Determination of ultra-trace levels of titanium in human serum using inductively coupled plasma tandem mass spectrometry based on O2/H2 reaction gas

Highlights: • Interference-free determination of ultra-trace levels of Ti in human serum by ICP-MS/MS. • Spectral interferences were eliminated using O₂/H₂ as the reaction gas. • The limit of detection of Ti isotopes was approximately 0.78–7.20 ng L⁻¹. • The high sensitivity of ultra-trace titanium determination in human serum was realized. This study proposes a new strategy to determine ultra-trace Ti in human serum using inductively coupled plasma tandem mass spectrometry (ICP-MS/MS). The human serum samples were diluted with 1% (v/v) HNO₃, followed by the determination of ultra-trace Ti using ICP-MS/MS. In the MS/MS mode, a small amount of H₂ was mixed with O₂ (the reaction gas) in a collision reaction cell (CRC) to form an O₂/H₂ reaction mixture, and then, the conversion of Ti⁺ to TiO⁺ was determined by the O₂ mass shift method. High concentrations of Ca, S, and P in human serum were ionized in plasma, and the formed Ca⁺, SO⁺, and PO ⁺ reacted with O₂ in CRC to form CaO⁺, SO₂⁺, and PO₂⁺ to interfere with the determination of TiO⁺. We employed the mass shift reaction of H₂ and oxide ions to eliminate this interference. This method was evaluated using the human serum sample spike recovery experiment and comparative analysis by sector field (SF)-ICP-MS. The results showed that using reaction gas mixture O₂/H₂ reduced the background equivalent concentration (BEC) of Ti and improved sensitivity. The values determined by this method were consistent with the SF-ICP-MS values, which confirmed its accuracy and reliability. The limit of detection (LOD) of Ti was 0.78–7.20 ng L⁻¹, the recovery was 96.0%–104%, and the relative standard deviation (RSD) was 2.0%–4.2%. This method has solved the problem that the determination of ultra-trace Ti in human serum cannot be accurately determined using O₂ reaction mode. It realizes the interference-free and highly sensitive determination of the ultra-trace Ti in samples with high levels of Ca, S, and P and provides a new technique for high-throughput and accurate determination of ultra-trace Ti in human serum.