Thirty Years of Antipsychotic Drug Analysis

Abstract

Interest in measurement of psychotropic drugs in biological fluids dates back to -1955, soon after the introduction of chlorpromazine into psychiatry [1]. It was quickly realized that studies of chlorpromazine in regard to its disposition and metabolism, and detection in urine as a means of assessing compliance, would be useful [2]. Early attempts involved UV spectrophotometry and colorimetry, with or without prior derivatization [3]. However, it was not till GC-ECD was applied that sufficient sensitivity for plasma was achieved [4, 5]. Over the years, nitrogen detectors, mass spectrometry (MS) and liquid chromatography have been used [6–12]. Basically* the strategy has had to continuously evolve to keep up with knowledge about metabolites of the drugs concerned [13–20].

Benzodiazepine analysis has been relatively straightforward [21, 22]. Most benzodiazepines are amenable to GC-ECD, offsetting the reZativeZy limited applicability of HPLC. Generally benzodiazepines are not so beset with the problems of non-separability of drugs from one another, and drugs from metabolites, as are phenothiazines and tricyclic antidepressants. TricycZics were initially measured by isotope derivatization techniques [ 23], needing prior specific extraction of the drug. GC-NPD was later applied; but again, HPLC with UV-absorption or fluorescence detection has provided a solution to most problems.