Measurement of thioridazine in blood and urine.

Abstract

1 Thioridazine can be specifically, simply, and reliably measured in plasma and urine by gas chromatography using hexane extraction and prochlorperazine as internal standard; fluorimetry is non‐specific. 2 The method can also measure thioridazine ring sulphoxide, and mesoridazine‐plus‐sulphoridazine (M/S). 3 After single doses plasma sometimes shows M/S in addition to thioridazine itself; it always does so on continued treatment. There is great individual variation in both components, and evidence of changes in metabolism during the early weeks. 4 Urinary excretion may be influenced by pH, but between pH 6.0‐ 7.0 about 1% of the daily dose appears in 24 h urine as the following: free thioridazine in microng quantities, M/S and ring sulphoxide each in mg amounts. 5 Patients attain steady state conditions, although plasma levels rise considerably after each dose and settle again in about 10 h. After chronic treatment is stopped to half‐life is at about 30 h. 6 Plasma levels cannot be related to therapeutic response when this is slow, as in schizophrenia, but interpretations are complicated by the production of clinically active metabolites, and by plasma protein binding.

Plasma Level Monitoring of Antipsychotic Drugs

“…However, investigators using GLC procedures (Buyze et aI., 1973;Martensson and Roos, 1973;and Ng and Crammer, 1977) have been unable to show any significant relationship between plasma levels of thioridazine and/or metabolites and clinical improvement. Vanderheeren and Muusze (( 977) however suggest, without statistical analysis, that in a group of young acute schizophrenics 'mostly within one year of onset of symptoms', that the rate of improvement was related more to the active mesoridazine metabolite level than to thioridazine itself.…”

“…Utilising this technique a major unknown metabolite of thioridazine and mesoridazine found in the plasma of schizophrenic patients and normal volunteers was subsequently identified as sulphoridazine (Gruenke and Craig, 1975). Ng and Crammer (1977) have published another modification of the Curry and. Mould (1969) technique which involves changes in column dimensions, solvent used in extraction and internal standard.…”

A Randomized Evaluation of the Effects of Six Antipsychotic Agents on QTc, In the Absence and Presence of Metabolic Inhibition

“…[19][20][21][22][23][24] Investigators were permitted to vary the titration schedule, or to hold the dose at a submaximal level, depending on tolerability.…”

Prolactin and psychophysiologic measures after single doses of thioridazine

“…Thioridazine and metabolites. A gaschromatographic technique developed by Curry and Mould 1 and modified by us 9 was used for the determination of thioridazine and its metabolites in both plasma and urine specimens. The method is highly specific for thioridazine and has aresolution of I ng/ ml.…”

“…They did not measure prolactin. We have taken advantage of a specific method for quantifying thioridazine in blood and urine 9 to study the effects of a single dose of this phenothiazine in normal men on both prolactin and psychophysiologic test responses in further clarification of the nature of individual responses to psychotropics.…”