Preparation and certification of creatinine and urea reference materials with certified purity as a traceability source in clinical chemical measurements

Purity certified reference materials (CRMs) are playing a key role in metrological traceability, because they form the basis for many traceability chains in chemistry. Recently, the National Metrology Institute of Japan (NMIJ) has developed two purity CRMs for creatinine (NMIJ CRM 6005-a) and urea (NMIJ CRM 6006-a), because the concentrations of these two compounds are frequently measured in clinical laboratories for monitoring the renal functions. In the certification of purity CRMs, it is essential that the materials have been thoroughly characterized for purity, and the purity should preferably be determined directly by a primary method of measurements. In the development of these two CRMs, we used the purified materials as candidates. The certified values were assigned based on the results of two different methods; acidimetric titration and nitrogen determination by the Kjeldahl method. Since both methods cannot distinguish some impurities from the target compounds, major impurities in the candidate materials were also identified, quantified, and subtracted. These CRMs can provide a traceability link between routine clinical methods and SI units.