Online Supercritical Fluid Extraction Coupled with Inductively Coupled Plasma Mass Spectrometry for Monitoring Titanium Release from Orthopedic Implants

Background: Titanium-based orthopedic implants can release titanium in chloride, acidic and protein-containing biological environments. Conventional acid-digestion ICP-MS can be used to determine the total titanium content released from the implants, but requires substantial mineral-acid consumption and multiple sample-handling steps. Objective: To develop and evaluate a 3,4,3-(LI-1,2-hydroxypyridinone)-assisted online supercritical fluid extraction–ICP-MS method for the determination of extractable titanium released from commercially pure titanium and Ti-6Al-4V implants. Methods: Implant samples were incubated for 21 days in phosphate-buffered saline, simulated body fluid, acidic inflammatory medium, and an albumin-containing matrix. Extraction temperature, pressure, time, pH, modifier, and ligand concentration were optimized. Linearity, detection and quantification limits, recovery, precision, matrix effects, carryover, robustness, and stability were assessed. Results: Optimal extraction was achieved at 60 °C, 25 MPa, 20 min, pH 5.5, 15% methanol, and 50 µmol L−1 ligand. The method was linear over 0.10–5.00 µg L−1, with R2 values of 0.9987 and 0.9979 in phosphate-buffered saline and albumin matrix, respectively. Using the 3σ/S, detection limits were 0.033 and 0.044 µg L−1. Recoveries were 98.4–101.2% and 94.2–96.1%, respectively. Titanium release increased with time and was highest under acidic conditions. Ti-6Al-4V consistently released slightly more titanium than commercially pure titanium across the evaluated model media. Conclusions: The method reduced acid use and handling, but requires specialized high-pressure instrumentation. Conventional acid-digestion ICP-MS remains more accessible for routine total titanium analysis. Clinical-matrix and tribocorrosion validation remain necessary.