ABSTRACT
A selective oxidation of thioridazine to give exclusively its ring sulfoxides and a separation of the resulting products as diastereoisomeric pairs of enantiomers (DL, LD and DD, LL) are reported. These pairs were characterized by TLC, high-performance liquid chromatographic, IR, UV, 1H-NMR, 13C-NMR, GC-MS, and elemental analyses, and by reduction to thioridazine by lithium aluminum hydride. Structural data for the separated diastereoisomeric pairs or their nitric acid salts were obtained from NMR and IR studies. Gram quantities of each of the two diastereoisomeric pairs of enantiomers were isolated in better than 99% purity.
Subject(s)
Cyclic S-Oxides/chemical synthesis , Thioridazine/chemical synthesis , Chemical Phenomena , Chemistry , Chromatography, High Pressure Liquid , Chromatography, Thin Layer , Cyclic S-Oxides/isolation & purification , Hydrogen Peroxide , Hydrogen-Ion Concentration , Nitrous Oxide , Oxidation-Reduction , Stereoisomerism , Thioridazine/analogs & derivatives , Thioridazine/isolation & purificationSubject(s)
Chlorpromazine/urine , Animals , Biotransformation , Chromatography, Thin Layer , Female , Haplorhini , Humans , Macaca mulatta , Male , Methods , Phenols/urine , Sulfoxides/urineABSTRACT
Lactating squirrel monkeys chronically receiving 2 mg/kg delta-9-tetrahydrocannabinol (THC) orally either two or five times weekly were given a tracer dose of 14C-delta-9-THC mixed with the delta-9-THC. This permitted radioquantitation of the THC in milk specimens collected 1 to 24 hr after administration of the labeled dose. Correlated specimens of urine and feces were also collected individually from mothers and infants and were subjected to radioquantitation and exploratory TLC. During the 24-hr observation period, approximately 0.2% of the labeled delta-9-THC appeared in the milk, whereas 42% and 1% were excreted in the feces and urine, respectively. Infants that suckled during the 6 hr immediately after their mothers were administered the labeled compound excreted an average of 0.01% and 0.12% of the mother's dose in the urine and feces, respectively, during the 18 hr after suckling.
Subject(s)
Dronabinol/metabolism , Milk/metabolism , Animals , Cannabinoids/metabolism , Female , Haplorhini , Lactation , Pregnancy , Saimiri , Time FactorsSubject(s)
Chlorpromazine/urine , Adsorption , Animals , Haplorhini , Hydrogen-Ion Concentration , Macaca mulatta , Research Design , Temperature , Time FactorsABSTRACT
The use of tritiated chlorpromazine to correlate total excretion of radioactivity with characterization of the radioactive metabolites had shown a substantial discrepancy. While radioactivity was totally excreted and accounted for within three weeks, recognizable chlorpromazine metabolites represented only about two thirds of the radioactivity in any given sample. To rule out tritium exchange, 14C-labeled chlorpromazine was administered to Rhesus monkeys. The same discrepancy was observed, primarily in the conjugated drug fraction. Therefore, all unconjugated chlorpromazine metabolites were exhaustively extracted, and an alkaline hydrolysis performed. The aglycones liberated thereby were again carefully removed, and the residual aqueous fraction was subjected to an acid hydrolysis. This procedure yielded an additional group of known and unknown phenolic chlorpromazine aglycones, representing approximately one third of the radioactivity in the whole urine. Preliminary trials on urine pools of patients chronically dosed with chlorpromazine yielded essentially the same results. The structure of this new class of chlorpromazine conjugates has not yet been elucidated, nor is the ligand known at this time. A glucoside-type bond may characterize this significant class of chlorpromazine.