Hydrogen sulfide exhibits many characteristics of an endogenous biological mediator and is present at low baseline levels in tissues and blood. A large body of evidence suggests that exogenously applied sulfide may also be suitable as a therapeutic agent. Therefore, a method using the rare 34S sulfur isotope was developed and validated to distinguish exogenously administered sulfide from endogenous sulfide which is predominantly 32S‐sulfide. Sodium 34S‐sulfide was prepared and administered intravenously to Sprague Dawley rats. Concentrations of 32S and 34S‐sulfide were measured in blood and tissues after derivatization with monobromobimane as monobromobimane derivative, separation by reverse phase HPLC and quantification by mass spectroscopy. On intravenous infusion of sodium 34S‐sulfide into rats, blood sulfide concentrations of 34S‐sulfide, but not 32S‐sulfide increased in a dose‐dependent manner indicating that exogenously administered sulfide can be traced and distinguished from endogenous sulfide. The method will be useful in monitoring of the distribution of therapeutic sulfide in tissues and organs.

Hydrogen sulfide is best known as an environmental pollutant and human health hazard. Recently, sulfide has gained recognition as an endogenous biological mediator and is being examined for use as a therapeutic agent. As sulfide may be administered by both inhaled and parenteral routes, the question arises of how exposure to sulfide compares between the two modes of administration. Sprague Dawley rats were exposed for up to two hours of hydrogen sulfide gas up to 400 ppm or received up to 20 mg/kg sodium sulfide by continuous intravenous infusion. Sulfide concentrations in venous blood were quantified as sulfide dibimane derivative. Both modes of administration lead to a dose‐dependent elevation in blood sulfide concentrations over baseline concentrations and reached a new steady‐state concentration within two hours. Steady state blood sulfide concentrations show a simple linear relationship to hydrogen sulfide gas concentration or sodium sulfide dose. Identical blood sulfide concentrations can be achieved by either route of administration suggesting bioequivalency of hydrogen sulfide inhalation and sodium sulfide intravenous infusion in modulating blood sulfide concentrations. This suggests that both modes of administration may exert similar therapeutic effects.