Summary: In the Federal Republic of Germany there are guidelines for a basic program for internal and external quality control of quantitative clinical chemical analyses prepared by the German medical society in connection with the Calibration Act. These guidelines specify that for internal accuracy control and for interlaboratory surveys, control specimens are to be used with assigned values and assigned intervals that have been determined by partic-ularly well-qualified, independent laboratories serving as reference laboratories. The assigned values are often different from the best estimate (by measurement) of the "true value. " They are influenced by the matrix of the specimen and by the method used, and they must be determined under routine conditions. The protocol for obtaining the analytical results under carefully defined conditions is described in detail. The statisti-cal treatment of the analytical results and the authors ' observations on the structure of the data and the properties of the dispersion and location parameters for the individual laboratories are discussed. These observations led to the development of a procedure for selecting assigned intervals and assigned values in which no special assumptions are made about how the data are distributed. This procedure is described in detail. The importance of the authors ' observations for the evaluation of analytical results in the clinical laboratory and for the statistical treatment of such data is discussed. Comparative studies were carried out using the same control specimens with other designs for assigned value deter-

a feasibility study of a split-sample comparison for that purpose. Processed, frozen single-donation sera as-signed target values by candidate reference measure-ment procedures (cRMPs) were used with immunoas-says for total thyroxine (TT4) and triiodothyronine (TT3) as models. Methods: Two serum panels were quantified for TT4 and TT3 with validated cRMPs and measured in parallel with at least 14 immunoassays. The results were inter-preted in terms of traceability of calibration (trueness) and of the individual measurement result (accuracy) by linear regression analysis and graphical representation against specifications. The commutability of the sera was investigated by parallel analysis of TT4 in freshly collected but nonfiltered specimens. Results: The TT4 (TT3) concentrations in the sera (ac-cording to the cRMPs) were 64–269 nmol/L (0.88–13.7 nmol/L). The method comparison showed that for TT4, on average, the immunoassays produced results in agreement with the cRMPs, whereas for TT3, results were typically higher. It also demonstrated a consider-able between-assay divergence in traceability of calibra-tion and accuracy. The evidence of noncommutability of the sera attributable to processing, however, indicates that the interpretation should be treated with caution. Conclusions: Frozen sera can be used for documenting/ validating traceability of total thyroid measurements. The way in which the sera are processed may jeopardize commutability, however, and therefore requires in-depth investigation. © 2005 American Association for Clinical Chemistry Trueness-based harmonization of measurement results among laboratories and measurement procedures is a longstanding objective of laboratory medicine [see, for example, Refs. (1–4)]. In spite of ambitious standardiza-tion projects by authoritative organizations such as the

Summary: Separation and determination of sample constituents by capillary isotachophoresis are entirely based on physical phenomena. The method has therefore been proposed as a universal reference method for ionic constituents. The present paper shows that even neutral species can be adequately determined after suitable preceding reactions. Urea was completely hydrolysed by urease (EC 3.5.1.5) to ammonia and bicarbonate, followed by direct measurement of the ammonium ion concentration by capillary isotachopho-resis. Standard Reference Material No. 912a urea (National Bureau of Standards) was used as a primary standard. The analytical linear range of the method extends to 64 mmol urea per litre. The precision of the method was in the range of 1.05 — 2.64 % (CV) and the analytical recovery of added urea was excellent (99.4%, SD 1.13%). Further proof of accuracy was obtained by analysing the NBS human reference serum (standard reference material 909). The mean result by the capillary isotachophoretic method, 9.52 ± 0.085 mmol/1, agrees well with the reference value, 9.64 mmol/1. The results obtained by capillary isotachophoresis showed good agreement with those obtained by the coupled-enzyme method (r = 0.995).

The concentration of albumin in intravascular fluid represents the balance between the com-plex and inter-dependent processes of syn-thesis, secretion and degradation I, 2 and in the adult is normally maintained at about 40 glL.3 Albumin is a single peptide chain of over 580 amino-acid residues, with a molecular weight of about 66 000 Daltons. 4 The heterogeneity of serum albumin is now well known " although it is only recently that the clinical and laboratory implications of variant albumins have begun to be recognised. Familial dysalbuminaemic hyperthyroxinaemia was de-scribed in 19816 and subsequent studies have confirmed the presence of an albumin with an abnormal binding site with a high affinity for thyroxine in such subjects. " Re.cent studi~s suggest that the albumin variant IS present m small amounts in normal blood. H The labora-tory finding of bisalbuminaemia is usually without clinical consequences; however, some albumin variants may interfere with the measurement of albumin. Two allo-albumins have been reported to show decreased bindi~g with the dye 2-(4 '-hydroxybenzeneazo) benzoic acid (HABA dyet III and more recently an albumin has been described in three genera-tions of a family that shows increased bindi~g with bromocresol green (BCG). Heterogeneity could not be detected by cellulose acetate electrophoresis but the abnormal component separated from normal albumin during column chromatography with DEAE-Sepharose. l \ Albumin is the most abundant plasma pro-tein and the causes of hypoalbuminaemia are well known and described in current textbooks of clinical chemistry. However, the clinical indications for the measurement of albumin in This publication was prepared at the invitation. of ~~e

a feasibility study of a split-sample comparison for that purpose. Processed, frozen single-donation sera, as-signed target values by candidate reference measure-ment procedures (cRMPs), were used with immunoas-says for total thyroxine (TT4) and triiodothyronine (TT3) as models. Methods: Two serum panels were quantified for TT4 and TT3 with validated cRMPs and measured in parallel with at least 14 immunoassays. The results were inter-preted in terms of traceability of calibration (trueness) and of the individual measurement result (accuracy) by linear regression analysis and graphical representation against specifications. The commutability of the sera was investigated by parallel analysis of TT4 in freshly collected but nonfiltered specimens. Results: The TT4 (TT3) concentrations in the sera (ac-cording to the cRMPs) were 64–269 nmol/L (0.88–13.7 nmol/L). The method comparison showed that for TT4, on average, the immunoassays produced results in agreement with the cRMPs, whereas for TT3, results were typically higher. It also demonstrated a consider-able between-assay divergence in traceability of calibra-tion and accuracy. The evidence of noncommutability of the sera attributable to processing, however, indicates that the interpretation should be treated with caution. Conclusions: Frozen sera can be used for documenting/ validating traceability of total thyroid measurements. The way in which the sera are processed may jeopardize commutability, however, and therefore requires in-depth investigation. © 2005 American Association for Clinical Chemistry Trueness-based harmonization of measurement results among laboratories and measurement procedures is a longstanding objective of laboratory medicine [see, for example, Refs. (1–4)]. In spite of ambitious standardiza-tion projects by authoritative organizations such as the

Determination of total cholesterol in serum by liquid chromatography–isotope dilution mass spectrometry Ruediger Kock, * Bert Delvoux, and Helmut Greiling We have developed a liquid chromatography–isotope dilution mass spectrometry procedure to quantify total cholesterol in serum. A particle-beam interface was used for coupling the liquid chromatograph and the mass spectrometer. After electron impact ionization the ions m/z 5 386 and m/z 5 389 were used for selective ion monitoring of cholesterol and the internal standard [25,26,27-13C]cholesterol. The sample preparation steps required for serum materials are alkaline hydrolysis and an extraction of the cholesterol into the cyclohexane phase. Imprecision for the determination of cholesterol