Determination of captopril and its disulphide in biological fluids

Matsuki, Yasuhiko; Ito, Tomiharu; Fukuhara, Katsuharu; Nakamura, Tetsuya; Kimura, Michiko; Ono, Hiroshi; Nambara, Toshio

doi:10.1016/s0021-9673(00)82016-6

Cited by 20 publications

(3 citation statements)

References 8 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Cohen et al (1982) reported that a modified electron-impact gas-liquid chromatography-selected ion monitoring mass spectrometric method could also be used for analysis of captopril. The captopril-NEM derivative can also be converted to a hexafluoropropanyl ester instead of the methyl ester, which is followed by gas-chromatography with detection by electron capture (Bathala et al 1984), flame photometry (Matsuki et al 1980), a nitrogensensitive detector (Mantyla et al 1984), or selected-ion monitoring (Drummer et al I 984b;Matsuki et al 1982). The lower limits of quantitation of captopril and its disulphide metabolites by gas chromatography-electron capture are comparable to those for GC/MS, whereas the limit of sensitivity of gas chromatography-flame photometry is only in the milligram per litre range, which is not sufficiently sensitive for human blood concentration studies.…”

Section: Assay Methodsmentioning

confidence: 99%

Pharmacokinetics of Captopril in Healthy Subjects and in Patients with Cardiovascular Diseases

Duchin

McKinstry

Cohen

et al. 1988

Clinical Pharmacokinetics

130

View full text Add to dashboard Cite

Captopril, the first orally active inhibitor of angiotensin-converting enzyme, is used widely in the treatment of hypertension and congestive heart failure. The pharmacokinetics of this agent have been studied extensively in healthy subjects and in patients with hypertension, congestive heart failure, and chronic renal failure. Captopril contains a sulphydryl group and binds readily to albumin and other plasma proteins. The drug also forms mixed disulphides with endogenous thiol-containing compounds (cysteine, glutathione), as well as the disulphide dimer of the parent compound. These components in blood and urine are measured collectively as total captopril. Because of the reversibility of the formation of these inactive disulphides, total captopril may serve as a reservoir of the pharmacologically active moiety, and thus contribute to a duration of action longer than that predicted by blood concentrations of unchanged captopril. To measure free or unchanged captopril concentrations, a chemical stabiliser must be added to the biological samples to prevent the formation of captopril disulphides ex vivo. In healthy subjects given captopril intravenously, the body clearance of captopril and steady-state volume of distribution were about 0.7 L/h/kg and 0.8 L/kg, respectively. The elimination half-life of unchanged captopril was approximately 2 hours. The primary route of elimination of captopril is the kidney. The renal clearance of unchanged captopril exceeds the glomerular filtration rate, due to active tubular secretion of the drug. In healthy subjects, about 70 to 75% of an oral dose is absorbed and the bioavailability of captopril is approximately 65%. Peak blood concentrations are reached about 45 to 60 minutes after oral administration. The bioavailability of captopril is not altered by age or concomitant medications including diuretics, procainamide, allopurinol, cimetidine or digoxin. However, the co-administration of food or antacids, or probenecid with captopril has been shown to diminish the bioavailability of the latter and decrease its clearance, respectively. The decreased bioavailability of captopril when taken with meals does not significantly alter clinical responses to the drug. Over a wide range of oral (10 to 150 mg) and intravenous doses (2.5 to 10 mg) captopril had linear kinetics in healthy volunteers. In healthy subjects with normal renal function and patients with congestive heart failure given captopril 3 times daily, blood concentrations of total captopril accumulated, whereas those of unchanged captopril did not. Severe renal insufficiency was associated with an accumulation of both unchanged and total captopril.(ABSTRACT TRUNCATED AT 400 WORDS)

show abstract

Section: Assay Methodsmentioning

confidence: 99%

Pharmacokinetics of Captopril in Healthy Subjects and in Patients with Cardiovascular Diseases

Duchin

McKinstry

Cohen

et al. 1988

Clinical Pharmacokinetics

130

View full text Add to dashboard Cite

show abstract

“…It also reduces oxidative stress-induced cataract formation (Bhuyan et al, 1992). As a result of its extensive use, many different methods have been reported for captopril quantitation, including gas chromatography (Matsuki et al, 1982), gas chromatographymass spectrometry (Ito et al, 1987), and radioimmunoassay (Wong et al, 1981). HPLC has been used lately to monitor captopril levels in biological samples.…”

Section: Results Of Biological Sample Analysismentioning

confidence: 99%

Determination of captopril in biological samples by high‐performance liquid chromatography with ThioGlo™3 derivatization

