1: Ther Drug Monit 1997 Jun;19(3):352-7
A rapid high-performance liquid chromatographic method for the measurement
of midazolam plasma concentrations during long-term infusion in ICU patients.
Van Brandt N, Hantson P, Mahieu P, Verbeeck RK
School of Pharmacy, Faculty of Medicine, Catholic University of Louvain,
Brussels, Belgium.
A new high-performance liquid chromatographic method was developed for
quantification of midazolam in plasma samples from intensive care unit
patients on long-term intravenous infusion of this benzodiazepine. Plasma
samples (0.5 ml) were mixed with 1 microgram flurazepam (internal standard),
alkalinized with 2.5 N NaOH, and extracted with toluene. The organic phase
was evaporated to dryness, and the residue was dissolved in the mobile
phase (acetonitrile/0.05 M phosphate buffer pH 4.5) and injected into the
analytical column (C18 Nova-Pak 3.9 x 150 mm, 4 microns, maintained at
room temperature; mobile phase flow rate: 1.2 ml/minute). The eluate was
monitored at 207 nm, which reduced the risk of interferences from concurrent
medications. Retention times of flurazepam, 1'-hydroxymidazolam (an active
metabolite) and midazolam were approximately 4.5, 6.1 and 13.5 minutes,
respectively. The assay was linear over the range 100 to 3000 ng/ml. The
coefficients of variation of the within-day and between-day assay for the
100 to 3000 ng/ml range were < 5% and < 7%, respectively. The developed
method is fast, reproducible, and well suited to monitor steady state midazolam
plasma concentrations in clinical samples.
PMID: 9200778, UI: 97344302