Electrochemical viscosity correction for robust salivary ionomics via redox probe voltammetry

Accurate quantification of small ions in mucin-rich biofluids such as saliva is often compromised by viscosity-dependent diffusion effects. We propose an electrochemical viscosity-correction strategy based on the peak potential separation (ΔE_p) of the redox probe [Fe(CN)₆]^3-/4- measured by cyclic voltammetry. The ΔE_p value under the fixed experimental conditions reflected sample-specific diffusion behavior and was employed as a correction factor for ion concentrations determined by capillary electrophoresis (CE). The relationship between ΔE_p and mucin concentration was validated using model viscosity standards, demonstrating a strong logarithmic correlation within physiologically relevant ranges. Application of the ΔE_p-based correction reduced dispersion of salivary ion measurements compared with conventional normalization approaches such as specific gravity and total protein correction. The analytical utility of the method was first examined through repeated measurements in a single individual undergoing a cold pressor test (CPT). Furthermore, its robustness was evaluated in an independent cohort of 12 healthy participants (6 cold stimulation and 6 control participants), where corrected ion profiles showed clearer differentiation between experimental conditions than uncorrected data. This ΔE_p-based correction approach provides a rapid, non-destructive, and low-volume (10 μL) analytical strategy to minimize viscosity-induced bias in ion analysis of complex biological matrices. The method enhances the robustness of CE-based ionomics and offers a broadly applicable framework for analytical measurements in non-Newtonian biofluids.