DIRECT GRADIENT REVERSED-PHASE HPLC ANALYSIS AND PRELIMINARY PHARMACOKINETICS OF NALIDIXIC-ACID, 7-HYDROXYMETHYLNALIDIXIC ACID, 7-CARBOXYNALIDIXIC ACID, AND THEIR CORRESPONDING GLUCURONIDE CONJUGATES IN HUMANS

A gradient reversed-phase high pressure liquid chromatographic analysi s was developed for the direct measurement of nalidixic acid with its acyl glucuronide, 7-hydroxymethylnalidixic acid with its acyl and ethe r glucuronides, and 7-carboxynalidixic acid in human plasma and urine. The glucuronides and 7-carboxynalidixic acid were not present in plas ma after an oral dose of 1,000 mg nalidixic acid. The acyl glucuronide s of 7-carboxynalidixic acid were not present in plasma and urine. The acyl glucuronides are stable in urine at pH 5.0-5.5. The subject's ur ine must therefore be acidified by the oral intake of 4 x 1 g of ammon ium chloride per day. With acidic urine, hardly any nalidixic acid was excreted unchanged (0.2%). It was excreted as acyl glucuronide (53.4 % of dose), 7-hydroxymethylnalidixic acid (10.0%), the latter's acyl g lucuronide (30.9%), and 7-carboxynalidixic acid (4.2%).