Skip to main content
Log in

A mass fragmentographic method for the determination of chlorpromazine and two of its active metabolites in human plasma and CSF

Psychopharmacology Aims and scope Submit manuscript

Abstract

A mass fragmentographic method for the quantitation of chlorpromazine (CPZ), monodemethyl-chlorpromazine (nor1-CPZ), and 7-hydroxychlorpromazine (7-OH-CPZ) in plasma, cerebrospinal fluid, and tissues has been developed. The deuterated analogues of the compounds are used as internal standards. The high specificity was ascertained by multiple ion determination. The experimental error is below 10%. The sensitivity allows determination of sub ng quantities of CPZ per ml cerebrospinal fluid. The method has been applied to the analysis of drug concentrations in plasma and cerebrospinal fluid (CSF) of chlorpromazine-treated patients. The amount of CPZ in CSF was about 3% of the plasma level. The CPZ levels in plasma and CSF were significantly correlated.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Alfredsson, G., Sedvall, G.: Mass fragmentographic analysis of chlorpromazine in human plasma. In: Antipsychotic drugs: pharmacodynamics and pharmacokinetics, G. Sedvall, B. Uvnäs, and Y. Zotterman, eds. Oxford: Pergamon Press (in press, 1976)

    Google Scholar 

  • Brookes, L.-G., Holmes, M.-A., Forrest, I.-S., Bacon, V.-A., Duffield, A.-M., Solomon, M.-D.: Chlorpromazine metabolism in sheep. II. In vitro metabolism and preparation of 3H-7-hydroxychlorpromazine. Agressologie 12, 333–342 (1971)

    Google Scholar 

  • Chan, T. L., Sakalis, G., Gershon, S.: Quantitation of chlorpromazine and its metabolites in human plasma and urine by direct spectrodensitometry of thin-layer chromatograms. In: Advances in biochemical psychopharmacology, Vol. 9, I. S. Forrest, C. J. Carr, and E. Usdin, eds., pp. 323–333. New York: Raven Press 1974

    Google Scholar 

  • Craig, J. C., Mary, N. Y., Roy, S. K.: Application of gas chromatography to the detection of tert-amine oxides. Analyt. Chem. 36, 1142–1143 (1964)

    Google Scholar 

  • Crane, G. E.: Risks of long-term therapy with neuroleptic drugs. In: Antipsychotic drugs: pharmacodynamics and pharmacokinetics, G. Sedvall, B. Uvnäs, and Y. Zotterman, eds. Oxford: Pergamon Press (in press, 1976)

    Google Scholar 

  • Curry, S. H.: Determination of nanogram quantities of chlorpromazine and some of its metabolites in plasma using gas-liquid chromatography with an electron capture detector. Analyt. Chem. 40, 1251–1255 (1968)

    Google Scholar 

  • Curry, S. H.: Relation between binding to plasma protein, apparent volume of distribution, and rate constants of disposition and elimination for chlorpromazine in three species. J. Pharm. Pharmacol. 24, 818–819 (1972)

    Google Scholar 

  • Curry, S. H.: Metabolism and kinetics of chlorpromazine in relation to effect. In: Antipsychotic drugs: pharmacodynamics and pharmacokinetics, G. Sedval, B. Uvnäs, and Y. Zotterman, eds., Oxford: Pergamon Press (in press, 1976)

    Google Scholar 

  • Forrest, I. S., Carr, C. J., Usdin, E.: Phenothiazines and structurally related drugs. In: Advances in biochemical psychopharmacology, Vol. 9. New York: Raven Press 1974

    Google Scholar 

  • Kaul, P. N., Ticku, M. K., Clark, M. L.: Chlorpromazine metabolism. V. Disposition of free and conjugated metabolism in blood fractions of schizophrenic patients. J. pharm. Sci. 61, 1753–1757 (1972)

    Google Scholar 

  • Kawashima, K., Dixon, R., Spector, S.: Development of radioimmunoassay for chlorpromazine. Europ. J. Pharmacol. 32, 195–202 (1975)

    Google Scholar 

  • Loga, S., Curry, S., Lader, M.: Interactions of orphenadrine and phenobarbitone with chlorpromazine: Plasma concentrations and effects in man. Brit. J. clin. Pharmacol. 2, 197–208 (1975)

    Google Scholar 

  • Mackay, A. V. P., Healey, A. F., Baker, J.: The relationship of plasma chlorpromazine to its 7-hydroxy and sulphoxide metabolites in a large population of chronic schizophrenics. Brit. J. clin. Pharmacol. 1, 425–430 (1974)

    Google Scholar 

  • Manian, A. A., Piette, L. H., Holland, D., Grover, T., Leterrier, F.: Red blood cell drug binding as a possible mechanism for tranquilization. In: Advances in biochemical psychopharmacology, Vol. 9, I. S. Forrest, C. J. Carr, and E. Usdin, eds., pp. 149–161. New York: Raven Press 1974

    Google Scholar 

  • Miller, R. J., Iversen, L. L.: Effect of chlorpromazine and same of its metabolites in the dopamine-sensitive adenylate cyclase of rat brain striatum. J. Pharm. Pharmacol. 26, 142–144 (1974)

    Google Scholar 

  • Nybäck, H., Sedvall, G.: Effect of chlorpromazine and some of its metabolites on synthesis and turnover of catecholamines formed from 14C-tyrosine in mouse brain. Psychopharmacologia (Berl.) 26, 155–160 (1972)

    Google Scholar 

  • Rivera-Calimlim, L., Castaneda, L., Lasagna, L.: Effects of mode of management on plasma chlorpromazine in psychiatric patients. Clin. Pharmacol. Ther. 14, 978–986 (1973)

    Google Scholar 

  • Sedvall, G.: Receptor feedback and dopamine turnover in CNS. In: Handbook of psychopharmacology, Vol. 6, L. L. Iversen, S. D. Iversen, and S. H. Snyder, eds., pp. 127–177. New York: Plenum 1975

    Google Scholar 

  • Wiesel, F.-A., Alfredsson, G.: A mass fragmentographic study on the pharmacokinetics of chlorpromazine and the relation to effects on monoamine metabolism in the rat brain (to be published)

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Alfredsson, G., Wode-Helgodt, B. & Sedvall, G. A mass fragmentographic method for the determination of chlorpromazine and two of its active metabolites in human plasma and CSF. Psychopharmacology 48, 123–131 (1976). https://doi.org/10.1007/BF00423250

Download citation

  • Received:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00423250

Key words

Navigation