Migration from RIA to LC-MS/MS for aldosterone determination: Implications for clinical practice and determination of plasma and urine reference range intervals in a cohort of healthy Belgian subjects

Abstract Background Aldosterone measurement is critical for diagnosis of primary aldosteronism and disorders of the renin-angiotensin system. We developed an LC-MS/MS method for plasma and urinary aldosterone and compared it to our RIA method. We present a reference interval study for a Belgian population. Methods 68 plasma and 23 urine samples were assayed for as part of a method comparison. For the reference interval study, we enrolled 282 healthy Caucasian volunteers (114 Male: mean age 35 ± 11 y and 168 Female: mean age 42 ± 13 y). A subset of 139 healthy volunteers agreed to a 24-h urine collection. For the method validation, 5 plasma and 8 urine pools were run in triplicate and quadruplicate, respectively, on 3 different days. Results Between-run imprecision (CV) was 2.8–5.1% for plasma and 4.5–8.6% for urine, except at the low urine concentration of 2.99 nmol/L where a CV of 15.4% was observed. The limit of quantitation was 0.04 nmol/L for plasma and 6.65 nmol/L for urine. Recoveries, based on spiking experiments into natural matrix, did not differ significantly from 100%. Regression comparisons showed that, on average, RIA generated results were 59% and 11% higher than LC-MS/MS for plasma and urine, respectively. The MS reference interval we propose for plasma aldosterone is 0.07 nmol/L–0.73 nmol/L for women and 0.04 nmol/L–0.41 nmol/L for men. No gender difference was observed for urine aldosterone. The reference interval was determined to be Conclusions The LC-MS/MS method was validated and reference intervals for plasma and urine were established. A significant bias between RIA and LC-MS/MS was noted.