day for 4 days. Four groups of daily values of manufactory control samples and control A of each instrument were used to carry out F test to calculate whether 4 daily values are difference. Finally, the control A was dispensed in 49 laboratories nationwide chosen for measurement. On the basis of viscometer used, 20 laboratories were classified as group B, 20 laboratories were classified as group C and 9 laboratories were classified as group D. Then the data under SR of 1 s-1 were analyzed to calculate the coefficient of variation (CV) in the group. Results There was significant difference among the WBV of blood samples measured by the viscometers B, C and D. The results under SR of 1 s-1 declined in turn, and they were highest under SR of 30 s-1 followed by the values of viscometer D and B and they were (8.14±0.75), highest under SR of 30 s-1 followed by the values of viscometer B and D, and they were (7.35±0.07), daily values of manufactory control and control A of each instruments in four groups were compared. Under SR of 1 s-1, there was no difference between daily values of manufactory control and control A in viscometer B (F = 2.63, 1.37, P > 0.05), and there was no difference of daily values of manufactory control among viscometer C and D (F = 0.33,3. 14, P > 0.05), but significant daily difference existed when control A was tested by viscometer C and D (F = 5.76, 8.00, P 0.05), and there was no difference of daily values of control A among 3 viscometers' (F = 1.03, 1.83, 2.40, P > 0.05); Under SR of 200 s-1, there was no difference of daily values of manufactory control among 3 viscometers (F =2.59, 0.68, 2.96, P > 0.05), and there was no difference of daily values of control A among 3 viscometers (F=2.31, 3.01, 2.28, P>0.05). When control A was tested under SR of 1 s-1 in 49 laboratories nationwide, the WBV values in groups of viscometer B, C and D were (18.47±1.30), (11.17±2.38), viscometer D and C were 63.75% and 21.3%. Conclusions Control A could fully mimic the properties of whole blood steadily on viscometer B, but partially mimic viscometer C and D, so the control A is most appropriate for viscometer B. Because current non-Newtonian fluid internal quality control could mimic rheological properties of whole blood under specifically conditions, laboratories should evaluate the consistent degree between control and whole blood, only the candidates which can mimic the properties of whole blood approximately could be chosen as quality control of WBV. When third-party control is chosen to be samples of EQA, its applicability should be in consideration. Pretest should be performed adequately to define applicability of third-party control, so as to reduce the difference among laboratories due to applicability of control and reflect detection quality of laboratories exactly. Key words: Measurement of whole blood viscosity; Applicability of control; Hemorheology

Prospective evaluation of pyrosequencing for the rapid detection of isoniazid and rifampin resistance in clinical Mycobacterium tuberculosis isolates

A pyrosequencing-based method for the rapid detection of isoniazid (INH) and rifampin (RIF) resistance in Mycobacterium tuberculosis was evaluated in clinical practice. The method can detect the INH resistance-causing katG315 mutation, and all mutations in the RIF resistance-determining rpoB core region, in less than 6 h from cultured isolates. The method was first validated with 42 isolates, and was subsequently prospectively evaluated with 91 isolates, including clinical isolates and external quality control assessment strains, over a period of 2.5 years. The pyrosequencing results of clinical isolates were available, on average, 19 days earlier (median 19 days; range 3-43 days) than conventional susceptibility testing results. The composite data showed that the sensitivity of pyrosequencing for detecting resistance correctly was 66.7% for INH and 97.4% for RIF. The specificity of pyrosequencing was 100% for both drugs. Acceptable sensitivity for detecting resistance and the rapidness of pyrosequencing make it a valuable tool in the clinical setting.

Current Status of Serum Allergen Tests in Korea

Due to the westernization of living environments in Korea, a number of allergy patients are greatly increasing. External quality control assessments are difficult for allergy tests due to the lack of reference methods. We surveyed the current status of allergy tests performed in medical laboratories in Korea to prepare for an external quality control assessment in the near future. We conducted a survey on internal and external quality control trials, calibrations and its intervals, medical staffs, analyzers in use, an average number of tests per months, and report formats. Among the 85 laboratories surveyed, 61 were doing allergy tests including 6 reference laboratories. There were two different types of analyzers (1) qualitative or semi-quantitative and (2) quantitative. These analyzers use either chemiluminescent or immunoblot method. Fifty-five laboratories were using 'qualitative or semi-quantitative' analyzers as a screening test and 31 laboratories were using quantitative analyzers. Most of the laboratories were only doing an internal quality control assessment included in the test kits. Excepting a few laboratories, calibrations were not done. About 34 laboratories reported numerical values with interpretative reports prepared by laboratory medical doctors. The necessity of external quality control assessment has become an issue for improving the quality of allergy tests. But due to the lack of standardization, it is difficult to carry out external quality control assessments. By grouping the laboratories in terms of the type of analyzers, we could overcome the problem of analyzer variations and launch an external quality control assessment program in the near future.

