[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.

[Chemical toxicological analysis of haloperidol metabolite 4-(4-chlorophenyl)-4-hydroxypipiridine in urine by high-performance liquid chromatography].

Haloperidol is extensively used in current psychiatric practice for the treatment of various psychotic disorders. However, this substance is known to be toxic and sometimes cause poisoning despite its generally positive therapeutic effect. Moreover, some of its metabolites also possess high toxic activity. It has been shown in the literature that haloperidol is metabolized to 4-(4-chlorophenyl)-4-hydroxypiperidine (CPHP) and 3-(4-fluorobenzoyl)-propionic acid (FBPA). We have developed the most efficacious method for isolation of both CPHP and FBPA from aqueous solutions ensuring the output of 99.6% and 99.8% of the respective product. Also, their spectral characteristics were studied by the UV spectrophotometric technique. Animal experiments demonstrated that only CPHP was excreted in the urea whereas the second metabolite was not detected in any sample, probably because it is further metabolized to 3-(4-fluorophenyl)-acetic acid. Methods for the isolation of CPHP from urine, its identification, and quantitative determination were developed based on the use of high-performance liquid chromatography (HPLC).

[Chemico-toxicological analysis of haloperidol in blood with high-performance liquid chromatography in combined poisoning].

Haloperidol is widely used in psychiatric practice both in monotherapy and in combination with neuroleptics, phenothiazine derivatives (chlorpromasin, levomepromasin) and antidepressants (amitriptilin, imipramin). We have developed techniques of haloperidol isolation from blood in combined poisonings with phenothiazine derivatives (chlorpromazine, levomepromasine) and antidepressants (amitriptilin, imipramin), their identification and quantitation with high-performance liquid chromatography. The highest output of the substances studied was achieved in alkaline hydrolysis. The techniques are expressive, sensitive and well reproducible. This makes them convenient for practice of forensic-chemical and chemico-toxicological laboratories.

[The analysis of tiapride in cadaveric material].

To optimize conditions of tiapride isolation from cadaveric organs, we compared the results of conventional methods by Stas-Otto, A.A. Vasilyeva and V.F. Kramarenko which provide tiapride isolation up to 50% and a new precise and reproducible method providing 60 +/- 2% tiapride isolation. Identification of tiapride isolated from cadaveric material was made with thin-layer chromatography and high performance liquid chromatography. The latter assay employed the method of external standard. The original techniques proposed identify and measure tiapride in hepatic samples in the presence of unidentified endogenic compounds. The techniques are rapid, selective, sensitive and reproducible.

[Identification of haloperidol and tiapride in the urine with thin layer chromatography].

How to identify haloperidol and tiapride in the urine by thin layer chromatography was proposed. Optimal systems of solvents were selected by chromatographic mobility of the substances studied in 14 solvents with different polarity. The findings allowed making an optimal choice of the composition and proportion of the solvents. Diethylamine, as a basic modifier, was introduced in the system of solvents. This improved chromatographic mobility of haloperidol and tiapride. Optimal mobile phases, developers were found, the threshold of detectability of the substances in the given conditions was established. The techniques were used for identification of haloperidol and tiapride in the samples from model urine mixture in the presence of non-identified endogenic compounds. They are characterized by rapid performance, selectivity, sensitivity and good reproducibility and can be introduced into practice of chemicotoxicological laboratories.