GLC determination of a novel polyvalent saluretic agent, (6,7-dichloro-2-methyl-1-oxo-2-phenyl-5-indanyloxy)acetic acid, in biological fluids.

Highly specific and sensitive GLC methods were developed for the determination of (6,7-dichloro-2-methyl-1-oxo-2-phenyl-5-indanyloxy)acetic acid, a novel saluretic-uricosuric agent, in biological fluids. The procedures involve the addition of an internal standard, (6,7-dichloro-2-cyclopentyl-2-methyl-1-oxo-5-indanyloxy)acetic acid, to the biological specimens followed by extraction of the acids into benzene at pH 1. The indanones are back-extracted into sodium hydroxide and reextracted into methylene chloride under acidic conditions. The acids are subsequently converted to the methyl esters for GLC analysis by reaction with diazomethane. The sensitivity of the method is such that 1.0 microgram of material/ml of plasma can be analyzed using a flame-ionization detector. When the derivatized samples are analyzed using a 63Ni-electron-capture detector, the sensitivity is such that 2.5 ng of compound can be detected. These levels are suitable for the analysis of samples obtained following a therapeutic dose. A recovery of 98.8 +/- 11.9% was obtained using the electron-capture method for plasma (n = 322). Recoveries using flame ionization were 99.1 +/- 4.4% (plasma, n = 207) and 99.8 +/- 4.9% (urine, n = 163). Quantitation of the major ring-hydroxylated metabolite (in chimpanzee and human) was accomplished following silylation of the methyl esters.