The results of implementation of different clinical laboratory techniques are to be equal in clinically significant limits to be optimally applied in diagnostics of diseases and treatment of patients. When the results of laboratory tests are not standardized and harmonized for the very same clinical assay the results can be expressed by unmatched numbers. Unfortunately, in some handbooks the values are presented based on the results of application of specific laboratory techniques without considering possibility or likelihood of differences between various techniques. When this is a case, accumulation of data of diferent clinical research studies and working out of clinical handbooks on this basis will be inconsistent. Inadequate understanding of issue that the results of laboratory tests are not standardized and harmonized can lead to incorrect clinical, financial, managerial or technical decisions. The standardization of clinical laboratory techniques was applied to many measurands related to primary referent techniques (standard specimen of pure substance) or/and developed referent measurement techniques. However, harmonization of clinical laboratory techniques for those measurands which are not related any developed measurement techniques is quite problematic due to inadequate determination of measurand, its inadequate analytical specificity, insufficient attention to commutability of referent materials and poor systematic approach to harmonization. To overcome these issues an infrastructure is to be developed to support systematic approach to identification and prioritization of measurands which are to be harmonized on the basis of clinical importance and technical applicability. The management of technical implementation harmonization process for specific measurands.

(O) under bar(b) under bar(j) under bar(e) under bar(c) under bar(t) under bar(i) under bar(v) under bar(e) under bar: The aim of this Study was to investigate serum Ionized magnesium (i-Mg) levels in patients with various stages of renal failure and to compare them with serum total magnesium (t-Mg). (M) under bar(e) under bar(t) under bar(h) under bar(o) under bar(d) under bar(s) under bar (a) under bar(n) under bar(d) under bar (m) under bar(e) under bar(t) under bar(h) under bar(o) under bar(d) under bar(s) under bar: We Studied 69 nondiabetic ambulatory patients not receiving diuretics, polystyrene sulfonate or NaHCO3. Serum i-Mg was measured with an ion-selective electrode and serum t-Mg by ion chromatography. Renal function was determined by the creatinine clearance (C-Cr), applying the normalized Cockcroft-Gault formula. (R) under bar(e) under bar(s) under bar(u) under bar(l) under bar(t) under bar(s) under bar: Overall, i-Mg, as well as t-Mg, showed a statistically significant negative logarithmic correlation with C-Cr (i-Mg: r = -0.75; t-Mg: r = -0.73) and i-Mg highly correlated with t-Mg (r = 0.94). Surprisingly, in mild renal failure (C-Cr > 80 ml/min/1.73 m(2)), i-Mg and t-Mg were in the low-normal to hypomagnesemic range (i-Mg <= 0.56 mmol/l, t-Mg: 0.85 mmol/l). In moderate renal failure (C-Cr < 30 and <= 80 ml/min/1.73 m(2)), I-Mg and t-Mg were usually in the reference interval (i-Mg: 0.49 - 0.63 mmol/l, t-Mg: 0.75 - 0.95 mmol/l). In severe renal failure (C-Cr < 30 ml/min/1.73 m(2)), i-Mg and t-Mg were in the high-normal to hypermagnesemic range (i-Mg >= 0.56 mmol/l, t-Mg >= 0.85 mmol/l). (C) under bar(o) under bar(n) under bar(c) under bar(l) under bar(u) under bar(s) under bar(i) under bar(o) under bar(n) under bar(s ) under bar: The measurement of i-Mg offered no advantage over the measurement of t-Mg. The observation of low Mg values in mild renal failure may have implications for the common treatment of chronic renal failure (CRF) patients with drugs that have a Mg-lowering side effect (diuretics, potassium-lowering agents).

Context.-In proficiency testing surveys, there are differences in the values reported by users of various analytic methods. Two contributors to this variation are calibrator bias and matrix effects of proficiency testing materials.Objectives.-(1) To quantify the biases of the analytic methods used to measure thyroid-stimulating hormone, thyroxine, triiodothyronine, free thyroxine, and free triiodothyronine levels; (2) to determine if these biases are within allowable limits; and (3) to ascertain if proficiency testing materials correctly identify these biases.Design.-A fresh frozen serum specimen was mailed as part of the 2003 College of American Pathologists Ligand and Chemistry surveys. The means and SDs for each analytic method were determined for this sample as well as for a proficiency testing sample from both surveys. In the fresh frozen serum sample, target values for thyroxine and triiodothyronine were determined by isotope dilution/liquid chromatography/tandem mass spectrometry. All other target values in the study were the median of the means obtained for the various analytic methods.Main Outcome Measures.-Calibration biases were calculated by comparing the mean of each analytic method with the appropriate target values. These biases were evaluated against limits based on intra- and interindividual biological variation. Matrix effects of proficiency testing materials were assessed by comparing the rank of highest to lowest analytic method means (Spearman rank test) for each analyte.Participants.-Approximately 3900 clinical laboratories were enrolled in the College of American Pathologists Chemistry and Ligand surveys.Results.-The number of methods in the Ligand Survey that failed to meet the goals for bias was 7 of 17 for thyroid-stimulating hormone and 11 of 13 for free thyroxine. The failure rates were 12 of 16 methods for thyroxine, 8 of 11 for triiodothyronine, and 9 of 11 for free triiodothyronine. The means of the analytic method for the proficiency testing material correlated significantly (P < .05) only with the fresh frozen serum means for thyroxine and thyroid-stimulating hormone in the Chemistry Survey and free triiodothyronine in the Ligand Survey.Conclusions.-A majority of the methods used in thyroid function testing have biases that limit their clinical utility. Traditional proficiency testing materials do not adequately reflect these biases.