The clinical reality of guidelines for primary prevention of cardiovascular disease in type 2 diabetes in Italy

Introduction and aim Guidelines for cardiovascular prevention in diabetes have been issued by the national and international scientific societies. No audit as ever been performed to evaluate the implementation of these documents in clinical practice in Italy. The study evaluates the prevalence, treatment, and control of major cardiovascular risk factors in type 2 diabetic patients, to assess the clinical practice of primary cardiovascular prevention in type 2 diabetes. Patients and methods Two thousand four hundred and sixty-five men and women with type 2 diabetes, aged 50–75 and free of cardiovascular events were recruited on a consecutive basis at 10 hospital based outpatients diabetes clinics. Clinical variables were measured by standard protocol. Biochemical parameters were evaluated at each centre. The laboratories were monitored by an external quality control assessment in order to reach and maintain a standard of quality and traceability among the participating centres. Results A minority of patients (5%) met the recommended targets for LDL cholesterol, blood pressure, glycated haemoglobin and smoking habits, whereas the vast majority (66%) had unsatisfactory control of three or more of the above. Achievement of desirable control of risk factors differed according to gender and known diabetes duration. Lipid lowering and, to a lesser extent, antihypertensive medications were under-used and their titration insufficiently target-driven. Prophylactic use of antiplatelet agents was scarce, only one out of five patients was treated independent of absolute cardiovascular risk. Conclusion In clinical practice there is poor adherence to national and international guidelines for primary cardiovascular prevention in type 2 diabetes in Italy. The study underlines the great potential for prevention, particularly in women and in high-risk patients.

External quality control assessment in PCR diagnostics of dengue virus infections

Background: Increased travelling to countries endemic for dengue fever (DF) demands efficient laboratory diagnostics. Nucleic acid amplification techniques (NAT) are now frequently used for rapid diagnosis of imported viral diseases. Different PCR systems are available. Objectives: In order to assess the quality of molecular diagnostics of dengue virus infections, an external quality assurance (EQA) in PCR diagnostics was conducted. Study design: A panel of 10 human plasma samples was prepared and spiked with dengue virus types DEN-1 to DEN-4. In addition, a 10-fold dilution series (1:10–1:104 ) of DEN-3 virus was included. The panel was pre-tested by nested RT-PCR, in-house real-time PCR, and a commercial real-time PCR kit. The samples were inactivated by gamma irradiation and shipped in freeze dried state. Thirteen laboratories, within the European network for the diagnostics of imported viral diseases (ENIVD) took part using either single-round, nested, or real-time RT-PCR methods. Two laboratories used two methods in parallel, summarising up to 15 comparable results. Results: 33–100% correct results were achieved. All laboratories detected DEN-2 correctly, followed by DEN-1 (14 positive results of 15), DEN-3 (12/15) and DEN-4 (11/15). Testing of the serial dilution revealed low sensitivity in many labs, with results ranging from 33 to 80% of correctly tested samples. Conclusion: The EQA gives a feedback of the quality of the RT-PCR system used by each respective laboratory. The different test systems and amplification conditions demonstrate the importance of external quality control measures.

