The clinical chemist has a pivotal role in recognizing analytical interference of medication in diagnostic laboratory assays [1, 2]. Timely signaling of interference can lead to a reduction in diagnostic errors and therefore to increased patient safety and quality of care. In our hospital, a 26-year-old man presented with amiodarone-induced thyrotoxicosis (TSH< 0.015 mIU/L, FT4> 77 pmol/L), for which a combined therapy of thiamazole (Strumazol 30 mg, one time each day) and sodium perchlorate (500 mg, two times each day) was started (written consent was obtained from the patient). Soon afterward unexplainably low sodium (Na+) and ionized calcium (Ca2+) concentrations were obtained, which prompted the endocrinologist to contact the laboratory, not sure whether electrolyte treatment should be started. The concentrations, measured on the RAPIDPoint 500 blood gas analyzer (Siemens Healthineers, Erlangen, Germany), were highly discrepant with the results of the AU5811 chemistry analyzer (Beckman–Coulter, Brea, CA, USA). Na+ levels were about 10 mmol/L lower at RAPIDPoint 500 (Figure 1). In addition, ionized Ca2+ levels as low as 0.5 mmol/L (reference interval: 1.15–1.32 mmol/L) were reported, while total calcium levels were normal.

Perchlorate is a potent competitive inhibitor of the sodium/iodide symporter, which is used in the perchlorate discharge test to identify organification defects and for treating amiodarone-induced thyrotoxicosis type I [3]. Interference of perchlorate with ionized Ca2+ measurements has been described before for several blood gas analyzers, but no effects on Na+ levels were mentioned [4, 5]. Therefore, we compared electrolyte measurements at RAPIDPoint 500 and AU5811 in the presence of a range of perchlorate concentrations. As many wards in our hospital rely on i-STAT point-of-care analyzers (Abbott Laboratories, Chicago, IL, USA) for electrolyte measurements, we also included this analyzer in our comparison. Sodium perchlorate concentrations in vivo depend on dose, intake frequency, distribution volume and kidney function. In 11 patients receiving perchlorate, plasma concentrations ranging from 0.031 to 2.75 mmol/L were obtained by Gruber et al. using a perchlorate-selective electrode [5]. Therefore, we decided to analyze sodium, potassium (K+), chloride (Cl−) and calcium (RAPIDPoint/i-STAT: ionized Ca2+; AU5811: total calcium) levels in the presence of perchlorate with plasma concentrations ranging from 0.05 to 4 mmol/L (sodium perchlorate was dissolved and diluted). We used pooled anonymous leftover blood samples (BD Vacutainer lithium heparin 4.0 mL) for which a maximal pH difference of 0.05 within 1 dilution series (max. 0.03 mmol/L ionized Ca2+) was allowed. RAPIDPoint 500 and i-STAT analyses were performed in whole blood, while AU5811 analyses were carried out in derived plasma. The measured Na+ levels were corrected for the added amount as part of sodium perchlorate. Perchlorate levels of 1 mmol/L and higher induced clinically significant decreases of the Na+ concentration when measured on RAPIDPoint 500 (Figure 2A). At 4 mmol/L, perchlorate caused 11.5 mmol/L (8.2%) reduction of the Na+ concentration (Supplementary Figure 1A). Na+ measurements at i-STAT and AU5811, however, were hardly influenced by perchlorate. Cl− levels at RAPIDPoint 500 significantly increased in response to perchlorate, with a maximal increase of 21.3 mmol/L, while AU5811 Cl− levels only showed a minor rise (Figure 2B, Supplementary Figure 1B). Perchlorate interference with i-STAT Cl− analysis was not investigated, because the CG8+ cartridge used in