Automated gas chromatography for studies of midazolam pharmacokinetics

Plasma midazolam concentrations following single therapeutic doses can be quantitated using electron-capture gas-liquid chromatography. After addition of a benzodiazepine analogue as an internal standard, samples are extracted with benzeneisoamyl 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 of midazolam per ml of plasma, and the variation of identical samples is 7 per cent or less. The method was used in a study of six females who received single intravenous 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, 7.2 (+/- 1.6) min; elimination half-life, 2.5 (+/- 0.2) h; total clearance, 8.1 (+/- 0.52) ml.min-1.kg-1.