Direct Measurement of Free Copper in Serum or Plasma Ultrafiltrate

Copper is an essential element and, under conditions of overload, a toxicant. A dramatic example of copper toxicity is Wilson disease (WO), a treatable but often fatal condition that is difficult to diagnose and monitor. A method for direct measurement of free copper concentrations in serum or plasma ultrafiltrate by inductively coupled mass spectrometry was developed and validated to assist with diagnosis and monitoring WD. The method was shown to be accurate (94%-109% recoveries), linear (0.5-800 mu g/dL [0.08-126 mu mol/L]), and precise (coefficient (of variation, < 15% over the analytic measurement range). A reference interval (0-10 mu g/dL [0-1.6 mu mol/L]) was determined parametrically with 13 7 healthy adult (20-59 years) blood donors. No statistically significant difference was observed in males (n = 69) vs females (n = 68). Free copper concentrations for patients diagnosed with WO were at least 6-fold greater than the upper limit of the reference interval before treatment but fell within the reference interval after treatment.