Determination of reference method values by isotope dilution-gas chromatography/mass spectrometry: a five years' experience of two European Reference Laboratories.

We report on the cooperation of two European Reference Laboratories for the determination of reference method values in serum based materials intended for use in internal accuracy control and external quality assessment. Reference method values were determined by isotope dilution-gas chromatography/mass spectrometry for aldosterone, cortisol, oestradiol-17 beta, progesterone, testosterone, thyroxine, theophylline, cholesterol, creatinine, glucose, total triacylglycerols and uric acid. All determinations were done in parallel in the two laboratories, independently and within certain time constraints. The general measurement design consisted of duplicate measurement of each sample on three different occasions. In each laboratory, rigorous internal quality control was performed according to predefined analytical quality specifications. This was done using certified reference materials. If not available, control materials targeted before by the two laboratories were utilized. Here we present the results of the cooperation during five years. We discuss the precision and accuracy achieved, the between-laboratory agreement and the total analytical error. For the hormones and theophylline, the mean overall coefficient of variation for both laboratories (calculated from the measurements on three days) was always < 2%, for the substrates < 1%. For all substances, the method bias (estimated from several measurement series over the five years) was < 1%, and the average deviation of the results between the two laboratories was < 1.2%. The maximum total analytical error was in all cases < 3%. These data demonstrate that current reference methodology is able to guarantee a stable level of high quality of performance, and that reference laboratories of today are capable of providing, in due time, adequate service in the framework of accuracy-based harmonization of methods in routine laboratory medicine.