High-performance liquid chromatographic determination of furosemide in plasma and urine and its use in bioavailability studies (original) (raw)
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Comparative bioavailability of two furosemide formulations in humans
Journal of Pharmaceutical Sciences, 1984
Twelve healthy male volunteers participated in a balanced crossover comparison of a brand-name and generic furosemide formulations. Each treatment was given as a single 40-mg tablet following an overnight fast. Furosemide concentrations in plasma and urine were determined up to 24 h after treatment; urine output and urinary sodium excretion were also measured. In comparison with the brand-name tablets, generic furosemide was significantly less bioavailable. Using a 95% confidence interval approach, generic furosemide gave up to 66% lower maximum furosemide plasma levels, up to 52% less area under the plasma level curve to infinite time, and up to 37% less urinary recovery of furosemide. Comparison of the effect of the two treatments was a less sensitive measurement of bioequivalence. Confidence intervals for differeences in urinary output and sodium excretion over the period of maximum effect (0–4 h) were, however, asymmetrical, and pharmacodynamic differences between treatments were significant at the 10% level.
Determination of Furosemide in Whole Blood using SPE and GC-EI-MS
Journal of Analytical Toxicology, 2005
A simple and rapid method was validated to determine furosemide in whole blood. The experimental work was performed so that all validation parameters are considered simultaneously in a one-day assay protocol. A solid-phase extraction procedure using BondElut| Certify columns was used to extract this compound from blood samples, while ketoprofen was used as an internal standard. The extracts were analyzed by gas chromatography-electron ionization-mass spectrometry after on-column derivatization with trimethylanilinium hydroxide (0.2M in methanol). Calibration curves were prepared daily, between 0.10 and 5.00 pg/mL, and the correlation coefficients were above 0.9910. The calculated limits of detection and quantitation were 0.010 and 0.045 pg/mL, respectively. Control samples at low, medium, and high concentrations (0.30, 0.75, and 3.00 pg/mL) of furosemide of an independent source were measured in the same day. Precision and trueness, calculated in terms of relative standard deviation (%), were less than 15% for all concentration levels. The relative recoveries calculated for the three levels of the control samples were 104%, 89%, and 91%, respectively. In general, a sensitive, specific, and reliable procedure has been developed for the determination of furosemide in whole blood samples and was found suitable for the application in postmortem forensic toxicology routine analysis.
ANALYTICAL DETERMINATION OF FUROSEMIDE: THE LAST RESEARCHES
Furosemide (FUR) is an anthranilic acid derivative which is a potent diuretic widely used in the treatment of congestive heart failure and edema. FUR works by blocking the absorption of salt and fluid in the kidney tubules, causing a profound increase in urine output (diuresis). Due to the considerable use of FUR, analytical determination is frequent. In this manuscript, a review of the methods developed for determination of FUR from the year 2008 is presented.
Journal of Chromatography B: Biomedical Sciences and Applications, 1991
Furosemide (FD; Lasix®) is a loop diuretic which strongly increases both urine flow and electrolyte urinary excretion. Healthy volunteers were administered 40 mg orally (dissolved in water) and concentrations of FD were determined in serum and urine for up to 6 h for eight subjects, who absorbed water at a rate of 400 ml/h. Quantification was performed by HPLC with fluorescence detection (excitation at 233 nm, emission at 389 nm) with a limit of detection of 5 ng/ml for a 300-μl sample. The elution of FD was completed within 4 min using a gradient of acetonitrile concentration rising from 30 to 50% in 0.08 M phosphoric acid. The delay to the peak serum concentration ranged from 60 to 120 min. FD was still easily measurable in the sera from all subjects 6 h after administration. In urine, the excretion rates reached their maximum between 1 and 3 h. The total amount of FD excreted in the urine averaged 11.2 mg (range 7.6–14.0 mg), with a mean urine volume of 3024 ml (range 2620–3596 ml). Moreover, the urine density was lower than 1.010 (recommended as an upper limit in doping analyses to screen diuretics) only for 2 h. An additional volunteer was administered 40 mg of FD and his urine was collected over a longer period. FD was still detectable 48 h after intake. Gas chromatography—mass spectrometry with different types of ionization was used to confirm the occurrence of FD after permethylation of the extract. Negative-ion chemical ionization, with ammonia as reactant gas, was found to be the most sensitive method of detection.
