Determination of 7-chloro-3-(4-methyl-1-piperazinyl)-4h-1,2,4-benzothiadiazine-1,1-dioxide (DU-717) in plasma using electron-capture gas chromatography

A gas chromatographic method has been developed which enables accurate determination of a new antihypertensive agent, DU-717, in plasma. DU-717 is first extracted with ethyl acetate and, after a clean-up procedure, derivatized with peracetic acid followed by diazomethane to form 2-methyl DU-717 N-oxide (direct methylation leads to mixtures). The N-oxide is then pyrolyzed to 2-methyl DU-717 on a gas chromatograph equipped with electron-capture detection. Accurate determinations are possible over a concentration range from 10 to 150 ng/ml of DU-717 in plasma at a relative standard deviation of 6.2%. The minimum detectable concentration is 1 ng/ml. Plasma levels of DU-717 in spontaneously hypertensive and normotensive rats following single oral administrations (10 mg/kg) have also been determined.