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Torsemide is a new diuretic drug with a profile of action similar to that of furosemide. The high potency of torsemide results in low dose therapy and causes problems for the pharmacokinetic study of the drug due to low plasma levels. Described here are methods for the analysis of torsemide and two metabolites in plasma and urine using solid-phase extraction and liquid chromatography. The limits of quantitation are 10 ng/mL for plasma and 20 ng/mL for urine. The relative standard deviations for precision are less than 10% for most analytes at most concentrations in the calibration range. The recoveries from plasma were 94.3, 92.9, and 95.6%, and from urine were 77.5, 66.6, and 76.5% for torsemide and metabolites M1 and M5, respectively. The method was suitable for pharmacokinetic studies. Data from a normal volunteer are presented.

A method for the measurement of a potential diuretic-antihypertensive agent, (+/-)-[[6,7-dichloro-2-(4-fluorophenyl)-2-methyl-1-oxo-5-indanyl] oxy]acetic acid, in biological fluids is described. The procedure involves the addition of a related internal standard to the specimens followed by extraction of the acids into toluene at pH 1. The indanyloxyacetic acids, following back-extraction into base and reextraction into methylene chloride at an acidic pH, are converted to methyl esters by reaction with ethereal diazomethane for subsequent gas chromatographic analysis. The sensitivity of the method is such that 5 ng of drug in 1 mL of biological specimen can be quantitated using a 63Ni electron-capture detector. The recovery from plasma in the 5-2000-ng/mL range (n = 53) was 97.0 +/- 16.3%. Differences were noted in the disposition of the enantiomers of this agent in dogs following a pharmacologically active dose.

A sensitive GLC assay for ticrynafen, a diuretic agent with uricosuric properties, and its two metabolites in urine, serum, and plasma is described. The method employs methylation of carboxylic acid groups and trimethylsilyation of the hydroxyl group on one metabolite that cannot otherwise be separated readily from ticrynafen as a simple methyl ester. Urinary output and serum or plasma levels of ticrynafen and its two metabolites were measured in specimens from human volunteers receiving one 250-mg tablet.

A sensitive fluorescence method for the determination of indapamide was developed. Reaction of indapamide with sodium hydroxide at 100 degrees yielded a fluorescent product, and addition of formaldehyde to the fluorescent product increased its fluorescence intensity by a factor of three. The assay is sensitive to levels of indapamide of 0.025 microgram/ml in an aqueous solution, and a linear response between 0.025 and 2.0 microgram/ml was observed. The procedure was adapted to the analysis of intact indapamide in urine. Concentrations of indapamide of 0.05 microgram/ml can be detected in dogs given 20 mg of the drug.