ABSTRACT
Phenothiazines are widely used in the treatment of certain psychiatric disorders. Overdoses of these drugs are common and are potentially lives threatening of patients. This work aims to study the chromatographic and spectrophotometric behavior of some of commonly used phenothiazines [chlorpromazine hydrochloride and fluphenazine decanoate]. And estimation of the drugs to determine their distribution among different tissues, hair and body fluids of albino rats by using quick, sensitive and reliable method of analysis. The present study was conducted on ninety albino rats. The study divided into two parts [A and B] each involved 45 rats; A: The chemical and toxicological studies on chlorpromazine hydrochloride in toxic, lethal and chronic toxic doses. B: The chemical and toxicological studies on fluphenazine decanoate in toxic, lethal and chronic toxic doses. After extraction of chlorpromazine and fluphenazine from brain, liver, kidney, muscle, hair and plasma with ammonium sulphate, identification of the drugs was done using color tests and thin layer chromatography. UV spectrophotomeric and HPLC analysis of the samples was done. The results revealed that thin-layer chromatography gave positive results with tissue extracts of all organs and in all doses. It was obvious from the obtained results that the method used for spectrophotometric analysis offers the advantages of simplicity, specificity without the need of further extraction or heating, besides having higher sensitivity range than most of the existing spectrophotometric methods. The highest concentration of chlorpromazine was found in the kidney in all doses, followed by serum in toxic dose and liver in both lethal and chronic toxicity. Then the distribution varies in the other organs according to the different doses. The mean concentration of chlorpromazine was higher with HPLC than that with spectrophotometric method with significant difference in all organs. The order of distribution of fluphenazine in various organs of animals receiving the toxic dose by both HPLC and spectrophotometric methods was; [kidney, muscles, serum, liver, lung, hair, brain and heart] While the order of distributions of fluphenazine in various organs of animals received the lethal dose by the two methods was; [kidney, liver, serum, muscle, brain, hair, heart and lung] and that for animals receiving the chronic toxic dose was,[kidney, liver, serum, muscle, hair, brain, lung and heart]. It was clear that the order of distributions of chlorpromazine and fluphenazine in various organs in all doses was the same either by spectrophotometric or by HPLC methods, but the concentration of the drug was higher by HPLC than that by spectrophotometer and this difference was significant in all organs