Preliminary External Quality Assessment for the Biological Monitoring of Carbon Disulfide with Urinary 2-Thiothiazolidine-4-Carboxylic Acid

Four laboratories have participated in an external quality control assessment for the determination of 2-thiothiazolidine-4-carboxylic acid (TTCA). TTCA is used as a biomarker for exposure to CS2. Thirteen different urine samples were analyzed by each laboratory. Ten of these were spiked with known amounts of TTCA, and had either a high or intermediate creatinine content. Two samples without any TTCA were used as controls and one sample was a pool of samples of urine from five employees occupationally exposed to CS2. The latter had unknown TTCA content. For each sample, TTCA and creatinine concentration were determined. The samples were supplied in three consecutive deliveries. Several samples were offered more than once. Thus, within-laboratory variability could be established for creatinine and TTCA determination and accuracy could be determined for TTCA analysis. Within-laboratory variability was low for all laboratories for creatinine, although laboratory D seemed to have a slight downward bias. Accuracy for TTCA was good for all laboratories. No significant mean deviation from the expected TTCA value was encountered. There does not seem to be any clear influence of the TTCA concentration level of the samples on the accuracy and within-laboratory variability. Two of the four laboratories (A and C) showed lower within-laboratory variability than the other two for TTCA, although coefficients of variation between replicated samples are high for these two laboratories as well. The laboratory giving the best accuracy, gave the highest within-laboratory variability. A non-systematic, random error is probably the source of this. The results of this preliminary study indicate that analysis of TTCA, although regarded as an established biomarker, can give biases and thus negatively interfere with inferred dose–effect or dose–response relationships in occupational epidemiology.

Preliminary External Quality Assessment for the Biological Monitoring of Carbon Disulfide with Urinary 2-Thiothiazolidine-4-Carboxylic Acid

Four laboratories have participated in an external quality control assessment for the determination of 2-thiothiazolidine-4-carboxylic acid (TTCA). TTCA is used as a biomarker for exposure to CS2. Thirteen different urine samples were analyzed by each laboratory. Ten of these were spiked with known amounts of TTCA, and had either a high or intermediate creatinine content. Two samples without any TTCA were used as controls and one sample was a pool of samples of urine from five employees occupationally exposed to CS2. The latter had unknown TTCA content. For each sample, TTCA and creatinine concentration were determined. The samples were supplied in three consecutive deliveries. Several samples were offered more than once. Thus, within-laboratory variability could be established for creatinine and TTCA determination and accuracy could be determined for TTCA analysis. Within-laboratory variability was low for all laboratories for creatinine, although laboratory D seemed to have a slight downward bias. Accuracy for TTCA was good for all laboratories. No significant mean deviation from the expected TTCA value was encountered. There does not seem to be any clear influence of the TTCA concentration level of the samples on the accuracy and within-laboratory variability. Two of the four laboratories (A and C) showed lower within-laboratory variability than the other two for TTCA, although coefficients of variation between replicated samples are high for these two laboratories as well. The laboratory giving the best accuracy, gave the highest within-laboratory variability. A non-systematic, random error is probably the source of this. The results of this preliminary study indicate that analysis of TTCA, although regarded as an established biomarker, can give biases and thus negatively interfere with inferred dose–effect or dose–response relationships in occupational epidemiology.

Determination of total selenium in serum, whole blood and erythrocytes by ICP-MS

A simple method for measuring selenium in serum by ICP-MS using a 1+14 dilution of a 100 µl sample in a diluent containing 1.0% v/v butan-1-ol to eliminate interferences at 78 Se from argon adduct ions has been shown to be accurate and precise in a 24 month evaluation for routine clinical assays and has been developed to allow analysis of whole blood and erythrocytes. Excellent performances were achieved in two External Quality Control Assessment programmes for the measurement of selenium in serum: Centre du Toxicologie de Quebec and Trace Element Quality Assessment Scheme from the University of Surrey (Guildford). The regression equation for our ICP-MS data versus target values for analysis of Se in 109 sera from November 1996 to March 1998 was: ICP-MS=0.969x Target+0.031 µmol l –l , r=0.996. For serum analysis the detection limit was 0.02 µmol l –1 , and the RSDs at 0.3-2.0 µmol l –1 were 2.0-4.0% within-run and 4.3-10.0% between-run. Initial applications of this method to measuring selenium in whole blood (1+14 dilution) and red blood cells (1+29 dilution) gave detection limits of 0.02 µmol l –1 ; RSDs of 2.1-5.8% within-run, and of 5.0-8.1% between-run, at concentrations of 0.3-2.0 µmol l –1 . Analysis of a whole blood reference sample (Seronorm 404107), with a target concentration of 1.01 µmol l –1 and acceptable range of 1.01-1.15 µmol l –1 , gave 1.06±0.06 µmol l –1 (mean±s).