Gas chromatography/selected ion monitoring mass spectrometric determination of captopril in human blood

Funke, Phillip T.; Ivashkiv, Eugene; Malley, Mary F.; Cohen, Allen I.

doi:10.1021/ac50057a021

Cited by 61 publications

(24 citation statements)

References 8 publications

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“…The initial development of a suitable assay procedure involved the use of antioxidants, chelating agents, and derivatising agents. The formation of a derivative of captopril with Nethylmaleimide (NEM) was used to stabilise captopril in blood and urine (Funke et al 1980). The captopril disulphide dimer metabolite was found to be stable in biological fluids and was unaffected by the addition of NEM.…”

Section: Assay Methodsmentioning

confidence: 99%

“…The first method used gasliquid chromatography/selected ion monitoring mass spectrometry (GC/MS) and involved the formation of a captopril-NEM derivative; following a chromatographic procedure, this derivative was methylated and measured as the methyl ester (Funke et al 1980). 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of unchanged captopril in blood was initially 16.5 p.gfL and was later improved to about 10 p.gfL (ER Squibb & Sons, unpublished data).…”

Section: Assay Methodsmentioning

confidence: 99%

See 1 more Smart Citation

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%

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 has been determined by several methods, including gas chromatography (GC) [2], gas chromatography-mass spectrometry (GC-MS) [3,4], highperformance liquid chromatography (HPLC) [5][6][7][8][9][10][11] and liquid chromatography-mass spectrometry (LC-MS) [12]. However, the GC method is limited by sensitivity and the GC-MS or LC-MS methods may not be widely accessible.…”

Section: Introductionmentioning

confidence: 99%

Simultaneous determination of captopril and hydrochlorothiazide in human plasma by reverse-phase HPLC from linear gradient elution

Huang

Yang

et al. 2006

Journal of Pharmaceutical and Biomedical Analysis

136

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“…It is the prototype of the thiazide group and antihypertensive drug. [3] Literature survey reveals that CAP was determined by several methods including spectrophotometric, [4][5][6][7][8] HPLC, [9][10][11] flow injection biamperometric, [12] flow injection chemiluminescence, [13] potentiometric and visual titrimetric, [14] and FT-Raman spectroscopy. [15] HZ was determined by capillary electrophoresis, [16] electrochemical study, [17] spectrophotometric, [18][19][20][21][22] and HPLC.…”

Section: Introductionmentioning

confidence: 99%

Simultaneous estimation of captopril and hydrochlorothiazide in combined dosage forms

Rao¹,

Panda²,

Keshar³

et al. 2012

Chron Young Sci

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Aim: This work deals with the simultaneous determination of captopril (CAP) and hydrochlorothiazide (HZ) in twocomponent solid dosage form, without prior separation, by three different techniques (simultaneous equation, absorbance ratio method, and first-order derivative method). Materials and Methods: This work was carried out on Shimadzu electron UV1800 double-beam UV-Visible spectrophotometer. The absorption spectra of reference and test solutions were carried out in 1 cm matched quartz cell over the range of 200-400 nm. Methanol and distilled water are used as solvent. Results: The first method is the application of simultaneous equation. Where the linearity ranges for both the drugs were 5-35 µg/ml. The second method is the determination of ratio of absorbance at 271 nm, the maximum absorption of HZ and isobestic wavelength 209 nm, the linearity ranges for both the drugs were 10-120 µg/ml The third method is the first-order derivative method, where the CAP shows wavelength at 222 nm and HZ shows at 340 nm, and the linearity ranges for CAP and HZ were 1-30 µg/ ml and 1-40 µg/ml, respectively. The proposed procedures were successfully applied for the simultaneous determination of both the drugs in commercial tablet preparation. The validity of the proposed methods was assessed by applying the standard addition technique where the percentage recovery of the added standard was found to be 99.52±0.214 and 99.00±0.165 using the simultaneous equation method, 99.76±0.684 and 99.58±0.279 using the graphical absorbance ratio method, and 99.45±0295 and 99.21±0.678 using first derivative method, for CAP and HZ, respectively. Conclusion: The proposed procedures are rapid, simple, require no preliminary separation steps, and can be used for routine analysis of both drugs in quality control laboratories.

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Gas chromatography/selected ion monitoring mass spectrometric determination of captopril in human blood

Cited by 61 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

Simultaneous determination of captopril and hydrochlorothiazide in human plasma by reverse-phase HPLC from linear gradient elution

Simultaneous estimation of captopril and hydrochlorothiazide in combined dosage forms

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