[The development of the methods for the extraction, identification, and quantitative determination of alimemazine in the biological fluids from the laboratory animals under the acute poisoning conditions]. / Razrabotka metodik izolirovaniia, obnaruzheniia i kolichestvennogo opredeleniia alimemazina v biologicheskikh zhidkostiakh laboratornykh zhivotnykh pri ostrykh otravleniiakh.

There is the present-day tendency toward prescribing atypical neuroleptics for the management of neurologic and psychic disorders. Alimemazine appears to be very frequently used for this purpose due to the broad spectrum of its actions. At the same time, cases of alimemazine poisoning with the fatal outcome have been described. The objective of the present study was determine alimemazine in the biological fluids from the laboratory animals under the acute poisoning conditions. The experiments were carried with the use of the Wistar rats having 200 g body weight. Alimemazine was isolated from their biological fluids (blood plasma and urine) using the liquid-liquid extraction techniques developed specially for the purpose of this study. Alimemazine was extracted and quantitatively determined by HPLC and HPLC/MS. The method for the isolation of alimemazine from the urine and blood plasma is described. The results of the study give evidence that the maximum amount of the substance of interest can be extracted from the blood plasma within 1 hour after the administration of the toxic dose of alimemazine and within 2 hours after the administration of its therapeutic dose. The maximum amount of alimemazine in the urine is found within 3 hours after the administration of its therapeutic dose to the laboratory animals. It is concluded that the proposed methods for the extraction of alimemazine from the biological fluids can be included in the scheme of the chemical toxicological analysis of this substance.

[The chemical toxicological analysis of sertindole].

Sertindole is an "non-typical" neuroleptic extensively used for the treatment of schizophrenic patients. The detection of intoxication with this medication implies the necessity of development of the optimal methods for its isolation from the biological materials and further identification. The objective of the present work was to study the influence of various factors on the efficiency of sertindole extraction from solutions, the elaboration of the methods for its isolation from biological objects, detection, and quantitative determination in the extracts from these objects. Investigations into the influence of various factors on the isolation of sertindole from solutions included characteristic of the chemical nature of the organic solvent and the electrolyte, measurements of pH, time and frequency of extraction with the use of UV spectrophotometry. Isolation of sertindole from the liver, kidneys, brain, heart, gastric and intestinal contents was carried out by the method of A.A. Vasil'ev. Moreover, we have developed an original method for the detection of sertindole in the extracts using TLC, UV spectrophotometry, and HPLC. The qualitative determination of sertindole in the extracts from the internal organs, blood plasma, and urine was performed by HPLC. The optimal conditions for sertindole liberation from the extracts have been found and TLC-screening conditions proposed. The TLC, UV spectrophotometric, and HPLC techniques specially modified for the determination of sertindole in the extracts were used. It was shown that the maximum amounts of sertindole were present in the liver and brain within 24 hours after acute poisoning. In the kidneys, stomach, and intestines, it accumulated in smaller quantities Extracts from the heart did not contain sertindole. Maximum efficiency of the sertindole extraction during 24 hours was achived from blood plasma.

[Investigations of the distribution of aripiprazole in the internal organs and biological fluids of the laboratory animals in case of acute intoxication].

Despite the present-day extensive application of aripiprazole, there are many cases of its overdose and of poisoning with this compound. The objective of the present study was to detect and quantify aripiprazole in the internal organs and biological fluids of the laboratory animals in case of acute intoxication. The experiments were carried out on white mice of both sexes weighing 20.5 and 25.7 g. Aripiprazole was isolated from the liver, kidneys, brain, and heart as described by A.A. Vasil'eva and from the plasma and urine by the newly developed original methods. Aripiprazole was identified and quantitatively determined in the extracts from the aforementioned organs and tissues with the use of HPLC. The data obtained on the completeness of extraction from the liver, kidneys , and brain of the laboratory animals indicate that aripiprazole accumulated in the highest concentrations in the brain and kidneys within 24 hours after acute poisoning. Ist content was significantly lower in the liver while no traces of aripiprazole were found in the heart of the mice. The methods for aripiprazole isolation from the urine and blood plasma are described. The maximum amounts of aripiprazole were detected in blood plasma within 24 hours after acute intoxication. It is concluded that the proposed methods for aripiprazole isolation from the biological fluids (blood plasma and urine) can be included in the scheme of the chemical toxicological analysis of this compound.