Talanta, Vol. 31, No. lOB, pp. 851-862, 1984 Printed in Great Britain. All rights reserved 0039-9140/84 $3.00 + 0.00 Copyright © 1984 Pergamon Press Ltd QUALITY CONTROL IN CLINICAL CHEMISTRY: CHARACTERIZATION OF REFERENCE MATERIALS ROBERT REJ and RICHARD W. JENNY Wadsworth Center for Laboratories and Research, New York State Department of Health, Albany, NY 12201, U.S.A. JEAN-PIERRE BRETAUDIERE Department of Pathology and Laboratory Medicine, The University of Texas Medical School, Houston, TX 77025, U.S.A. (Received 24 May 1984. Accepted 12 June 1984) Summary-Reference serum preparations are key components of internal and external quality-control programmes. These materials are often poorly characterized, and use of inappropriate specimens may result in erroneous conclusions regarding quality of laboratory data. Several techniques are described that characterize specimens used in the quality-control or calibration of laboratory procedures. A characteristic approach requires detailed study of a few fundamental characteristics of reference preparations-such as steady-state kinetic properties of an enzyme-and comparison with the same parameters determined for patient specimens. Descriptive techniques-ratio methods and the multivariate statistical procedure of correspondence analysis-are used for further description of the interactions of materials in a variety of assay methods. The applications of these procedures to two clinical analytes-theophylline and alkaline phosphatase-are described. The fundamental objective of statistical quality- control programmes in the clinical laboratory is to characterize the analytical process accurately and thereby provide information regarding the quality of results reported for clinical specimens. This in- formation may be used for a number of purposes. An internal quality-control programme may provide information about the routine performance of an analytical technique-and thereby serve as a basis for selection of one among many procedures available-or give on-line monitoring of an ana- lytical process in which acceptance of a result de- pends on whether it falls within predetermined limits. External quality-control provides a basis for indepen- dent characterization of laboratory performance and gives information on the reliability of test procedures in various locations and in laboratories with different backgrounds. External quality-control programmes serve, in some instances, for the determination of acceptability, licensing, or eligibility for reim- bursement for laboratory services. The reliability of this assessment of quality is dependent on a variety of factors, but the key to the success of all these schemes is that the reference materials used simulate as closely as possible the clinical specimens analysed. This facet of quality control is often (incorrectly) assumed or (equally erroneously) overlooked in both internal and external quality-control programmes. The scope of this paper is the review of criteria for materials used in clinical laboratory quality-control programmes and to pro- Portions of the introductory material in this paper were included in a paper in Clin. Chem., 1981, 27, 798 and are adapted here with permission. 851 vide a basis on which their acceptibility can be judged. Various types of reference materials are currently used in quality control programmes, ,_ 9 and differ in their basic composition and physical character. Specimens may be prepared from human serum, plasma that has been "converted" into a serum- like state, various animal sera, albumin solutions, or synthetic substances, and are distributed in the dry or liquid state. Because stability is a prime requirement for such specimens, most are in lyophi- lized form. Unfortunately, freeze-drying alters certain physicochemical properties of biological materi- als; 10 - 12 for example, human lipoproteins are irre- versibly denatured, and consequently serum viscosity may be changed, serum turbidity increased, 13 • 14 and the spectral properties altered. 15 Removal of lipo- proteins prior to lyophilization, 14 • 16 or addition of sucrose 17 in order to minimize specimen turbidity, also results in materials that are fundamentally altered. Other typical treatments of quality-control sera include dialysis and addition of matrix expan- ders, preservatives, antimicrobial agents, surfactants, and clarifying agents. 18 - 20 Concentrations of constituents are also often altered by attempts to obtain reference specimens with analyte concentrations outside the "normal" ranges. Such specimens, usually prepared by dilution or by addition of pure materials to a normal speci- men, may differ from the sample sera because metab- olites or other substances are lacking. Therefore, in use of a non-specific method that is influenced by one or several metabolites, the results for such a supple- mented quality-control material will not be affected in the same way as those for a patient's serum. Such