[The determination of amitriptyline and its metabolite, nortriptyline, in the biological objects of the corpse by the high-performance liquid chromatography technique].

Tricyclic antidepressants are among the preparations that most frequently cause intoxication in adults and children; moreover, poisoning with these substances not infrequently has a fatal outcome. Medications belonging to this group, such as amitriptyline, are extensively used to manage manifestations of depression, anxiety, migraine, neuropathic pain, and hyperactivity syndrome. Amitriptyline overdosage causes non-specific symptoms of intoxication, and its clinical picture does not allow to identify the nature of a psychotropic xenobiotic. Of primary importance in connection with this is to establish the cause of intoxication or death by the clinical toxicological and forensic medical methods based on the results of the fast identification and quantitation of amitriptyline in biological materials including blood, urine, hepatic tissues, etc. The authors describe the method for the determination of amitriptyline and its principal physiological metabolite nortriptyline in biological objects with the help of high performance liquid chromatography (HPLC).

[The peculiarities and prospects of the investigations of ptomaines for the purpose of forensic medical analysis].

This review of the literature presents the results of analysis of the publications concerning the prospects of the investigations of ptomaines including their influence on the results of determination of toxic substances present in the putrescent cadaveric tissues and on the persistence of analytes in the biological materials. Special emphasis is laid on the peculiarities of investigation of ptomaines and the necessity of the further development of the methods for the detection, isolation, and identification of toxicants in the putrescent and exhumed biological objects bearing in mind that such studies are not infrequently provide the sole opportunity to prove intoxication with certain substances.

[Forensic chemistry as a pharmaceutical discipline].

The principal objectives and problems facing forensic chemistry expertise are considered. In addition, its development as a pharmaceutical discipline, its goals and practical tasks are discussed.

[The problems of expert evaluation of the results of forensic chemical investigations of clozapine in the biological material].

The objective of the present review was to analyse the problems of expert evaluation of the results of forensic chemical investigations of clozapine in the biological material. Such an analysis is needed because many topical aspects of the quantitative evaluation of toxic clozapine concentrations remain unclear. The treatment with clozapine is associated with its accumulation in blood in concentrations up to 2 mg/l in the absence of any toxic effect allegedly due to the development of tolerability of this agent. In the tolerant patients the ratio of the main clozapine metabolite, norclozapine, to clozapine itself in the serum amounts to 0.6-0.9. This value falls down to 0.3-0.4 in case of acute intoxication. In the case of identification of other pharmaceutical products narcotic drugs together with clozapine their influence on the activity of enzymes responsible for clozapine biotransformation should be taken into consideration. The concomitant intake of clozapine and alcohol may be dangerous for the clozapine-intolerant subjects. It is concluded that the above observations must be borne in mind in the assessment of the results of forensic chemical analysis.

[The determination of clozapine for the forensic chemical study of the cadaveric blood, urine, and liver using high performance liquid chromatography].

The method for the determination of clozapine during chemical studies of cadaveric blood, urine, and liver (kidneys) has been developed based on the use of high performance liquid chromatography. Clozapine losses were estimated at 40-60% with the fractional uncertainty below 10-11% and the detection limit of 0.001 mg%. An algorithm for the estimation of the quality of clozapine isolation and the results of analysis of individual samples is proposed.

[The method for expert assessment as a tool for the improvement of the methodological basis of the activities of a bureau of forensic medical expertise].

An important aspect of the problem of iatrogenic poisoning is the lack of comprehensive relevant information. Many experts employed at the bureaus of forensic medical expertise believe that this problem can be resolved only based on a multifaceted approach. The results of questionnaire studies and cause-and-effect analysis allowed the following recommendations to be proposed for addressing the problem under consideration: making a minimal list of equipments necessary to maintain activities of forensic medical departments, updating the list of toxic substances to be studied in the laboratories of bureaus of forensic medical expertise, modification of the reporting form No 42 to be filled by such bureaus. The optimal approach is thought to be the equipment of all bureaus in compliance with the universal requirements, introduction of standard methods and technologies for the analysis of the materials included in the list of toxic substances to be determined.

[Determination of morphine and codeine in forensic chemical studies with the use of a single quadrupole mass-selective detector coupled to the HPLC system].

It was shown that a single quadrupole mass-selective detector coupled to the HPLC system can be used in forensic chemical practice for the detection and quantitative measurement of morphine and codeine in forensic in various biological objects. An algorithm for the reliable identification of opiates in a concentration range starting from 0.002 mg% with a relative error below 20% (mean ca 9.5%) is proposed.

