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

Abstract

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.