CONTEXT:The National Kidney Disease Education Program recommends calculating glomerular filtration rate from serum creatinine concentration. Accurate creatinine measurements are necessary for this calculation.OBJECTIVE:To evaluate the state of the art in measuring serum creatinine, as well as the ability of a proficiency testing program to measure bias for individual laboratories and method peer groups.DESIGN:A fresh-frozen, off-the-clot pooled serum specimen plus 4 conventional specimens were sent to participants in the College of American Pathologists Chemistry Survey for assay of creatinine. Creatinine concentrations were assigned by isotope dilution mass spectrometry reference measurement procedures.PARTICIPANTS:Clinical laboratories with an acceptable result for all 5 survey specimens (n = 5624).RESULTS:The fresh frozen serum (FFS) specimen had a creatinine concentration of 0.902 mg/dL (79.7 micromol/L). Mean bias for 50 instrument-method peer groups varied from -0.06 to 0.31 mg/dL (-5.3 to 27.4 micromol/L), with 30 (60%) of 50 peer groups having significant bias (P < .001). The bias variability was related to instrument manufacturer (P < or = .001) rather than method type (P = .02) with 24 (63%) of 38 alkaline picric acid methods and with 6 (50%) of 12 enzymatic methods having significant biases. Two conventional specimens had creatinine concentrations of 0.795 and 2.205 mg/dL (70.3 and 194.9 micromol/L) and had apparent survey biases significantly different (P < .001) from that of the FFS specimen for 34 (68%) and 35 (70%) of 50 peer groups, respectively.CONCLUSIONS:Thirty of 50 peer groups had significant bias for creatinine. Bias was primarily associated with instrument manufacturer, not with type of method used. Proficiency testing using a commutable specimen measured participant bias versus a reference measurement procedure and provided trueness surveillance of instrument-method peer groups.

This manuscript explains the establishment and validation of metrological traceability of calibration for routine measurement procedures using common medical decisionmaking criteria. Metrological traceability is considered the basis for achieving comparability of measurement results in laboratory medicine. This concept is supported by European legislation, which demands that manufacturers provide assurance and demonstrate metrological traceability of in vitro Diagnostic Medical Devices. The guidance to comply with these legislative requirements is available in different CEN/ISO standards and is used as a basis of this manuscript. The goals and accomplishments in metrological traceability of SI and nonSI analytes is considered. Specific problems, such as nonavailability of primary reference materials and measurement procedures, lack of official endorsement, and noncommutability of certain reference materials are discussed. With respect to noncommutability, the use of splitsample measurements is advocated. Also, the expression of measurement uncertainty associated with the application of the metrological traceability chain is discussed. In addition, the need for postmarket vigilance assessment of traceable performance is considered. Finally, laboratory medicine scientific and professional societies, diagnostics manufacturers, and clinicians are urged to share responsibilities for understanding the implications of metrological traceability of routine measurements.

The difference, or Bland–Altman plot (1)(2)(3)(4) has become a popular tool for the presentation of method-comparison studies (5)(6), but the plot has rarely been used for making decisions about the quality of a method (5)(6). Bland and Altman expressed this in the terms “we want to know by how much the new method is likely to differ from the old; if this is not enough to cause problems in clinical interpretation we can replace the old method by the new or use the two interchangeably. How far apart measurements can be without causing difficulties will be a question of judgment. Ideally, it should be defined in advance to help in the interpretation of the method comparison and to choose the sample size” (2). The tool for doing so was to investigate whether the upper (UCL) or lower (LCL) 95% confidence limit of 1.96 SD of the differences between the methods (UCL1.96 SD,diff, LCL1.96 SD,diff) was equal to or smaller than a predefined limit for total error (TE; acceptance, UCL1.96 …

The accurate antenatal prediction of fetal lung maturity (FLM) based on results from amniotic fluid samples is of

