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Copper is an essential trace element, participating in many biochemical pathways throughout the human body. In the healthy adult, approximately 100 mg of copper is stored throughout the body, primarily [...], * Context.--Clinical testing for Wilson disease (WD) is potentially challenging. Measuring the fraction of labile bound copper (LBC) to total copper may be a promising alternative diagnostic tool with better sensitivity and specificity than some current biomarker approaches. A dual filtration-based inductively coupled mass spectrometry (ICPMS) assay to measure LBC in serum was developed. Objective.--To establish a reference interval for LBC and LBC to total copper (LBC fraction) in a healthy adult population, and to examine associations between total copper, LBC, and LBC fraction with age, sex, menopausal status, hormone replacement therapy, and supplement use. Design.--Serum samples were collected from healthy male (n = 110) and female (n = 104) patients between the ages of 19 and 80 years. Total copper and LBC were analyzed using ICP-MS. Results were used to calculate the LBC fraction. Reference intervals were calculated for the 2.5th and 97.5th percentiles for both LBC and LBC fraction. Results.--The reference intervals for LBC were determined to be 13 to 105 ng/mL and 12 to 107 ng/mL for female and male patients, respectively. The reference intervals for the LBC fraction were 1.0% to 8.1% and 1.2% to 10.5% for female and male patients, respectively. No significant associations were found regarding age, menopausal status, hormone replacement therapy, or vitamin and supplement use. Conclusions.--Sex-specific reference intervals have now been established for LBC and LBC fraction. These data in conjunction with further testing of WD populations can be used to assess the sensitivity and specificity of LBC fraction in screening, monitoring, and diagnosis. doi: 10.5858/arpa.2023-0259-OA)

Background Due to the ability of metal ions to cross the blood–brain barrier, there has been interest in analyzing cerebrospinal fluid (CSF) for trace element concentrations to investigate possible correlations with neurodegenerative diseases. In this study, Sarstedt polypropylene CSF collection tubes were analyzed to determine the contamination levels of aluminum, titanium, chromium, manganese, cobalt, nickel, molybdenum, gadolinium, vanadium, arsenic, cadmium, mercury, lead, thallium, selenium, copper, zinc, and iron. Methods Sarstedt polypropylene CSF collection tubes from 2 separate lots (n = 10 per lot) were filled with a 2 mL aliquot of a CSF pool with known element concentrations. After 24 hours of leaching at room temperature, all 18 elements were analyzed via inductively coupled plasma mass spectrometry (ICP-MS). Results were subtracted from the initial pool concentration to determine contamination levels. Results No detectable contamination above the assay limit of detection was found in 11 analytes. Molybdenum and selenium contamination was measured in all tubes, and aluminum, titanium, manganese, thallium, and zinc had minimal levels of sporadic detectable contamination in 25% or fewer of the tubes tested. Conclusions Sarstedt polypropylene CSF tubes are an acceptable collection tube for the analysis of most assessed metals in CSF. [ABSTRACT FROM AUTHOR]

Objective: To investigate the effect of CRYSVITA® (burosumab‐twza) on FGF23 measurements in an intact and a C‐terminal immunoassay. Methods: An intact serum FGF23 (MedFrontier) and a C‐terminal plasma FGF23 assay (Immutopics) were used. Serum/plasma pools were spiked to span the burosumab therapeutic range (1.4–11.3 μg/ml) and FGF23 recovery was assessed. Patient serum and plasma samples obtained pre and post‐burosumab treatment were evaluated on both assays and compared with corresponding phosphorus measurements Results: Spiking burosumab (1.4–11.3 μg/ml) into sample pools resulted in a dose‐dependent negative analytical interference on intact FGF23 measurements and no significant interference for C‐terminal FGF23 measurements. However, more than a 500‐fold median increase (post‐ vs. pre‐burosumab administration) in in vivo FGF23 concentrations were observed by both assays. Conclusions: Therapeutic concentrations of burosumab result in a negative analytical interference of the intact, but not the C‐terminal FGF23 immunoassay. Despite this in vitro analytical interference in the intact assay, relatively large elevations of both intact FGF23 and C‐terminal FGF23 measurements were observed in vivo following burosumab administration. Following burosumab administration, FGF23 measurements must be interpreted within the clinical context of the patient and other relevant biomarker results. Summary: This article describes a negative analytical interference by burosumab in an intact FGF23 immunoassay. The recovery of C‐terminal FGF23 is not significantly affected by the presence of burosumab. In vivo, both assays demonstrate extreme FGF23 elevations in the presence of the drug. Furthermore, the measurement of FGF23 blocked by burosumab is not clinically useful regarding hypophosphataemia. [ABSTRACT FROM AUTHOR]