Journal of Chromatography B, 2002
Furosemide, a drug that promotes urine excretion, is used in the pharmacotherapy of various diseases and is considered as a doping agent in sports. Using alkaline electrolytes, analysis of furosemide by dodecyl sulfate based micellar electrokinetic capillary chromatography (MECC) and capillary zone electrophoresis (CZE) with laser-induced fluorescence detection (LIF, analyte excitation with the 325 nm line of a HeCd laser) is described. Data produced by injection of plain or diluted patient urines are confirmed with those obtained via analysis of urinary solid-phase extracts. CZE-LIF and MECC-LIF are thereby shown to permit unambiguous recognition of furosemide in urines collected after ingestion of therapeutic doses of this drug. This is in contrast to solute detection via UV absorbance for which the extraction of furosemide is required. MECC based electropherograms are somewhat more complex compared to those obtained by CZE-LIF, this suggesting that the latter approach is more suitable for rapid screening of urines with direct sample injection and LIF detection. Alternatively, 2 capillary electrophoresis with negative electrospray ionization-ion-trap tandem mass spectrometry (CE-MS ) is shown to permit the direct confirmation of furosemide in human urine. This approach is based upon the monitoring of the m /z 2 329.3→m /z 285.2 precursor-product ion transition. CZE-LIF and CE-MS with injection of plain or diluted urine represent simple, rapid and attractive urinary screening and confirmation assays for furosemide in patient urines.
Acta Pharmacologica et Toxicologica, 1974
A modification of the HAJDU & HAUSSLER method (1964) for the determination of furosemide is described. The sensitivity is lo? 2 ng/ml. The binding of furosemide to plasma proteins is determined in vitro at room temperature by an ultrafiltration method. At concentrations between 10 and 400 pg/ml, 99-95 % was bound in normal plasma. In therapeutically dialysed plasma from surgical patients with acute renal failure the binding was reduced by 9-14%. The number of yg of drug bound per mg albumin was also significantly reduced in the patient plasma. A ''ka,.l value" for the range l(r100 pg/ml was approximately 3 X lo5 in donor plasma and 2 X lo4 in patient plasma. A ''kavZ value" (100-400 pg/ml) was 3X 104 in donors and 8 X lo3 in patients. The kavl and kpve values were significantly lower in patient plasma than in donor plasma and also lower in patient plasma than in Ringer solutions to which albumin had been added.
Biopharmaceutics & Drug Disposition, 1988
Furosemide tablets, with markedly different dissolution characteristics, and solution were orally administered to 21 healthy adult males to determine the effect of in vitro dissolution rate on in vivo bioavailability profiles. Furosemide 40 mg was given as Tablet A (fast dissolution characteristics), Tablet B (slow dissolution characteristics), and an aqueous solution. Both batches of tablets had identical formulae and were produced by a common process. The dissolution rate of the slower Tablet B was probably retarded by extension of the wet granulation time. Blood was collected for 12 h postdose and urine for 24 h. Peak plasma furosemide concentrations after the solution were significantly greater than after the tablets; there was no significant difference between the tablets. The time to peak occurred significantly earlier with the solution, with no significant difference between the tablets. Relative bioavailabilities of Tablet A and B were 89 per cent and 101 per cent, respectively, as determined by AUC, and 79 per cent and 84 per cent, respectively, as determined by urine recovery. These differences are not statistically significant. These results indicate that dissolution rate profiles of furosemide tablets may not be predictive of in vivo bioavailability.
RP-HPLC Method for Estimation of Furosemide in Rabbit Plasma Revathi Mannam
2018
The present RP-HPLC method for in vivo estimation of furosemide in male rabbits was developed to improve its efficiency. The method was developed as per ICH guidelines. ODS column (C18 250 × 4.6 mm, 5 μm) with flow rate 1 mL/min was used and the column temperature was set at 25°C. The runtime was set for 10 min and the detection was done at λmax 210 nm. The mobile phase used was phosphate buffer (pH 4.6) and acetonitrile in 30:70 ratio. The developed method had shown high specificity for furosemide in rabbit plasma and the regression was found to be R 2 =0.9999 in the range of 0.1 to 5 μg/0.5 mL. The regression equation was found to be Y=0.4818X+0.0039. The lower limit of detection was found to be 0.1 μg/0.5 mL of plasma. The developed method for furosemide in rabbit plasma had shown good accuracy without any intraday and inter-day variation. The proposed method was found to be adequate and reproducible for the estimation of furosemide in rabbit plasma.
Journal of pharmaceutical sciences, 1976
35S-Furosemide was administered to beagle dogs and rhesus monkeys in an oral solution on a single and a 20 repeated 5-mg/kg/day dosing regimen. Following the single dose, 25.0% (dogs) and 24.0% (monkeys) of the dose were excreted in the urine in 24 hr. TLC analysis demonstrated that both species had similar excretory patterns; i.e., over 80% of the amount excreted in the urine was present as unchanged durosemide and the remainder was composed of a known metabolite, saluamine, and an as yet unidentified metabolite(s). The repetitive dosing regimen did not appear to alter significantly either the total amount recovered in the 24-hr urine or the excretion pattern. Studies in dogs showed that only 50-60% of furosemide was absorbed from oral solution. A significant biliary secretion elimination pathway for furosemide also was observed.