An external quality assessment (EQA) survey on 14 fresh‐frozen, single‐donation sera assigned with reference measurement procedure (RMP) values revealed a mean bias of +5.2% and +3.7% for the cholesterol oxidase and the photometric glucose oxidase procedure groups, respectively. Conversely, on lyophilized sera, the same procedure groups showed almost bias‐free results, the differences from the RMP values being only −0.8% for cholesterol and +0.7% for glucose. These data, which are in fairly good agreement with the literature, suggest the existence of artificial matrix effects in processed materials. Therefore they indicate that, currently, assessment of trueness is hampered in many European EQA schemes, as most of them use lyophilized sera. This approach may give a false impression about the trueness of laboratory results as well as carrying the risk that laboratories calibrated on the RMP values of the survey samples could make errors in patient testing. Consequently, if European EQA is willing to fulfil a post‐market vigilance function of the performance of in vitro diagnostic medical devices, then the time has come to tackle the problem of the quality of the survey samples. EQA organizers urgently need to make an effort to seek out materials that analytically behave like authentic clinical specimens. In the meantime, alternative approaches should be used. Although not ideal, the special survey described in this article is one of the possibilities. Naturally, it implies logistic problems and increased costs for the individual EQA schemes. However, both can be overcome with the cooperation of the predominantly nationally organized schemes.

Standardisation du dosage d'hémoglobine glyquée dans le sang. Le manuscrit présenté aborde la standardisation du dosage d'hémoglobine glyquée dans le sang. La première démarche, initiée aux États-Unis, était basée sur un consensus. Elle reposait sur un ajustement des méthodes de routine par rapport à une méthode de comparaison, notamment une méthode par chromatographie liquide haute performance. L'ajustement supposait l'usage de calibrateurs communs et une comparaison de méthodes à base d'échantillons natifs, tous portant des valeurs d'HbA1c attribuées par la méthode désignée. Malgré la réalisation d'un accord de résultats raisonnable, la démarche pragmatique a perdu du terrain en faveur de la notion de standardisation proposée par l'IFCC, c'est-à-dire, par rapport à un système de référence. Ce système comprend un accord sur le constituant à doser, notamment l'HbA1c, des préparations de référence d'HbA1c et HbA0 et une (des) méthode(s) de référence. Il est clair que les caractéristiques inhérentes à ce système de référence supposent des implications importantes lors de son établissement dans la pratique clinique. Entre autres, un abaissement des valeurs d'HbA1c est prévu. C'est dans cette perspective que la démarche de l'IFCC surpassera la standardisation purement technique. Elle prévoit notamment aussi bien des mesures pour maintenir l'expérience clinique dans le contrôle et la thérapie de la maladie diabétique.

Rapid Communications in Mass SpectrometryVolume 14, Issue 10 p. 936-937 Letter to the Editor Matrix effect in the quantitative analysis of urinary C-peptide by liquid chromatography/mass spectrometry Colette Fierens, Colette Fierens Laboratorium voor Analytische Chemie en Klinishe Analyse, Faculteit Farmaceutische Wetenschappen, Universiteit Gent, Harelbekestraat 72, 9000 Gent, BelgiumSearch for more papers by this authorLinda M. Thienpont, Linda M. Thienpont Laboratorium voor Analytische Chemie en Klinishe Analyse, Faculteit Farmaceutische Wetenschappen, Universiteit Gent, Harelbekestraat 72, 9000 Gent, BelgiumSearch for more papers by this authorDietmar Stöckl, Dietmar Stöckl Laboratorium voor Analytische Chemie en Klinishe Analyse, Faculteit Farmaceutische Wetenschappen, Universiteit Gent, Harelbekestraat 72, 9000 Gent, BelgiumSearch for more papers by this authorAndré P. De Leenheer, Corresponding Author André P. De Leenheer Laboratoria voor Medische Biochemie en Klinishe Analyse, Faculteit Farmaceutische Wetenschappen, Universiteit Gent, Harelbekestraat 72, 9000 Gent, BelgiumLaboratoria voor Medische Biochemie en Klinische Analyse, Facultlit Farmaceutische Wetenschappen, Universiteit Gent, Harelbekestraat 72, 9000 Gent, BelgiumSearch for more papers by this author Colette Fierens, Colette Fierens Laboratorium voor Analytische Chemie en Klinishe Analyse, Faculteit Farmaceutische Wetenschappen, Universiteit Gent, Harelbekestraat 72, 9000 Gent, BelgiumSearch for more papers by this authorLinda M. Thienpont, Linda M. Thienpont Laboratorium voor Analytische Chemie en Klinishe Analyse, Faculteit Farmaceutische Wetenschappen, Universiteit Gent, Harelbekestraat 72, 9000 Gent, BelgiumSearch for more papers by this authorDietmar Stöckl, Dietmar Stöckl Laboratorium voor Analytische Chemie en Klinishe Analyse, Faculteit Farmaceutische Wetenschappen, Universiteit Gent, Harelbekestraat 72, 9000 Gent, BelgiumSearch for more papers by this authorAndré P. De Leenheer, Corresponding Author André P. De Leenheer Laboratoria voor Medische Biochemie en Klinishe Analyse, Faculteit Farmaceutische Wetenschappen, Universiteit Gent, Harelbekestraat 72, 9000 Gent, BelgiumLaboratoria voor Medische Biochemie en Klinische Analyse, Facultlit Farmaceutische Wetenschappen, Universiteit Gent, Harelbekestraat 72, 9000 Gent, BelgiumSearch for more papers by this author First published: 22 May 2000 https://doi.org/10.1002/(SICI)1097-0231(20000530)14:10<936::AID-RCM960>3.0.CO;2-ACitations: 8Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinkedInRedditWechat No abstract is available for this article. REFERENCES 1Ikonomou MG, Blades AT, Kebarle P. Anal. Chem. 1990; 62: 957. 2Kebarle P, Tang L. Anal. Chem. 1993; 65: 972A. 3Matuszewski BK, Constanzer ML, Chavez-Eng CM. Anal. Chem. 1998; 70: 882. 4Fu I, Woolf EJ, Matuszewski BK. J. Pharm. Biomed. Anal. 1998; 18: 347. 5Pollettini A, Marrubini-Bouland G, Montagna M. J. Chromatogr. B 1998; 713: 339. Citing Literature Volume14, Issue1030 May 2000Pages 936-937 ReferencesRelatedInformation

