Determination of chlordiazepoxide in mouse plasma by gas chromatography-negative-ion chemical ionization mass spectrometry.

A gas chromatographic-negative-ion chemical ionization mass spectrometric (GC-NCIMS) method for the determination of chlordiazepoxide (Librium) in mouse plasma is described. Chlordiazepoxide was not suitable for GC analysis because of its thermal instability. The specific derivatization technique described permits the analysis using GC-MS with high sensitivity and selectivity. The use of halazepam as an internal standard instead of an isotopic internal standard decreases the cost and time of the analysis. The detection limit for chlordiazepoxide was 0.1 ng/ml with an injection volume of 1 microliter at a signal-to-noise ratio > 5. The limit of quantification was 5 ng/ml.