Determination of Captopril in Human Blood and Urine by GLC-Selected Ion Monitoring Mass Spectrometry after Oral Coadministration with Its Isotopomer

Cohenx, Allen I.; Devlin, Richard G.; Ivashkiv, Eugene; Funke, Phillip T.; McCormick, Terrence

doi:10.1002/jps.2600711117

Cited by 37 publications

(7 citation statements)

References 17 publications

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“…The lower limit of quantitation of unchanged captopril in blood was initially 16.5 p.gfL and was later improved to about 10 p.gfL (ER Squibb & Sons, unpublished data). 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).…”

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

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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)

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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

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“…The response of the control sample was used to correct the data for differences in response from the calibration slope as described previously. 6 The standard curve for captopril was constructed by plotting area ratios of the analyte 7 to the internal standard 9 versus the amount ratios of 1 and 4, the amount being the total nanograms of 1 and 4 in each calibration standard. The standard curve for S-benzoyl captopril was similarly constructed by using the areas of 8 and 10 and the amounts of 3 and 6.…”

Section: Methodsmentioning

confidence: 99%

Simultaneous determination of captopril and S-benzoyl captopril in human blood by capillary gas chromatography-mass selective detection

Jemal

Ivashkiv

Cohen

1985

Biol. Mass Spectrom.

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Using a new table-top electron-impact mass selective detector, interfaced with a narrow bore, fused silica capillary gas chromatograph, a method has been developed for the simultaneous determination of captopril and S-benzoyl captopril. With a capillary column the two components could be chromatographically resolved, thus permitting the use of electron-impact ionization for quantitative measurements.

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“…Structures of Captopril and Related Compounds (Figure 1)" "Key: C6H8N02, IV-ethylsuccinimide, NES; C7H60, benzoyl; C6H5S, phenylthio; C2H30, acetyl. methyl ester by selected ion monitoring GC/MS (8)(9)(10).…”

Section: Literature Citedmentioning

confidence: 99%

N-Ethylmaleimide as a new electrophoric derivatizing reagent for the gas chromatography of thiols

Jemal¹,

Cohen²

1985

Anal. Chem.

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Determination of Captopril in Human Blood and Urine by GLC-Selected Ion Monitoring Mass Spectrometry after Oral Coadministration with Its Isotopomer

Cited by 37 publications

References 17 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

Simultaneous determination of captopril and S-benzoyl captopril in human blood by capillary gas chromatography-mass selective detection

N-Ethylmaleimide as a new electrophoric derivatizing reagent for the gas chromatography of thiols

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