Pilot pharmacokinetic study of brotizolam, a thienodiazepine hypnotic, using electron-capture gas-liquid...

Brotizolam, a thienodiazepine hypnotic, can be reliably and sensitively quantitated in human plasma using gas chromatography with electron-capture detection. After addition of an internal standard, samples are directly extracted into an organic solvent, evaporated, reconstituted, and chromatographed at 290 degrees C on a 1% OV-17 column. Sensitivity limits are 0.25 ng of brotizolam/ml of plasma. Six volunteers ingested single 0.25- and 0.5-mg doses of brotizolam on two occasions, and brotizolam concentrations were measured in plasma samples drawn during 24 h after each dose. Peak concentrations averaged 5.5 and 9.2 ng/ml at the two dose levels, and were always attained within 1.5 h after dosage. Elimination half-life averaged 4.4 h (range 2.6-6.9 h) and was independent of dose. Thus brotizolam is a rapidly absorbed hypnotic drug with a short elimination half-life.