Inter and Intra Laboratory Variation of Digoxin Radioimmunoassay in Sweden

Abstract

Samples from two pools were sent 10 times to 27 laboratories for assay ofdigoxin.One pool contained digoxin 2.60 nmol/l in normal plasma (SP); the other was pooled plasma from patients treated with digoxin (PP). Ten radioimmunoassay (RIA) methods were used. The mean of SP assays was 2.59 nmol/l, not significantly different from 2.60 nmol/l. The mean of PP determinations was 2.46 nmol/l. Within each of the 10 assay rounds, the concentrations showed an almost twofold variation and S.D. averaged 0.33 nmol/l and 0.31 nmol/l for SP and PP respectively.Significant differences (P<O.OOI) were found between mean concentrations obtained for the pools at various laboratories (SP range 2.15-2.85 nmolh; PP range 2.12-2.72 nmolh). The laboratory means obtained for SP and PP correlated significantly (P<O.OOl). Nevertheless, significant (:P<O.OI) variations between laboratories were found also concerning the mean difference between SP and PP concentrations. The interassay SD of the assays differed significantly between laboratories (range 0.05-0.61 nmol/l). Between and within groups of laboratories using the same RIA method and between various types of laboratories, differences were also found concerning both accuracy and precision of the assays. It is concluded that a better control of digoxin assay is needed.

Endogenous Cardiotonic Steroids: Physiology, Pharmacology, and Novel Therapeutic Targets

“…Most assays were based on cross-reactivity to the medication digoxin, and such cross-reactivity to other CTS varied dramatically (Sheiner et al, 1974; Bergdahl et al, 1979; Gruber et al, 1980; Bergdahl and Molin, 1981; Kelly, 1986; Pleasants et al, 1986). However, the most important inconsistency was that digitalis, the prototypical inhibitor of the Na + /K + -ATPase was not natriuretic in normal subjects (Hauptman and Kelly, 1999).…”

“…It is noteworthy that digoxin (200 μ g/kg/day) has been previously reported to reverse hypertension induced by chronic ouabain administration (Huang et al, 1999). Although the concept of endogenous digoxin as an antagonist of EO in humans is quite appealing, the extensive variability of commercial digoxin immunoassays to detect endogenous CTS (Sheiner et al, 1974; Bergdahl et al, 1979; Bergdahl and Molin, 1981; Kelly, 1986; Goto et al, 1991a, 1992) argues strongly against this possibility.…”

The Trade-Off between Dietary Salt and Cardiovascular Disease; A Role for Na/K-ATPase Signaling?

“…In particular, prevailing CTS assays were based on cross-reactivity of CTS with antibodies to digoxin. This cross-reactivity of the commercially employed anti-digoxin antibodies to CTS varied considerably (27–32). Probably, the most important inconsistency was that digitalis did not appear to be natriuretic in normal subjects (33).…”