Liquid chromatography-tandem mass spectrometry-based recalibration reduces inter-platform variability in aldosterone...

Accurate aldosterone (ALD) measurement is vital in managing diseases such as primary aldosteronism (PA). However, inter-platform inconsistency across chemiluminescence immunoassay (CLIA) platforms complicates clinical decisions. This study conducted the largest comparison of CLIA platforms (six CLIA platforms) and one liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay for ALD detection to date, systematically evaluated inter-platform consistency and explored the role of recalibration strategy based on LC-MS/MS in improving consistency among CLIA platforms.

Fifty pooled clinical plasma samples were used to evaluate ALD levels across six different CLIA platforms and one LC-MS/MS assay. Friedman's test, Spearman correlation, Passing-Bablok regression, and Bland-Altman analysis were used to evaluate the consistency among assays. In addition, CLIA platforms were recalibrated against LC-MS/MS using regression equations with five pooled clinical plasma samples as calibration materials, and consistency was evaluated before and after recalibration.

LC-MS/MS yielded significantly lower ALD levels than six CLIA platforms (median: 120.75 vs. 129.29 to 216.25 pg/mL, P < 0.05). All assays correlated strongly (R ≥ 0.955), yet regression parameters revealed most slopes deviated from 1 (0.909 to 1.444) and intercepts ranged from -31.424 to 52.272 pg/mL. Bland-Altman plots demonstrated large relative mean differences (-2.396 % to 55.876 %) between assays. The recalibration process significantly reduced relative mean differences, whereas it showed limited improvement in addressing both proportional and systematic biases.

These findings demonstrate that the consistency among CLIA platforms and LC-MS/MS assays is suboptimal. Actionable design strategies for developing recalibration coefficients, which reduce relative mean differences, are provided for CLIA platforms, emphasizing the necessity for standardized calibration to reduce inter-platform variability in clinical ALD measurement. The persistent proportional and systematic biases underscore the urgency for optimization in calibration strategy and detection methodology.