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

✍ Scribed by Toshikazu Yamaguchi; Mie Miyamoto; Yuzo Utsui; Yutaka Sekine; Masahisa Hashimoto

• Book ID: 104143878
• Publisher: Elsevier Science
• Year: 1978
• Tongue: English
• Weight: 578 KB
• Volume: 160
• Category: Article
• ISSN: 1873-3778
• DOI: 10.1016/s0021-9673(00)91794-1

✦ Synopsis

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 mixturesj. The N-oxide is then pyrolyzed to Zmethyl 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_ GC was carried out using a JEOL Model JGC-20KE gas chromatograph equipped with a IO-mCi 63Ni electron-capture detector. A silanized glass cohrmn (200 cm X 2 mm I.D.) was packed with 2% QF-1 on .Gas-Chrom Q (80-100 mesh).