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Published on: May 4, 2020
An inductively coupled plasma mass spectrometry method for relative free copper determination and generation of a
P Wainwright1, D Wadey1, P Cook1
1Department of Clinical Biochemistry, University Hospital Southampton, Southampton, UK.
Insights
This study introduces a new method to measure free copper in plasma, crucial for diagnosing and monitoring Wilson's disease in children. The validated technique provides the first pediatric reference interval, improving diagnostic accuracy for this rare genetic disorder.
Area of Science:
- Biochemistry
- Clinical Chemistry
- Pediatric Medicine
Background:
- Current Wilson's disease diagnosis relies on caeruloplasmin testing, which has limitations.
- 24-hour urine copper collection, used for patient monitoring, is inaccurate in children.
- Direct plasma free copper measurement methods exist, but lack pediatric reference data.
Purpose of the Study:
- To develop and validate a method for measuring plasma free copper in children.
- To establish the first pediatric reference interval for plasma free copper.
- To improve Wilson's disease diagnosis and monitoring in pediatric patients.
Main Methods:
- Developed and validated an ultrafiltration inductively coupled plasma mass spectrometry (ICP-MS) method for plasma free copper.
- Generated a pediatric reference interval using 85 plasma samples from children.
- Ensured method accuracy and precision with low analytical coefficients of variation (5-7%).
Main Results:
- The ultrafiltration ICP-MS method showed no significant copper contamination.
- The method demonstrated high accuracy and precision.
- The first pediatric reference interval for plasma free copper was successfully established.
Conclusions:
- The validated ultrafiltration ICP-MS method offers a reliable way to measure plasma free copper.
- This method, with the new pediatric reference interval, can aid in diagnosing and monitoring Wilson's disease in children.
- Plasma free copper measurement holds potential for improved management of Wilson's disease in both pediatric and adult populations.
Abstract:
Background Diagnosis of Wilson's disease is currently performed using caeruloplasmin as a first-line screening test; however, this test has well-described limitations. Monitoring of known Wilson's disease patients often uses 24-h urine collection; however, this is inaccurate in children. Methods for directly measuring plasma free copper have been described, but no reference interval data exist for a paediatric population. Methods An inductively coupled plasma mass spectrometry method for measuring free copper was developed and validated, using ultracentrifugation. A paediatric reference interval was generated using 85 plasma samples from children attending outpatient clinics at University Hospital Southampton. Results Results showed no significant contamination of copper using the ultracentrifugation technique, and validation showed the method was accurate and precise with an analytical coefficient of variation between 5 and 7% depending on the concentration of free copper. Conclusions We describe the use and validation of an ultrafiltration inductively coupled plasma mass spectrometry method for plasma free copper with the first published paediatric reference interval. Free copper could provide much needed assistance for the monitoring of Wilson's disease in children and also for adults.
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