Ion chromatography for inorganic phosphate in human serum: a candidate reference measurement procedure and commutable certified reference material

Accurate measurement of inorganic phosphate in human serum is critical for clinical diagnostics, yet the metrological infrastructure supporting this analyte remains limited, with only one reference measurement procedure (RMP) listed by the Joint Committee for Traceability in Laboratory Medicine (JCTLM) and no certified reference material (CRM) available for inorganic phosphate in human serum. This study addresses both gaps through the development and validation of an ion chromatography (IC) method with suppressed conductivity detection for the quantification of inorganic phosphate in human serum, with calibration standards traceable to SI units via NIST SRM 3186. Excellent linearity (R² ≥ 0.999), precision (coefficient of variation, CV < 1%), and spike recoveries close to 100% were achieved, with expanded measurement uncertainties below 2% (k = 2), fulfilling optimal-level analytical performance specifications derived from biological variation data over a clinically relevant inorganic phosphate range in serum, supporting the suitability of this IC method as a candidate RMP. The method was applied to certify the inorganic phosphate concentration in frozen human serum (HRM-2023A) as 1.120 ± 0.023 mmol/L (k = 2), representing the first metrologically traceable CRM for inorganic phosphate in human serum. Commutability of HRM-2023A was confirmed against the Roche COBAS C311 and Abbott Alinity C clinical platforms using a regression-based approach with 95% prediction intervals. Good agreement with both routine analysers was demonstrated using 28 anonymised patient samples, with differences predominantly within the Royal College of Pathologists of Australasia (RCPA) acceptable limits of ± 8%. This work presents IC as a strong candidate RMP for inorganic phosphate in serum, supported by a commutable, SI-traceable CRM, addressing critical gaps in metrological infrastructure and supporting improved harmonisation of inorganic phosphate measurements in clinical laboratories.