High-performance liquid chromatographic assay with diode-array detection for toxicological screening of zopiclone, zolpidem, suriclone and alpidem in human plasma.

A high-performance liquid chromatographic assay with diode-array detection has been developed for the toxicological screening of the newly developed non-benzodiazepine hypnotics and anxiolytics zopiclone, zolpidem, suriclone and alpidem. After single-step liquid-liquid extraction of plasma at pH 9.5 using chloroform-2-propanol-n-heptane (60:14:26, v/v), the substances are separated on a Nova-Pak C18 4-microns column (300 mm x 3.9 mm, I.D.), with methanol-tetrahydrofuran-pH 2.6 phosphate buffer (65:5:30, v/v) as the mobile phase (flow-rate 0.8 ml/min). Full ultraviolet spectra from 200 to 400 nm are recorded on-line during the entire analysis and may be automatically compared to spectra stored in a library. The retention times of the four drugs are 4.05 min (zopiclone), 4.66 min (zolpidem), 6.74 min (suriclone) and 10.97 min (alpidem). The analysis is performed in 15 min. The method is simple, rapid and highly specific. It is the first assay to be described for convenient screening of cyclopyrrolones and imidazopyridines.