THE MINIMAL METABOLISM OF INHALED 1,1,1,2-TETRAFLUOROETHANE TO TRIFLUOROACETIC-ACID IN MAN AS DETERMINED BY HIGH-SENSITIVITY F-19 NUCLEAR-MAGNETIC-RESONANCE SPECTROSCOPY OF URINE SAMPLES

In this work, oxidative metabolism of the new propellant, 1,1,1,2-tetr afluoroethane to trifluoroacetic acid in man is shown to be minimal. A lternative propellants and refrigerants are under development to repla ce the currently used chlorofluorocarbons which lead to stratospheric ozone depletion. One potentially useful replacement is the hydrofluoro carbon, 1,1,1,2-tetrafluoroethane (HFA 134a). Before it can be used, h owever, particularly as a propellant in an aerosol pharmaceutical form ulation whereby the compound is in effect dosed to people, it is impor tant that the safety of this compound is established. As a part of thi s safety evaluation it is necessary to understand the metabolism of HF A-134a. In this work the production of the potential oxidative metabol ite of HFA-134a, trifluoroacetic acid (TFA)has been studied in human u rine following inhalation dosing with HFA-134a. The concentrations of TFA in urine have been measured using a highly sensitive F-19 nuclear magnetic resonance procedure with a limit of detection of 10 ng ml(-1) based on an acquisition time of only 2.25 h per sample. TFA is the on ly fluorinated species observed in the urine samples and only at very low levels, indicating that the oxidative route of metabolism can occu r in vivo in man, but this metabolism is minimal in terms of percentag e of administered dose.