Candidate reference measurement procedure for determination of urea in serum by liquid chromatography-tandem mass spectrometry

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Urea is an important indicator of liver and kidney disease, and very frequently determined in clinical chemistry. The reference measurement procedures (RMPs) for serum urea recognized by the Joint Committee for Traceability in Laboratory Medicine are spectrophotometry, and isotope dilution (ID)-mass spectrometry (MS) coupled with gas chromatography. This study investigated a candidate RMP (cRMP) for detecting serum urea directly via ID-liquid chromatography (LC)-MS/MS, without derivatization, which simplifies pre-processing samples. The cRMP was developed and evaluated relative to the recognized RMP, inter- and intra-laboratories. The intra-precisions were 1.35%, 1.98% and 1.47% at 4.95, 24.74 and 31.36 mmol/L, respectively; inter-precision was 2.10%, 2.60% and 2.10%. The relative bias for the measurement of standard human serum (SRM 909c) was –0.49%. The relative biases were 0.41% and 0.02% for IFCC-RELA (International Federation of Clinical Chemistry and Laboratory Medicine-External Quality Assessment Scheme [EQAS] for reference laboratories) 2015A and 2015B. The linearity response between 2.4 mmol/L and 53.7 mmol/L was R2 = 0.9989. No carryover, ion suppression, or interference was detected. Correlation was acceptable with the reference spectrophotometry (R2 = 0.9985, P < 0.0001). Between our laboratory and other reference laboratories, the absolute deviation range for IFCC-RELA 2016A and 2016B was from –0.63 to 1.52 mmol/L. This well-characterized cRMP for urea can provide a base of accuracy for the traceability of clinical systems.HighlightsThis paper describes the development and evaluation of a candidate reference measurement procedure (cRMP) for serum urea that uses a LC-MS/MS method. This novel cRMP directly detects urea without derivatization, which makes the pre-processing of samples very simple compared to the reference methods now recognized by the JCTLM.The performance of this cRMP is well characterized, with good demonstrated precision and accuracy.This cRMP could facilitate the implementation and standardization of procedures and testing results for serum urea among clinical laboratories.

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