Absorption of triazolam from pelleted drug-diet mixtures by the mouse: quantitation of alpha-hydroxytriazolam in urine.

The absorption of triazolam from pelleted drug-diet mixtures by mice under steady-state conditions was determined for doses up to 150 mg/kg/day by measuring alpha-hydroxytriazolam, the principal urinary metabolite of triazolam in the mouse, in urine samples collected over a 24-hour period. Following beta-glucuronide glucuronosohydrolase hydrolysis of the urine, quantitation of alpha-hydroxytriazolam was accomplished using a specific reverse-phase liquid chromatographic method which utilized UV detection at 214 nm. Assay precision was greater than 2.7% (CV) over the concentration range of interest. Statistical analysis of the excretion data indicated that the mathematical relationship between the triazolam dose and the quantity of alpha-hydroxytriazolam excreted was linear for female mice and nonlinear for male mice. Triazolam absorption, as reflected by alpha-hydroxytriazolam urinary excretion data, increased with triazolam dose.