Gas Chromatographic— Mass Spectrometric Analysis of Antidepressants, Neuroleptics, and Benzodiazepines

Gas chromatography-mass spectrometry (GC-MS) has been used for the identification of drugs since 1968 when Hammar and coworkers (1968) employed this technique for the analysis of chlorpromazine and some of its metabolites isolated from human blood. Since that time this analytical procedure has been succeβfully adapted for the analysis of many psychotropic drugs. Clinical applications of GC-MS have been reviewed (Hill and Whelan, 1984; Harvey, 1984). This review will be concerned with the application of MS to the identification and quantitation of anti-depreβants, neuroleptics, benzodiazepines, and their metabolites isolated from a complex biological matrix. When used in combination with the excellent separating power of GC, the combmed GC-MS provides an analytical technique that is highly selective and sensitive and has the versatility to quantitatively determine levels of psychotropic drugs and their relevant metabolites. These properties make MS the method of choice for the analysis of these compounds. Disadvantages of this technique, however, include the initial high cost of equipment, the sophisticated level of skill required for the operation and maintenance of the instrumentation, and the difficulty in interpretation of the data. For these reasons MS is not used for the routine analysis of these drugs and metabolites, but is used in those cases in which low levels are expected and high sensrtrvrty is required, positive identrfication of drugs is mandatory, such as in drug screens or overdoses, and studies elucidating the structure of the metabolites of these compounds. In addition, MS is used as a reference method for vahdating other analytical procedures, in bioavailability studies, in testing the purity of various preparations, and in verifying the structure of various chemical derivatives. The GC-MS technique has been used in both research and clinical investigations to determine levels of these drugs and metabolites from the low picogram to the microgram range.