DETERMINATION OF REFERENCE METHOD VALUES BY ISOTOPE-DILUTION GAS-CHROMATOGRAPHY MASS-SPECTROMETRY - A 5 YEARS EXPERIENCE OF 2 EUROPEAN REFERENCE LABORATORIES

We report on the cooperation of two European Reference Laboratories fo r the determination of reference method values in serum based material s intended for use in internal accuracy control and external quality a ssessment. Reference method values were determined by isotope dilution -gas chromatography/mass spectrometry for aldosterone, cortisol, oestr adioI-17 beta, progesterone, testosterone, thyroxine, theophylline, ch olesterol, creatinine, glucose, total triacylglycerols and uric acid. All determinations were done in parallel in the two laboratories, inde pendently and within certain time constraints. The general measurement design consisted of duplicate measurement of each sample on three dif ferent occasions. In each laboratory, rigorous internal quality contro l was performed according to predefined analytical quality specificati ons. This was done using certified reference materials. If not availab le, control materials targeted before by the two laboratories were uti lized. Here we present the results of the cooperation during five year s. We discuss the precision and accuracy achieved, the between-laborat ory agreement and the total analytical error. For the hormones and the ophylline, the mean overall coefficient of variation for both laborato ries (calculated from the measurements on three days) was always < 2%, for the substrates < 1%. For all substances, the method bias (estimat ed 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%. Thes e data demonstrate that current reference methodology is able to guara ntee 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 i n routine laboratory medicine.