Abstract
Thirteen phenothiazine compounds were separated chromatographically using high performance liquid chromatography with coulometric electrochemical detection. These could be extracted from brain tissue using direct homogenization in tetrahydrofuran followed by one centrifugation, evaporation of supernatant and reconstitution in water. Fluphenazine was used as the internal standard. The absolute lower limit of detection was approximately 50 pg/mg wet tissue, and recovery rates for most standards added to brain homogenates were greater than 85%. Chromatograms from patients receiving chlorpromazine (600 mg) and thioridazine (600 mg) are shown and endogenous brain levels quantified. The results are discussed with respect to their relevance in schizophrenic research.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Akpofure C, Riley CA, Sinkule JA, Evans WE (1982) Quantitation of daunorubicin and its metabolites by high-performance liquid chromatography with electrochemical detection. J Chromatogr 232:377–383
Alfredsson G, Wode-Helgodt B, Sedvall G (1976) A mass fragmentographic method for the determination of chlorpromazine and two of its active metabolites in human plasma and CSF. Psychopharmacology 48:123–131
Cooper JK, McKay G, Midha KK (1983) Subnanogram quantitation of chlorpromazine in plasma by high-performance liquid chromatography with electrochemical detection. J Pharm Sci 72:1259–1262
Creese I, Snyder SH (1977) A simple and sensitive radioreceptor assay for antischizophrenic drugs in blood. Nature 270:180–182
Curry SH, Brown EA, Hu OY-P, Perrin JH (1982) Liquid chromatographic assay of phenothiazine, thioxanthene and butyrophenone neuroleptics and antihistamines in blood and plasma with conventional and radial compression columns and UV and electrochemical detection. J Chromatogr 231:361–376
Davis CM, Harrington CA (1984) Quantitative determination of chlorpromazine and thioridazine by high-performance thin layer chromatography. J Chromatogr Sci 22:71–74
Dinovo EC, Bost RO, Sunshine I, Gottschalk LA (1978) Distribution of thioridazine and its metabolites in human tissues and fluids obtained postmortem. Clin Chem 24:1828–1830
Green DE, Forrest IS, Forrest FM, Serra MT (1965) Inter-patient variation in chlorpromazine metabolism. Exp Med Surg 23:278–287
Kaul PN, Whitfield LR, Clark ML (1976) Chlorpromazine metabolism VII: new quantitative fluorometric determination of chlorpromazine and its sulfoxide. J Pharm Sci 65:689–694
Kilts CD, Knight DL, Mailman RB, Widerlov E, Breese GR (1984) Effects of thioridazine and its metabolites on dopaminergic function: Drug metabolism as a determinant of the antidopaminergic actions of thioridazine. J Pharmacol Exp Ther 231:334–342
Kilts CD, Patrick KS, Breese GR, Mailman RB (1982) Simultaneous determination of thioridazine and its S-oxidized and N-demethylated metabolites using high-performance liquid chromatography on radially compressed silica. J Chromatogr 231:377–391
Linnoila M, Rosenblatt JE, Jeste D, Skinner T, Potter WZ, Wyatt RJ (1982) Disparate serum thioridazine concentrations: liquid chromatography versus radioreceptor assay. Acta Pharmacol Toxicol 50:25–29
Mailman RB, DeHaven DL, Halpern EA, Lewis MH (1984) Serum effects confound the neuroleptic radioreceptor assay. Life Sci 34:1057–1064
McKay G, Geddes J, Cowper MJ, Gurnsey TS (1983) Recent advances in the analysis of phenothiazine drugs and their metabolites using high performance liquid chromatography. Prog Neuropsychopharmacol Biol Psychiatry 7:703–707
Murakami K, Murakami K, Ueno T, Hijikata J, Shirasawa K, Muto T (1982) Simultaneous determination of chlorpromazine and levomepromazine in human plasma and urine by high-performance liquid chromatography using electrochemical detection. J Chromatogr 227:103–112
Shibanoki S, Gotoh Y, Ishikawa K (1984) Determination of chlorpromazine in the blood and brain of mice by high performance liquid chromatography combined with electrochemical detection. Jpn J Pharmacol 35:169–174
Skinner T, Gochnauer R, Linnoila M (1981) Liquid chromatographic method to measure thioridazine and its active metabolites in plasma. Acta Pharmacol Toxicol 48:223–226
Smith DJ (1981) The separation and determination of chlorpromazine and some of its related compounds by reversed-phase high performance liquid chromatography. J Chromatogr Sci 19:65–71
Stoll AL, Baldessarini RJ, Cohen BM, Finklestein SP (1984) Assay of plasma thioridazine and metabolites by high-performance liquid chromatography with amperometric detection. J Chromatogr 307:457–463
Tandler CJ, Fiszer de Plazas S (1975) The use of tetrahydrofuran for delipidation and water solubilization of brain proteolipid proteins. Life Sci 17:1407–1410
Vanderheeren FA, Theunis DJ (1976) Gas-liquid chromatographic determination of perazine, thioridazine and thioridazine metabolites in human plasma. J Chromatogr 120:123–128
Wallace JE, Shimek EL Jr, Stavchansky S, Harris SC (1981) Determination of promethazine and other phenothiazine compounds by liquid chromatography with electrochemical detection. Anal Chem 53:960–962
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Svendsen, C.N., Bird, E.D. HPLC with electrochemical detection to measure chlorpromazine, thioridazine and metabolites in human brain. Psychopharmacology 90, 316–321 (1986). https://doi.org/10.1007/BF00179183
Received:
Issue Date:
DOI: https://doi.org/10.1007/BF00179183