Multielement Detection of Nonmetals by Barium-Based Post-ICP Chemical Ionization Coupled to Orbitrap-MS

Prevalence of F, Cl, S, P, Br, and I in pharmaceuticals and environmental contaminants has promoted standard-free quantitation using analyte-independent heteroatom responses in inductively coupled plasma (ICP)-MS. However, in-plasma ionization challenges and element-dependent isobaric interference removal methods have hampered the multielement nonmetal detection in ICP-MS. Here, we examine an alternative approach to enhance multielement detection capabilities. Analytes are introduced into an ICP leading to post-plasma formation of HF, HCl, H₃PO₃, H₂SO₄, HBr, and HI, which are then chemically ionized to BaF⁺, BaCl⁺, BaH₂PO₃⁺, BaHSO₄⁺, BaBr⁺, and BaI⁺ via reactions with barium-containing ions supplied by a nanospray. Subsequent ion detection by high-resolution MS provides an element-independent approach for resolving isobaric interferences. We show that elemental response factors using these ions are linear within 2 orders of magnitude and independent of analytes’ chemical structures. Using a single set of operating parameters, detection limits <1 ng/mL are obtained for Cl, Br, I, and P, while those for F and S are 1.8 and 6.2 ng/mL, respectively, offering improved multielement quantitation of nonmetals. Further, insights into ionization mechanisms indicate that the reactivities of reagent ions follow the order BaNO₂⁺ > BaHCO₂⁺ > Ba(H₂O)_n²⁺ ∼ BaCH₃CO₂⁺. Notably, the least reactive ions are generated directly by nanospray, suggesting that modification of these ions via interaction with plasma afterglow is critical for achieving good sensitivities. Moreover, our experiments indicate that the element-specific plasma products follow the order HF < H₂SO₄ ∼ HCl < H₃PO₃ ∼ HBr ∼ HI for their propensity to react with reagent ions. These insights provide guidelines to manage matrix effects and offer pathways to further improve the technique.