Simple determination of hydrochlorothiazide in human plasma and urine by high performance liquid chromatography

Allopurinol is converted almost completely into a single active metabolite, oxipurinol, which has the same therapeutic pattern but a much longer elimination half-life than the parent compound. Therefore both allopurinol and oxipurinol were evaluated in our bioequivalence study in healthy volunteers comparing two allopurinol brands. Bioequivalence determination was based on the 90% confidence intervals (CI) of the area under the plasma concentration time curve from time zero to infinity (AUC0-infinity), of the area from time zero to the last measurable plasma concentration (AUC0-t (last)), and Cmax. Because of the lack of compound-specific criteria we used conventional limits for the bioequivalence range. Under these conditions the brand chosen as test preparation was judged to be bioequivalent to the reference form with respect to the extent of bioavailability, AUC0-infinity, and AUC0-t (last) of the parent drug. The CI of Cmax of allopurinol slightly exceeded the upper limit of 130%, so that bioequivalence was not confirmed with regard to the rate of bioavailability of the parent compound. The CI values of both AUC and Cmax of the active metabolite were tighter than those of allopurinol. In addition, the CI values of Cmax of oxipurinol were smaller than those of the corresponding AUC. As a consequence the test drug can clearly be accepted as bioequivalent, based on metabolite data. Since the active metabolite is of greater therapeutic significance than the parent drug, assessment of the bioequivalence of allopurinol preparations needs to be based on oxipurinol rather than allopurinol.(ABSTRACT TRUNCATED AT 250 WORDS)

show abstract

“…The precision is 3-5%. The assay was validated by liquid chromatography with photodiode array detection [5].…”

Section: Analytical Techniquesmentioning

confidence: 99%

Bioequivalence of allopurinol preparations: to be assessed by the parent drug or the active metabolite?

et al. 1993

Self Cite

View full text Add to dashboard Cite

show abstract

“…The precision was 3 5%. The assay was validated by liquid chromatography with photodiode array detection [13]. Plasma uric acid was determined enzymatically using the Boehringer Mannheim test kit no.…”

Section: Materials and And Methodsmentioning

confidence: 99%

Disposition and uric acid lowering effect of oxipurinol: comparison of different oxipurinol formulations and allopurinol in healthy individuals

Walter‐Sack

Vries

et al. 1995

Eur J Clin Pharmacol

Self Cite

View full text Add to dashboard Cite

We have investigated the disposition and plasma uric acid lowering effect of oxipurinol in ten healthy individuals following oral administration of three different formulations of oxipurinol and of allopurinol in equimolar doses. The reduction of plasma uric acid was clearcut up to 48 h. As estimated from plasma AUC0-infinity, Cmax, tmax, tlag, and urinary drug excretion, a conventional rapid release preparation of oxipurinol sodium was clearly superior to oxipurinol as free acid and to enteric coated microtablets of oxipurinol sodium. Plasma oxipurinol concentrations following a single dose of the conventional formulation of oxipurinol sodium were approximately 25% lower than those observed after an equimolar dose (300 mg) of allopurinol, but mean Cmax reached the value reported to be necessary for 90% inhibition of xanthine oxidase. Since prolonged administration will result in accumulation of oxipurinol because of its slow elimination, this type of oxipurinol formulation can be expected to meet the therapeutic requirements for a drug to lower plasma uric acid.

show abstract

“…The influence of pH was considered important given the wide discrepancy of optimal pH values reported by other authors (9)(10)(11)(12)(13)(14)(15)(16)(17)(18). Samples of an aqueous solution of HCT were made in different buffers (phosphate, acetate, borate) having pH values of 3.8, 6, 7.5, 9 and extracted with ethyl acetate.…”

Section: Influence Of Ph On the L/l Extraction Process Of Hctmentioning

confidence: 99%

“…has been considered. Several such methods for HCT have been proposed in the literature (9)(10)(11)(12)(13)(14)(15)(16)(17)(18), but there are large differences between authors with respect to optimal conditions. In particular, specific conditions associated with the evaluation of the bioequivalence of products containing 25 mg HCT are poorly considered.…”

Section: Introductionmentioning

confidence: 99%

Liquid extraction and HPLC-DAD assay of hydrochlorothiazide from plasma for a bioequivalence study at the lowest therapeutic dose

Medvedovici

Mircioiu

David

et al. 2000

Eur. J. Drug Metab. Pharmacokinet.

View full text Add to dashboard Cite

The main parameters considered in optimizing the liquid extraction and quantitative assay were the yield, precision, limit of quantification, time required for extraction and concentration, and quantity of solvent. The influence on these parameters of the following factors was examined: nature of the extracting solvent, quantity of solvent, co-extraction solvent, and duration of stirring. Instead of equilibrium parameters of the involved thermodynamic system, a kinetic approach was preferred in terms of the effective partition 'constant', which is not really constant but a function of time and extraction conditions. The final selected method, considered to be rapid and simple, was applied to determine the pharmacokinetics of hydrochlorotiazide (HCT) after administration of Capozide (Bristol-Myers Squibb) tablets containing 50 mg Captopril and 25 mg HCT, to 4 healthy volunteers. The results obtained were in accordance with the pharmacokinetic parameters of HCT reported in the literature.

show abstract

Simple determination of hydrochlorothiazide in human plasma and urine by high performance liquid chromatography

Cited by 25 publications

References 17 publications

Bioequivalence of allopurinol preparations: to be assessed by the parent drug or the active metabolite?

Bioequivalence of allopurinol preparations: to be assessed by the parent drug or the active metabolite?

Disposition and uric acid lowering effect of oxipurinol: comparison of different oxipurinol formulations and allopurinol in healthy individuals

Liquid extraction and HPLC-DAD assay of hydrochlorothiazide from plasma for a bioequivalence study at the lowest therapeutic dose

Contact Info

Product

Resources

About