Automated Gas Chromatography for Studies of Midazolam Pharmacokinetics

Abstract

Plasma midazolam concentrations following simple therapeutic doses can be quantitated using electron-capture GLC. After addition of a benzodiazepine analog as an internal standard, samples are extracted with benzene-isoamyl alcohol (98.5:1.5). The organic extract is evaporated to dryness, reconstituted and chromatographed on an SP-2250 liquid phase. The automatic sampler allows up to 100 chromatographic analyses per 24 h period. The sensitivity limits are 2-3 ng midazolam per ml of plasma, and the variation of identical samples is .ltoreq. 7%. The method was used in a study of 6 females who received single i.v. doses of midazolam for purposes of anesthetic induction prior to minor gynecologic procedures. Mean (.+-. SE) kinetic variables for midazolam were: volume of central compartment, 0.37 (.+-. 0.06) l/kg; total volume of distribution, 1.72 (.+-. 0.05) l/kg; initial distribution half-life [t1/2], 7.2 (.+-. 1.6) min; elimination t1/2, 2.5 (.+-. 0.2) h; total clearance, 8.1 (.+-. 0.52) ml/min per kg.