[Drug intoxications as an indicator of social tensions and social ill-being].

Taken together statistical data illustrating the frequency of acute iatrogenic intoxication and parameters of economic development of the country testify to the importance of the problem of drug abuse confirmed by calculation of Piearson's correlation coefficients. The analysis of the rating list of pharmaceutical products known to most frequently cause intoxication indicates that a group of potentially dangerous' preparations include not only prescription drugs, such as neuroleptics, antidepressants, and soporifics, but also over-the-counter medicines. The results of the present study give evidence of the appearance of a separate nosological form in this country referred to as iatrogenic diseases. Moreover, they give reason to regard iatrogenic intoxication as a risk factor of social tensions and ill-being.

[Correction of the alkylnitrite method for the detection of ethanol in blood taking into account toxico-kinetic and anthropometric data].

The correction coefficient for the systemic inaccuracy arising during determination of blood ethanol by alkylnitrite gas chromatography and concomitant calibration of aqueous solutions was estimated to equal 0.82; this finding was confirmed by the results of the toxico-kinetic assay for the measurement of total body water (TBW) from the kinetic curve characterizing the time dependence of ethanol concentration in the exhaled air, saliva, capillary and venous blood in combination with 4 anthropometric methods and (in several cases) direct physical detection of TBW. When detecting the blood ethanol level with a correction coefficient of 0.82, the mutual position of the kinetic curves for ethanol concentrations in the blood and the exhaled air (recalculated for the blood level with a coefficient of 2100) as well as in the blood and saliva agreed with that reported in the available literature; it significantly differed from the position of the curves obtained with a correction coefficient of 0.95. The causes accounting for the systematic inaccuracy and erroneous values of the correction coefficients in earlier studies are discussed.

[Correction of the alkylnitrite method for the measurement of ethanol in blood: direct experimental evidence].

A coefficient (multiplier) for the correction of a systemic inaccuracy of ethanol detection in the blood by the alkylnitrite method arising from calibration against an aqueous solution has been improved. The experiment was carried out as a multilaboratory study (with the participation of six laboratories). The value of the coefficient was estimated at 0.82 +/- 0.014 (SD) instead of 0.95 computed earlier (CV = 1.7%). The main factor influencing the value of the coefficient turned out to be the time of preparation of the model ethanol-blood mixture for comparison with the aqueous solution. The coefficient of 0.82 was obtained using fresh blood samples that of 0.93 to 0.96 with blood samples previously stored during 3-10 days. The results of the study suggest different ethanol distribution patterns in vivo and in vitro in the aqueous phase of the blood stored for a few days.

[Forensic chemical investigation of alcohol-containing liquids contained polyhexamethylene guanidine hydrochloride and diethylphthalate].

Alcoholism remains one of the main causes of premature death in the population of Russia. Hence, the importance of the problem of uncontrolled distribution and consumption of surrogate alcoholic products, such as alcohol-containing liquids of uncertain origin. The objective of the present study was to detect ethyl alcohol, polyhexamethylene guanidine hydrochloride, and diethylphthalate in disinfectant liquids, biological fluids and human tissues and to analyse qualitative and quantitative composition of these materials.

[Application of near-infrared spectroscopy for differential detection of neuroleptics, derivatives of benzamides].

A method is proposed for the detection of neuroleptics including benzamide derivatives, such as amisulpride, sulpiride, and tiapride with the use of spectroscopy in the near infrared region. The method may be used for the purpose of forensic medical examination and chemico-toxicological studies. Specifically, it allows three characteristics of benzamide derivatives to be identified that make possible reliable discrimination between them.

[Comparison of beta60, beta-slope elimination rates in different periods after alcohol intake].

Ethanol elimination rate, beta60, calculated from hourly measurements of alcohol concentration in blood after its acute intake at a dose of 0.8 g/kg body weight was compared with that after intake of 2 g/kg body weight (experiments 1 and 2 respectively). In the latter experiment, coefficients of variation (CV) of relative mean individual elimination rate proved to be practically equal (11 +/- 3%) for all subjects of the study group (men of different age). This value was significantly smaller than in either separate age group (young and adult men) included in experiment 1(18 +/- 5% and 29.9 + 9% respectively). For each man consuming alcohol at a dose of 0.8 g/kg body weight, ethanol elimination rates were also compared 20, 15, and 10 min after intake. Coefficients of variation in this experiment turned out to be significantly higher, viz. 39%, 60%, and 68% respectively. Similar variations of the ethanol elimination rate were observed in saliva (32-50%). Possible causes of these changes and differences as well as their practical implications are discussed in the context of reliability of forensic medical examination. It is concluded that calculation of individual elimination rate values should be made 60 min after intake of alcohol whereas values obtained within 20 min are unreliable.

