Elements in human serum—CCQM-K139
Authors: Shin Richard , Dewi Fransiska , Tong Benny , Wah Leung Ho , Saxby David , Armishaw Paul , Ivanova Veronika , Feng Liuxing , Wang Jun , Busto M Estela del Castillo , Fisicaro Paola , Rienitz Olaf , Fung Wai-Hong , Yau Michael Ho-pan , Yim Yong-Hyeon , Buzoianu Mirella , Can Suleyman Z , Ari Betul , Cankur Oktay , Infante Heidi Goenaga , Pérez-Zambra Ramiro , Ferreira Elizabeth , Long Stephen , Davis W. Clay , Easley Regina A. 
Published: February 2018

Elements in human serum serve as important biomarkers and their levels reflect the well-being of an individual. Electrolytes such as sodium (Na) and chloride (Cl) are crucial in maintaining the normal distribution of water, osmotic pressure and electrical neutrality in the body. Trace element such as copper (Cu) plays a part in many oxidation-reduction reactions and metalloenzymes. The majority of selenium (Se) exists as selenoproteins which are cofactors in the glutathione peroxidase activity that protects the body against free radicals. Phosphorus (P) is required for strong bones and teeth. It is also indispensable for growth, maintenance and repair of tissues and cells.
The key comparison CCQM-K139: elements in human serum was coordinated by the Health Sciences Authority, Singapore. This comparison aimed to enable participating National Metrology Institutes (NMIs) and Designated Institutes (DIs) to demonstrate their competence in the determination of elements (electrolytes and essential elements) in human serum. The five measurands (Na, Cl, Cu, Se and P) selected for this comparison were not covered in the last two comparisons in the clinical area (CCQM-K14 and CCQM-K107) and offered different analytical challenges. Their concentration levels were within the normal biological range. They were also within the range of existing calibration and measurement capability (CMC) claims in the International Bureau of Weights and Measures' Key Comparison Database (BIPM KCDB). Ten institutes participated in the comparison for Na, eight for Cl, eleven for Cu, six for Se and eight for P.
For the analysis of Na, Cu, Se and P, most of the participating institutes employed microwave-assisted digestion and acid digestion (with or without heating) sample dissolution. For the analysis of Cl, in addition to the microwave-assisted digestion and acid digestion, a wider variety of techniques were employed. These included matrix separation, alkaline extraction and coulometric titration. Inductively coupled plasma mass spectrometry (ICP-MS) and inductively coupled plasma optical emission spectrometry (ICP-OES) were the two most commonly used instrumental techniques. Other techniques used included ion chromatography (IC), flame atomic absorption spectrometry (FAAS), titration and micro-coulometry.
The medians were used as the estimators of Key Comparison Reference Values (KCRVs) for all measurands. The KCRVs (± standard uncertainty) for Na, Cl, Cu, Se and P (in mg/kg) were 3346 (± 14), 3871 (± 22), 1.151 (± 0.007), 0.1292 (± 0.0007) and 125.70 (± 0.35), respectively. The k-factor of 2 was used for the estimation of the expanded uncertainties of the KCRVs. The degree of equivalence and its associated uncertainty were calculated for each submitted result. For the five measurands, most participating institutes were able to demonstrate their capabilities in the determination of elements in human serum.
CMC claims based on elements covered in this study may include other elements with similar core competencies, such as zinc (Zn), potassium (K), magnesium (Mg), calcium (Ca) and iron (Fe), in a wide range of biological materials. The measurands should be at similar concentration range and analysed using the same measurement technique(s) applied in this key comparison.

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To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/.
The final report has been peer-reviewed and approved for publication by the CCQM, according to the provisions of the CIPM Mutual Recognition Arrangement (CIPM MRA).