Methaqualone metabolites in human urine after therapeutic doses.

We measured five principal metabolites of methaqualone in the urine of seven volunteers after single and multiple doses of the drug. Urine, collected for up to 72 hours after the last dose, was analyzed for methaqualone and its principal metabolites by high-resolution capillary-column gas chromatography. The major biotransformation of methaqualone under therapeutic conditions occurred through benzylic and para-hydroxylation of the o-tolyl moiety. Methaqualone itself was present in concentrations of no more than 1 mg/liter, if it could be detected at all. The observed physiological effects ant total urinary excretion of metabolites reflected the cumulative nature of the parent drug when it was administered in multiple doses. No clear relationship was found between appearance of a specific metabolite and time after ingestion of the drug, although higher amounts of 2-methyl-3-(2'-hydroxymethylphenyl)-4(3H)-quinazolinone were noted in those individuals who tolerated the drug less well.

Radioimmunoassay of methaqualone and its monohydroxy metabolites in urine.

A commercial radioimmunoassay kit was evaluated for efficacy in detecting methaqualone or its metabolites in urine of persons receiving this drug. The drug and its unconjugated 3'- and 4'-monohydroxy metabolites could be detected equally well. The unconjugated alpha-monohydroxy metabolite was about 80% as reactive and the unconjugated 6-monohydroxy metabolite reacted only very weakly. Quantitation of the conjugated metabolites was less sensitive than of unconjugated. Nineteen urine specimens which reacted positively to radioimmunoassay and which thin-layer chromatography had shown to contain methaqualone and its metabolites were also examined by gas-liquid chromatography. Those specimens that reacted strongly to radioimmunoassay contained high concentrations of the drug or its metabolites. In the specimens examined by gas-liquid chromatography, the apparent concentrations of the metabolites were generally higher than those of the drug itself. Methaqualone in combination with its unconjugated metabolites reacted additively with the radioimmunoassay, resembling the same concentration of parent drug alone. Detection limits were between 10-200 mug/liter.