Quality specifications and their daily application to evaluate the accuracy of reference measurements for serum concentrations of 25-hydroxyvitamin D3 and 25-hydroxyvitamin D2.

BACKGROUND: Reference measurement procedures (RMP) have rigorous accuracy specifications. For total 25-hydroxyvitamin D, 25(OH)D, bias ≤1.7% and CV ≤5% are recommended. These quality specifications are impractical for minor analytes, such as 25(OH)D2. Furthermore, documentation on RMP quality performance specifications for the individual 25(OH)D metabolites and their daily application are missing. METHODS: To assess accuracy, we used zeta-scores. Daily, 5-10 specimens (duplicate) and 3 reference materials (singleton or duplicate) were measured for 25(OH)D3 and 25(OH)D2 using JCTLM-accepted LC-MS/MS RMPs. Protocols were repeated on 3-4 occasions to generate campaign results. We used separate zeta-score acceptability criteria for daily (≤|2|) and campaign (≤|1|) evaluations. Allowable imprecision was determined experimentally. RESULTS: Across 7 campaigns, unacceptable daily zeta-scores required repeating 2 runs for 25(OH)D3 and 5 runs for 25(OH)D2. Hence, the zeta-scores of acceptable reference material results indicated high accuracy. The allowable imprecision for the RMPs was ≤5% (daily) and ≤ 3% (campaign) for 25(OH)D3 and ≤ 7% (daily) and ≤ 4% (campaign) for 25(OH)D2, respectively. CONCLUSIONS: Using zeta-scores and experimentally derived imprecision, we developed a straightforward approach to assess the acceptability of individual 25(OH)D reference measurements, providing also much-needed practical accuracy specifications for 25(OH)D2.

Development of a Standard Reference Material for metabolomics research.

The National Institute of Standards and Technology (NIST), in collaboration with the National Institutes of Health (NIH), has developed a Standard Reference Material (SRM) to support technology development in metabolomics research. SRM 1950 Metabolites in Human Plasma is intended to have metabolite concentrations that are representative of those found in adult human plasma. The plasma used in the preparation of SRM 1950 was collected from both male and female donors, and donor ethnicity targets were selected based upon the ethnic makeup of the U.S. population. Metabolomics research is diverse in terms of both instrumentation and scientific goals. This SRM was designed to apply broadly to the field, not toward specific applications. Therefore, concentrations of approximately 100 analytes, including amino acids, fatty acids, trace elements, vitamins, hormones, selenoproteins, clinical markers, and perfluorinated compounds (PFCs), were determined. Value assignment measurements were performed by NIST and the Centers for Disease Control and Prevention (CDC). SRM 1950 is the first reference material developed specifically for metabolomics research.