Determination of Diazepam and Nordiazepam in the Plasma of Psychiatric Patients in Long-Term Treatment Employing Liquid-Liquid and Solid Phase Extraction by Gas Chromatography with Electron Capture Detection

A sensitive, rapid, and reproducible gas chromatography-electron capture detection (GC-ECD) method was developed for the determination of diazepam (DZP) and N-desmethyldiazepam (nordiazepam, NDZP) in plasma of psychiatric patients in long-term treatment. Liquid-liquid (LLE) and solid phase (SPE) extractions were employed as techniques of sample preparation. For both techniques, the extraction solvent was hexane: methanol (9: 1) at pH 9.0. The recoveries ranged from 89 to 99% for DZP and from 53 to 69% for NDZ. Some validation parameters were found: linearity in spiked human plasma from 5 to 1200 ng mL−1 for DZP and 10 to 1200 ng mL−1 for NDZP using SPE and LLE techniques. The values for within- and between-day precision (% coefficient of variation) and accuracy (% relative error) were lower than 15%. The methods were applied to the analysis of samples from 54 patients under DZP treatment and proved to be suitable for routine therapeutic drug monitoring. Both studied techniques showed similar results with ...