Aim: Biotin in human serum is a potential interfering factor for streptavidin-biotin-based assays. We aimed to evaluate the effective half-life of biotin and biotin metabolites, and establish a pharmacokinetic (PK) model to simulate the time taken for the biotin concentration to fall below a series of thresholds. Materials & methods: PK properties of biotin (5, 10 and 20 mg daily) were evaluated in healthy participants. Biotin serum concentrations were simulated for high-dose regimens (1 mg daily to 300 mg q.i.d.) using a population PK model. Results: Washout periods required for biotin concentrations to reach thresholds ranging from 10 to 100 ng/ml were successfully simulated. Conclusion: Our simulations provide valuable guidance on biotin washout periods necessary to avoid false assay results. Immunoassays that allow rapid measurement of analytes can be vital for the correct diagnosis of a broad range of diseases [1]. The interaction of streptavidin and biotin has been utilized for the development of robust and highly sensitive immunoassays by many manufacturers (Abbott, Beckman Coulter, Ortho Clinical Diagnostics, Roche Diagnostics, Siemens Healthcare Diagnostics and others). Biotin, a water-soluble vitamin, is a small and stable molecule that can be conjugated to many proteins without significantly affecting their biological activity; this interaction is the strongest known noncovalent binding between a protein and a ligand [2].Exogenous biotin has the potential to interfere with streptavidin-biotin-based assay results. The impact of interference on test results can be the generation of falsely high values, obtained when using a competitive assay design, whereby an excess of biotin in the specimen competes with biotinylated analog for binding sites on streptavidin. Alternatively, when using a sandwich assay design, an excess of biotin in the specimen can displace biotinylated antibodies, which can generate falsely low values [3]. Reports of biotin interference leading to incorrect biochemical diagnoses in both adults and children have been published previously, along with warnings to clinicians and pathologists to interpret unexpected assay results with caution and consider the potential effect of biotin interference before making a diagnosis [4][5][6][7].The normal serum concentration of biotin is very low; published average values range from below 0.1 to 0.8 ng/ml [8,9]. The adequate daily intake of biotin is 30 μg/day [10] and biotin deficiency is rare as the majority of diets contain enough biotin for this to be reached. However, biotin is increasingly being marketed as a lifestyle supplement which is claimed to strengthen hair and nails, despite no scientific confirmation of these benefits [11]. The unregulated, over-the-counter (OTC) product is available in doses ranging from 50 μg found in multivitamin

The use of a correction factor is recommended based on the differences in European and Asian MoM values. Developing country-specific medians in larger study populations can help identify clinical relevant differences and give the opportunity to explore a more accurate risk calculation.

Screening for fetal trisomy 21 (T21) in the first trimester includes analysis of the serological markers pregnancy-associated plasma protein A (PAPP-A) and free β-choriogonadotropin (free βhCG). With the recent launch of these assays on the cobas e and Elecsys platforms, we investigated their clinical and analytical performance.We conducted a multicenter study in 5397 pregnancies including 108 cross-sectional collected repository cases with verified fetal T21 at 8–14 weeks of gestation. A technical validation of the Roche ElecsysThe imprecision of the Elecsys free βhCG and PAPP-A assays was between 1.0% and 2.8%, and both assays showed correlation to Kryptor (free βhCG 0.981; PAPP-A 0.987), AutoDELFIA (free βhCG 0.995; PAPP-A 0.979) and IMMULITE assays (free βhCG 0.983; PAPP-A 0.983). With a cut off at 1:300 the overall sensitivity of the screening including nuchal translucency reached 94% for a 3% false positive rate.The Roche Elecsys free βhCG and PAPP-A are suitable and reliable assays for first trimester T21 risk assessment. Both assays were approved and recommended by the FMF.