Thirty Years of Antipsychotic Drug Analysis
Interest in measurement of psychotropic drugs in biological fluids dates back to -1955, soon after the introduction of chlorpromazine into psychiatry . 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 . Early attempts involved UV spectrophotometry and colorimetry, with or without prior derivatization . 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.
KeywordsParent Drug Psychotropic Drug Tertiary Amine Amine Oxide Prior Derivatization
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- 1.Salzman, N.P. & Brodie, B.B.(1956) J. Pharmacol. Exp. Ther. 118, 46–54.Google Scholar
- 2.Forrest, F.M., Forrest, I.S. & Mason, A.S. (1961) Ain. J. Psychiat. 118, 300–307.Google Scholar
- 6.Curry, S.H. & Evans, S. (1975) Psychpharm. Comm. 1, 481–490.Google Scholar
- 10.Whelpton, R., Curry, S.H. & Watkins, G.M. (1982) J. Chromatog. 228, 321–326.Google Scholar
- 11.Curry, S.H., Brown, E.A., Hu, O. Y-P. & Perrin, J.H. (1982) J. Chromatog. 231, 361–376.Google Scholar
- 12.Midha, K.K., Loo, J.C.K., Hubbard, J.W., Rowe, M.L. & McGilveray, I.J. (1979) Clin. Chem. 25, 166–168.Google Scholar
- 21.Garratini, S., Mussini, E. & Randall, L.O., eds. (1973) The Benzodiazepines, Raven Press, New York, 685 pp.Google Scholar
- 23.Hammer, W. & Brodie, B.B. (1967) J. Pharmacol. Exp. Ther. 157, 503–508.Google Scholar
- 24.Smith, R.C., Dekirmenjian, H., Davis, J.M., Crayton, J. & Evans, J. (1977) Comm. Psychopharmacol. 1, 319–324.Google Scholar
- 25.Rieder, J. (1965) Arzneim.-Forsch./Drug Res. 15, 1134–1148.Google Scholar