Abstract
A rapid and simple method for determination of oxazolobenzodiazepines (oxazolam, haloxazolam, mexazolam, cloxazolam, and flutazolam) in sera was developed by gas chromatography (GC) using nitrogen-phosphorus detection (NPD) and a methyl silicone fused-silica wide-bore capillary (DB-1) column. Underivatized oxazolobenzodiazepine drugs gave relatively low sensitivity, because of decomposition during their passage through the column. On the other hand, on-column methylation of the oxazolobenzodiazepines with 0.4 mM trimethylanilium hydroxide in methanolic solution resulted in higher sensitivity; detection was possible at levels at least two to eight times lower than those without derivatization. The average recoveries of five oxazolobenzodiazepines from 0.5-ml volumes of sera containing 1.0 or 0.1 μg of each drug were 88–101% and 66–106%, respectively. The limits of detection of methylated oxazolobenzodiazepines by wide-bore capillary GC-NPD were 50–100pg on column. This method could be used for determination of the drugs in actual serum specimens with concentrations as low as 25–70ng/ml.
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