[Ethanol elimination rate (beta60, beta-slope) in different age groups after intake of a moderate or high dose of alcohol].

Ethanol elimination rate (beta60) was measured in different age groups of men and women following its single intake at a dose of 0.8 g/kg body weight (experiment 1) and 2 g/kg (experiment 2). Samples of capillary blood were collected 20, 40, 60, 90, 120, and 300 min (experiment 1) or 360 min after the termination of the intake (experiment 2). The phase of alcohol elimination was deduced from the kinetic curve. Each alcohol dose was consumed during 1-2 minutes or 1-1.5 hours (experiments 1 and 2 respectively). The value of (beta60) in experiment 1 was estimated at 0.17 +/- 0.04 per thousand/hour in young men aged between 18-26 years, 0.22 per thousand/hour in adult men of 32-48 years, and 0.21 per thousand/hour in women aged between 19-41 years. The difference between alcohol elimination rates in young and adult men on the one hand and between young men and women on the other hand was statistically significant (p < 0.01 and p < 0.05 respectively). In the second experiment, ethanol elimination rate was practically identical in men of the above age groups (0.16 +/- 0. 02 per thousand/hour) and significantly higher than in 64-66 year-old men (0.14 +/- 0.03 per thousand/hour). The values of ethanol elimination rate in men of group 2 calculated by the Weedmark formula proved underestimated by 17 +/- 5% regardless of their age. Men of both age groups included in experiment 1 showed an alcohol excretion rate overestimated by 8 +/- 5% and 31 +/- 6% respectively compared with 10 +/- 7% in women. It is suggested that a single intake of alcohol may lead to an instantaneous rise in the hepatic concentration of ethanol unrelated to the consumed amount that however affects its metabolic rate. It is concluded that the duration of ethanol intake has greater effect on the rate of its elimination from the body than the amount of consumed alcohol, especially in alcohol-tolerant subjects.

[Fatal poisoning with the local anesthetic bupivacaine].

Lethal concentration of bupivacaine was determined based on the examination of a case of poisoning with this local anesthetic agent taken at a dose 5 times the normal value. This study is of special interest taking into consideration the lack of data on toxic and lethal doses of bupivacaine in splanchnic organs and tissues in the literature.

[Measurement of thallium content in human urine by atomic absorption spectrometry after acute poisoning].

The problem of poisoning with thallium-containing substances continues to be of current concern. According to the Bureau of Forensic Medical Examination, Moscow, specimens of biological materials from more than 20 victims of such poisoning were delivered for analysis in 2006. The total number of thallium poisoning episodes during the period since 1996 exceeded 50. Materials for thallium determination in biological fluids (human blood and urine) using flame atomic absorption spectrometry were prepared by dry mineralization of accurately weighed samples; acidic solutions of the products of mineralization were used for analysis. Due to peculiar kinetic features of thallium ion absorption in the gastro-intestinal tract, blood could not be used as a biological marker of poisoning. The level of thallium in urine samples was found to vary from 1.00 to 4,600 mcg/l (with the estimation of confidence intervals in each case). Results of chemical analysis correlated with pathological symptoms derived from the patients' discharge summaries and literature reports on dose-effect relationships. Based on these findings, practically all the examined cases were characterized as severe acute poisoning.

[Toxicological characteristic of neuroleptics--substituted benzamides].

At present in the medical practice the group of neuroleptics, substituted benzamides is widely used. According to literature data they cause acute intoxications under particular conditions. The group of substituted benzamides includes drugs such as amisulpride, tiapride, sulpiride and sultoprid. Substituted benzamides intake causes toxic actions: psychotropic and neurotoxic. The neuroleptic intoxication is an effect of overdosage, abuse and hypersensitization. Severe intoxications with drugs of this group may cause lethal outcome.

[Current approaches to analysis of narcotic drugs in biological substances].

A method of analysis of basic narcotic drugs in urine is described. It consists in isolation by solid phase extraction, derivation and identification by gas chromatography with mass-selective detector. The approaches applied in the above method can be used for analysis of narcotic drugs undetectable by preliminary investigations as well as for urine examination for pharmacological or other biologically active substances.