Reference

Determination of captopril and its mixed disulfides in plasma and urine by high-performance liquid chromatography

Determination of captopril and its mixed disulfides in plasma and urine by high-performance liquid chromatography. Hayashi, Kouji; Miyamoto, Mike; Sekine, Yutaka (Res. Lab., Dainippon Pharm. Co., Ltd., Osaka 564, Japan). J. Chromatogr., 338(1), 161-9 (English) 1985. CODEN: JOCRAM. ISSN: 0021-9673. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) A HPLC method was developed which enables sensitive detn. of captopril [62571-86-2] and its mixed disulfides in plasma and urine after oral administration of a new antihypertensive agent, 1-(D-3-acetylthio-2-methylpropanoyl)-L-prolyl-L-phenylalanine (DU-1219)(I) [74258-86-9]. Captopril is derivatized with N-(4-benzoylphenyl)maleimide [92944-71-3] and the deriv. [95791-35-8] is extd. with CHCl3 and assayed using a liq. chromatograph equipped with a UV detector at 254 nm. Mixed disulfides of captopril with thiol compds. such as cysteine, glutathione, and plasma proteins are reduced with PBu3 to form captopril, followed by derivatization with N-(4-benzoylphenyl)maleimide. Accurate detns. are possible over a captopril concn. range of 10-500 ng/mL in plasma and 100-2500 ng/mL in urine. The coeffs. of variation of captopril in plasma (200 ng/mL) and urine (500 ng/mL) are 3.7% and 2.6%, resp., and those of mixed disulfides of captopril are similar to those of captopril. Plasma levels and urinary excretion of captopril and its mixed disulfides in healthy volunteers following single oral administration of I (50 mg) were also detd.

Effects of a new angiotensin-converting enzyme inhibitor, 1-(D-3-acetylthio-2-methylpropanoyl)-L-propyl-L-phenylalanine [DU-1219], in normal men

Effects of a new angiotensin-converting enzyme inhibitor, 1-(D-3-acetylthio-2-methylpropanoyl)-L-propyl-L-phenylalanine [DU-1219], in normal men. Kono, Tsuyoshi (Sch. Med., Kyoto Univ., Kyoto 606, Japan). Naika Hokan, 30(12), 415-21 (English) 1983. CODEN: NAHOAI. ISSN: 0021-4809. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) The effects of DU-1219 (I) [74258-86-9] a new angiotensin-converting enzyme [9015-82-1] inhibitor, were studied in normal men. Systolic blood pressure fell 2-4 h after I and diastolic blood pressure fell 1-3 h and 12 h after the drug. Plasma angiotensin I (AI) [9041-90-1] increased 1-6 h after I and plasma renin [9015-94-5] activity (PRA) increased 2-6 h after the drug. Plasma aldosterone (PA) [52-39-1] decreased 1-12 h after I. Immediately after I followed by AI infusion, the blood pressure rose and PA increased. Then the blood pressure and PA began to decrease and the plasma AI and PRA began to increase; the onset of the blood pressure fall occurred 15-62 min later. The max. effects were obsd. 2 h after I. Then these inhibitory effects on the AI action were attenuated but still remained 6 (for plasma AI, PRA and PA) or 12 h (for blood pressure) after I. Systolic blood pressure 2-4 h after I and diastolic blood pressure 2-6 h after I were not significantly different from the pretreatment levels. When I is given orally it is converted to several metabolites including captopril [62571-86-2], which inhibits the converting enzyme. Therefore, I may be very useful clin. for the treatment of hypertension.