We review our experience with the development, validation, and long-te
rm operation of suppression-based ion chromatography reference methods
for clinically important serum cations. First, we describe the accura
cy and precision requirements for reference methods in clinical chemis
try, Then, we present the general design of our methods and their vali
dation with certified reference materials and method comparison with f
lame atomic emission and flame atomic absorption spectrometry. Additio
nally, we compare basic features of commercially available standard io
n chromatography systems for our applications. Further, we discuss the
influence of different sample preparation methods on accuracy and rob
ustness of the methods. Among others, we describe reversed-phase clean
-up and removal of anions with minicolumns or chromatographic front-cu
t with column-switching. Applications of the methods are presented for
the field of external quality assessment and evaluation of accuracy a
nd specificity of routine methods. (C) 1997 Elsevier Science B.V.