High-Performance Liquid Chromatography/Mass Spectrometry of Psychotropic Drugs

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We analyzed three representative psychotropic drugs, benzodiazepines, phenothiazines and butyrophenones, by our recently established system of capillary high-performance liquid chromatography (HPLC) /fast atom bombardment (FAB) -mass spectrometry (MS). The authentic compounds of 27 benzodiazepines, 17 phenothiazines and 6 butyrophenones were analyzed by the system. Quasi-molucular peaks along with adequate fragment peaks were detected in the positive mode for most compounds under investigation with the detection limit of less than 10ng on columun. Sensitivity in the nagative mode with respect to its mass spectral measurement was two order of magnitude lower than that in the positive mode.The extraction of the drugs from human blood or urine was studied using various solid-phase extraction cartridges. In general, C_<18> cartridges were effective for the isolation of benzodiazepines, C_2 cartridges for that of phenothiazines or butyrophenones. With this isolation procedure and the capillary HPLC/FAB-MS in the positive mode, some representative benzodiazepines or phenothiazines together with their metabolites could be identified in human sera after oral administration of them.We established a method for quantitative analysis of the concentration of midazolam, one of representative benzodiazepines, in serum by selected ion-monitoring (SIM) of FAB-MS, using deuterium-labeled midazolam as an internal standard. The calibration graph was linear for concentrations between 2ng/ml and 200ng/ml, and reproducibility was good. The capillary HPLC/FAB-MS was semi-quantitative for all compounds under investigation. However, we feel that accurate quantitation can be made by SIM of FAB-MS with a suitable isotopic internal standard. We also devised a simple method for quantitation of some benzodiazepines in human serum by UV monitoring of the capillary HPLC.These analytical methods devised in this study would seen to be useful in clinical pharmacology as well as in forensic toxicology.