Measurement of glycohemoglobin (GHb) in blood is of central importance in the management of the diabetic patient. The Diabetes Control and Complication Trial has confirmed that good control of the glycemic state substantially reduces the development and progress of associated late complications (1)(2). Because tests for the measurement of blood GHb often give different results, the IFCC established a Working Group on Glycohemoglobin Standardization (3). The Working Group defined the analyte “glycohemoglobin” as the stable adduct of glucose to the N-terminal valine of the β-chain of hemoglobin, i.e., N -(1-deoxyfructosyl)hemoglobin, or HbA1c (3), and developed candidate primary reference materials [mixtures of purified HbA1c and non-glycohemoglobin A (HbA)] and two reference methods (4)(5). One reference method is based on liquid chromatography-electrospray ionization-mass spectrometry (LC-ESI-MS) of the β-N-terminal hexapeptides of HbA1c and HbA obtained by enzymatic cleavage of the intact hemoglobin (Hb) molecule with endoproteinase Glu-C (5). The method has been demonstrated as reliable in intercomparison studies (6), but it has a relatively long analysis time (total cycle time of the HPLC program is 24 min). The LC part of the method utilizes a 150 × 2.1 mm Zorbax® SB-CN column (5 μm bead size; 80 A pore size) in the reversed-phase mode with a water-acetonitrile gradient (both containing ∼0.23 mL/L trifluoroacetic acid). For ESI-MS detection, it makes use of the single-ion recording (SIR) mode of the [M+2H]+ ions at m / …

Because of a printer error, the Table⇓ that should have appeared with the Letter by Dewitte et al. in the January issue of this Journal ( Clinical Chemistry 1999;45:157–8) was printed on the wrong page. Following is the Letter with the Table⇓ included. The printer apologizes for any confusion this may have caused. View this table: Table 1. UF-cMg2+ expressed as fraction (in % ±SD) of S-cMg2+ at different pH values. Measurements of ionized magnesium (Mg2+) in serum and ultrafiltrate (S-cMg2+ and UF-cMg2+) are expected to give identical results, provided that (a) ultrafiltration does not disturb the equilibrium of S-cMg2+; (b) the complexation behavior of Mg2+ is identical in both matrices; and (c) matrix effects in sensing Mg2+ therein are absent. In a recent article in this Journal, however, Zoppi and Cristalli (1), referring to data of a prior study (2), reported an unexpectedly low value for UF-cMg2+ (Table 1⇑ ). Because of an increase of the pH in the ultrafiltrate to 8.3 attributed to the loss of dissolved CO2 and the absence of proteins, they recalculated S-cMg2+ to a pH of 8.3. Because this correction could not fully compensate for the difference (Table 1⇑ ), they also corrected S-cMg2+ with a bicarbonate factor. With these changes, UF-cMg2+ was 10% higher than the overall corrected S-cMg2+. In our opinion, the approach raises several questions. Zoppi and Cristalli (1) corrected only S-cMg2+ for bicarbonate, and moreover, they used a factor that was derived from aqueous solutions at the actual pH (2). If used at all, such a correction should be based on the difference of the bicarbonate effect in …