Liquid chromatographic determination of guanethidine salts and hydrochlorothiazide using electrochemical detection and ion-pair techniques.

A high-performance liquid chromatographic method with amperometric detection utilizing oxidation at the glassy carbon electrode is reported for the quantitative determination of a guanethidine (1)-hydrochlorothiazide (2) mixture. The drug mix is difficult to analyze by a single assay procedure due to large differences in the chemistry and chemical structure of the compounds. The drugs are best separated on an octadecylsilane column using 30:70 acetonitrile:0.05 M aqueous sodium dihydrogen phosphate containing 0.02 M sodium pentanesulfonate (pH 2.5) as the mobile phase at a 1.0 mL/min flow rate. Using a cell potential of +1300 mV versus Ag/AgCl and procaine hydrochloride as the internal standard, calibration curves were established for 1 monosulfate or sulfate and 2 in the 0.5-10 and 1.25-25 micrograms/mL range, respectively. Accuracy and precision of the assay are in the 1.7-6% range. The procedure is shown applicable to the analysis of a combination dosage form and is also useful for either drug in a single component dosage form.