Frozen Human Serum Reference Material for Standardization of Sodium and Potassium Measurements in Serum or Plasma by Ion-Selective Electrode Analyzers

Abstract

Three interlaboratory round-robin studies (RR1, RR2, and RR3) were conducted to identify a serum-based reference material that would aid in the standardization of direct ion-selective electrode (ISE) measurements of sodium and potassium. Ultrafiltered frozen serum reference materials requiring no reconstitution reduced between-laboratory variability (the largest source of imprecision) more than did other reference materials. ISE values for RR3 were normalized by the use of two points at the extremes of the clinical range for sodium (i.e., 120 and 160 mmol/L), with values assigned by the flame atomic emission spectrometry (FAES) Reference Method. This FAES normalization of ISE raw values remarkably improved all sources of variability and unified the results from seven different direct ISE analyzers to the FAES Reference Method value. Subsequently, a three-tiered, fresh-frozen human serum reference material was produced to the specifications developed in RR1-RR3, was assigned certified values for sodium and potassium by Definitive Methods at the National Institute of Standards and Technology (NIST), and was made available in 1990 to the clinical laboratory community as a Standard Reference Material (SRM); it is now identified as SRM 956. Albeit retrospectively, we show how applying an FAES normalization step identical to that used in RR4/5 to the ISE data for SRM 956 after the NIST Definitive Method values were known, consistently moved the ISE results for RR3 closer to the true value for Na+ and K+.

Intermethod Variability of Sodium and Potassium Results: Patients Sera and Commercially Available Control Sera

“…The observed bias may be corrected for by recalibration with materials having values assigned by flame photometry (1). For such a procedure to be effective, however, the materials must show an interassay behaviour similar to that of patient sera, i. e. they have to be commutable.…”

“…Methods based on "indirect" potentiometry (diluted sample), with ion-selective electrodes, are widely used for the clinical measurement of sodium and potassium in serum. Alternative analytical approaches include "direct" potentiometry (undiluted sample), also widely used (1), and enzyme activation-based photometric methods (2,3). Flame atomic emission photometry is mainly used for reference purposes (4).…”

“…The very low intra-individual biological variation of serum sodium and potassium (5) requires accurate measurements (6,8). On the other hand, methods based on different principles may be expected to give different results, more so if the different methods respond to different, although related, quantities, either substance concentration or ion activity (1). It has been suggested that method-dependent results be equalized by making them consistently traceable to flame photometry, by means of adequate calibration processes, in spite of different analytical principles and different quantities measured (1).…”

“…The term "commutability" was first suggested to refer to "the ability of an enzyme material to show inter-assay changes comparable to those of patient sera " and it was later extended to non-enzymic components in control sera (9). Many commercially available control sera have been shown to lack such a property (10,11), and freshfrozen human serum proved to be the best material for transferring the trueness from reference to ion-selective electrode measurements of sodium and potassium (1).…”

Certification of Ca, Mg, and K in human plasma reference material using isotope dilution inductively coupled plasma mass spectrometry

“…7,8 To meet such a requirement, National Metrology Institutes (NMIs) worldwide have developed certified reference materials (CRMs) for the analysis of various analytes of clinical importance. [9][10][11][12][13][14] In the case of clinical samples, such as serum and plasma, often composed of almost identical matrices due to homeostatic regulatory mechanisms operational in physiological processes, matrix-matched CRMs can be made available and provide an efficient means for quality control and method validation in clinical analysis.…”