Aykin

Neal

Yusof

et al. 2001

Biomedical Chromatography

View full text Add to dashboard Cite

Captopril, a well-known angiotensin converting enzyme (ACE) inhibitor, is widely used for treatment of arterial hypertension. Recent studies suggest that it may also act as a scavenger of free radicals because of its thiol group. Therefore, the present study describes a rapid, sensitive and relatively simple method for the detection of captopril in biological tissues with reverse-phase HPLC. Captopril was first derivatized with ThioGlo 3 [3H-Naphto[2,1-b]pyran,9-acetoxy-2-(4-(2,5-dihydro-2,5-dioxo-1H-pyrrol-1-yl)phenyl-3-oxo-)]. It was then detected by fluorescence-HPLC using an Astec C(18) column as the stationary phase and a water:acetonitrile:acetic acid:phosphoric acid mixture (50:50; 1 mL/L acids) as the mobile phase (excitation wavelength, 365 nm; emission wavelength, 445 nm). The calibration curve for captopril was linear over a range of 10-2500 nM and the coefficient of variation acquired for the within- and between-run precision for captopril was 0.5 and 3.8%, respectively. The detection limit of captopril with this method was found to be 200 fmol/20 microL injection volume. Its relative recovery from biological samples was determined to the range from 93.3 to 105.3%. Based on these results, we believe that our method is advantageous for captopril determination.

show abstract

“…Moreover, the presence of an angiotensin-converting enzyme without kininase activity was reported (9). However, as an alternative explanation, the participation of the metabolite of captopril is worth considering in the effect of this agent because captopril was reported to be rather unstable in biological fluid and to convert immediately into SQ 14,551 after oral administration in dogs (10). The observation in the present study that the attenuation of angiotensin I by SQ 14,551 was weaker than the augmentation of the effect of bradykinin by this agent enables us to deduce a hypothesis that the metabolite participates in a different effect of captopril on the time course between at tenuation of the effect of angiotensin I and the augmentation of the effect of bradykinin.…”

mentioning

confidence: 99%

Potentiation of bradykinin-induced decrease of blood pressure in dogs by SQ 14,551, the disulfide metabolite of Captopril.

1982

Self Cite

View full text Add to dashboard Cite

Captopril (D 3 mercapto 2 methyl propanoyl-L-proline, SQ 14,225 (mol. wt. 217.28)) is an orally active inhibitor of angiotensin-converting enzyme (1), and this agent attenuates the pressor effect of angiotensin I and augments the depressor effect of bradykinin in animals (2). It is well known that the conversion of angiotensin I to angiotensin II and the degradation of bradykinin are achieved with the same enzyme, angiotensin-converting enzyme or kininase II (3). In spite of the molecular identity of these two enzymatic moieties, we observed a difference in time course of in hibition by captopril between these two activities; longer-lasting augmentation of the depressor effect of bradykinin than the attenuation of the pressor effect of angiotensin i n vivo. Wong and Dreyfuss (4) reported that captopril was quickly converted into the disulfide in biological fluid, and Ikeda et al.(5) reported that the disulfide was the major urinary metabolite in rats and dogs. We observed the inhibiting effect of the disulfide metabolite (dimer) of captopril, SQ 14,551 (mol. wt. 432.54), on the angiotensin converting enzyme (kininase II) in dogs and compared it with that of captopril.The time course for the effect of captopril was determined by the blood pressure effects of angiotensin I and bradykinin in 5 female conscious beagle dogs weighing 10 to 13 kg. Each of the dogs was previously implanted with polyethylene cannulae, one at the femoral artery for measuring arterial pressure and the other at the femoral vein for intra venous administration of drugs, respectively; the other ends of the cannulae were exposed through the skin at the interscapular area. Arterial pressure was measured using a pressure transducer (Statham, P23Db) while the animals were quietly recumbent without any restriction. The pressor and depressor potencies of each 0

show abstract

Determination of captopril and its disulphide in biological fluids

Cited by 20 publications

References 8 publications

Pharmacokinetics of Captopril in Healthy Subjects and in Patients with Cardiovascular Diseases

Pharmacokinetics of Captopril in Healthy Subjects and in Patients with Cardiovascular Diseases

Determination of captopril in biological samples by high‐performance liquid chromatography with ThioGlo™3 derivatization

Potentiation of bradykinin-induced decrease of blood pressure in dogs by SQ 14,551, the disulfide metabolite of Captopril.

Contact Info

Product

Resources

About