SIMULTANEOUS DETERMINATION OF A NOVEL ANTIARRHYTHMIC AGENT, 7-BENZYL-3-THIA-7-AZABICYCLO[3.3.1] NONANE AND ITS SULFOXIDATION METABOLITE IN PLASMA AND URINE BY HPLC

A HPLC method was developed for the simultaneous determination of the concentrations of 7-benzyl-3-thia-7-azabicyclo[3.3.1]nonane (I) as the hydrochloride and the corresponding sulfoxide (II), the major metabol ite, in dog plasma and urine. Plasma and urine samples were alkalinize d and extracted with chloroform. An aliquot was injected on to a HPLC system with a C6 reversed-phase column and an UV detector. Acetonitril e-methanol-37.5 mM phosphate buffer, pH 6.8 (28:28:44 v/v) containing 4.0 mM triethylamine was used as a mobile phase. The compounds I and I I were detected at 261 nm. The extraction recovery for I and II was 85 % and 94% from plasma and 89% and 91% from urine, respectively. Good l inearity (r>0.994) was observed throughout the range of 0.1-10.0 mu g/ ml for I and 0.04-10 mu g/ml for II in plasma and in urine. Intra- and inter-assay variabilities were less than 8%. The accuracy of this met hod was > 95% for both compounds, and the limits of quantitation were 0.08 mu g/ml for I and 0.03 mu g/ml for II in plasma, and in urine, re spectively. This method was applied to determine plasma and urine conc entrations of I and II simultaneously in a dog treated with I.