Analyte Stability in Clinical Chemistry Quality Control Materials

Abstract

We have reviewed literature reporting stability characteristics of a wide variety of analytes in lyophilized, liquid, and frozen matrices used for control purposes. The most commonly reported unstable analytes in unreconstituted lyophilized controls are glucose, CPK., and SGPT (ALT). Occasional reports indicate instability in a variety of other analytes. Increasing alkaline phosphatase activity and decreasing CPK activity are commonly noted in reconstituted lyophilized materials. The definition of stability must take into consideration the analytic method employed and refers to a measured change in concentration of analytes by the given method. The wide variety of statistical approaches used to assess stability have been reviewed. Techniques employing multiple measurements over time and using parametric statistics are desirable, but alternate methods have provided useful information and may also be employed depending on the nature of the data base and the frequency of timed measurements. These measurements have been obtained in individual laboratories, small groups of laboratories, or large groups of laboratories participating in interlaboratory programs such as Surveys or Regional Quality Control Programs. Unstable controls affect statistical schemes used to interpret acceptability of analytic runs, contributing to analytic inefficiency by increasing the frequency of warning and action error signals. Unstable calibration reference materials cause bias in the measuring system. The degree of demonstrable instability in control products used for calibration purposes has not been sufficiently widespread or large to effect substantially analytic results over the short term. There is potential for bias approaching levels of allowable error according to medical usefulness criteria if unstable calibration material goes undetected over a long period of time, e.g., 1 year. No definition of allowable instability, either analytic or medical, has been formulated, nor can one be given at this time based on available information. In any case, definitions should consider, in a chemical sense, the precision with which an analyte is customarily measured and degree of analytic inefficiency caused by unstable controls, and in a medical sense, medical usefulness criteria.