HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHIC ANALYSIS OF THE ANTITUBERCULOSIS DRUGS ACONIAZIDE AND ISONIAZID

Reversed-phase HPLC methods are described for determining the stabilit y and concentration certification of the antituberculosis prodrug acon iazide (ACON) in aqueous dosing solution and for assessing the concent rations of ACON and isoniazid (INH) in plasma from ACON-treated male a nd female Fischer-344 rats. ACON was analyzed in plasma by direct inje ction; it was separated on a 250 x 4.6 mm I.D. 5 mu m C-18 column usin g a 40% aqueous methanol mobile phase containing 5 g/l ammonium format e, and detected at 313 nm. INH was determined in the plasma of treated rats after a two-step precipitation of plasma proteins; it was separa ted on a 250 mm x 4.6 mm I.D. 5 pm CN column, eluted with 5% aqueous i sopropanol containing 5 g/l ammonium formate, and detected with an ele ctrochemical detector at +0.8 V. These methods allow a simple, rapid, and reliable determination of ACON and INH in plasma down to 0.1 mu g/ ml.