Lecture
A steady increase in the number of poisonings, especially those caused by medicinal drugs, has been observed in recent times in all developed countries of the world. The growth in the number of poisonings is significantly influenced by environmental pollution from industrial waste and the accumulation of large amounts of toxic waste, which under certain conditions becomes a cause of poisoning. Toxicological chemistry arose from the needs of toxicology, which is reflected both in its name and in the content of the subject. The name toxicology comes from two Greek words, toxicon (poison) and logos (science, study) – that is, toxicology – is the science of poisons and their action on the body (of humans, animals, or plants).
The relationship of toxicological chemistry to other sciences. In the modern understanding, toxicological chemistry – is the science of the chemical methods of isolating, detecting, and determining poisonous and potent substances, as well as the products of their transformation in the tissues, organs, and fluids of the body and in environmental objects (water, air, food residues, medicines, etc.). Toxicological chemistry is a pharmaceutical discipline and is closely related to medical sciences (toxicology, pharmacology), biological sciences (biochemistry, pharmacognosy), and chemical sciences (analytical, organic, physical, and pharmaceutical chemistry).
The main objectives of toxicological chemistry
- The development of new methods and the improvement of methods already used for sample preparation, purification, identification, and quantitative determination of poisonous and potent substances in biological objects (post-mortem material and biological fluids from living persons), as well as in environmental objects.
- The study of the possibilities of isolating, detecting, and determining the transformation products of toxic substances in the living body and in the corpse.
Every year, chemical-toxicological studies carried out by specialized institutions in the performance of forensic medical, clinical toxicological, criminalistic, anti-doping, ecological, and other examinations are becoming increasingly relevant.
In performing the examinations listed, specialized services in practice solve the same tasks and in their work use a methodology of chemical-toxicological analysis (CTA) that is common to all, including the rules for sample collection,
methods for isolating chemical substances (toxicants) from objects
of examination, their identification and quantitative determination, and the interpretation of the results obtained, with the specific features involved for
each type of examination.
By means of CTA methods, analytical toxicology (toxicological chemistry) solves a number of applied and preventive problems. Indeed, with the help of CTA methods:
• the causes of poisoning are established;
• the biotransformation (metabolic pathways)
of toxicants is studied;
• the toxic and lethal doses of toxicants are determined;
• the maximum allowable
concentrations of toxic substances in water and air are established and monitored;
• residual amounts of pesticides and toxic
substances in food products are regulated;
• the states of alcohol and substance-induced
intoxication, etc. are determined.
In light of current views, in most developed countries
toxicological chemistry is called analytical toxicology.
In the opinion of many specialists, this latter name of the discipline more fully
reflects the purpose, objectives, and directions of application of CTA.
Analytical toxicology develops methods of chemical-toxicological analysis of xenobiotics, used for their determination in objects of various nature.
The following objects of CTA are defined:
• of biological origin: post-mortem or autopsy material
(liver, kidneys, lungs, brain, spleen, etc.), biological fluids (blood, urine, bile, saliva, sweat secretions, etc.);
• of non-biological origin: physical evidence (objects seized from the scene: powders, solutions, tablets, dishware, containers or syringes containing trace amounts of toxicants, dried
residues of solutions, plant material, for example, cannabis samples,
etc.), water, soil, food products, etc.
Analytical toxicology is an applied discipline
that is based on fundamental sciences and other applied
disciplines: general chemistry, inorganic chemistry, organic chemistry,
analytical chemistry, pharmacology, pharmacognosy, ecology, forensic
medicine, and others, with which it shares either a common subject of study (research), for example, chemical substances, or common research methods. In addition to CTA methods, analytical toxicology also
addresses questions of the biotransformation of toxicants and the mechanisms of their toxic action on the body, which, in turn, are studied on the basis of
such fundamental sciences as biological chemistry and toxicology.
The main goal of analytical toxicology is the development of methods
of sample preparation (isolation, purification, concentration), detection, identification, and quantitative determination of xenobiotics in biological and other objects of chemical-toxicological examination.
The main objectives of analytical toxicology:
1) the development and improvement of methods for isolating toxicants and their metabolites from biological objects;
2) the development and improvement of methods for purifying isolates
of toxicants and their metabolites from biological objects, removing impurities
of various natures;
3) the development of sensitive and selective methods for the detection, identification, and quantitative determination of toxicants and their
metabolites in extracts obtained from biological
objects;
4) the development of new analytical methods for the analytical diagnosis of alcohol, narcotic, and substance-induced intoxication;
5) the development and improvement of methods for analyzing physical evidence for the content of narcotic, psychoactive, potent, and other toxic substances;
6) the development of rapid methods for analyzing biological fluids for
analytical diagnosis of acute poisoning and choice of appropriate
detoxification methods;
7) development of new methods of analysis for the sanitary-hygienic
examination of the environment and food.
Mastering the fundamentals of analytical toxicology, together with certain
theoretical knowledge and practical skills in chemical-toxicological analysis (CTA), is necessary for a pharmacist to understand the toxic action of many chemical substances, including medicinal products, the methods of detoxifying the body in acute poisoning, and subsequent specialization
in forensic medical and sanitary-hygienic examination, clinical toxicology, addiction medicine, criminalistics, ecology, etc.
The development of chemistry contributed to the emergence of scientific forensic-chemical research. In the time of M.V. Lomonosov, the duties of a staff pharmacist included the detection of poisons.
Stages:
Before the Common Era, the earliest information on the use of animal and plant poisons for treating those wounded in war or hunting can be found in ancient manuscripts. One such document contains information on the use of opium, and compounds of lead, copper and antimony.
1st century CE – the military physician Dioscorides attempted to classify poisons, dividing them into animal, plant and mineral.
The early and developed Middle Ages (5th–15th centuries). In Baghdad in 758, the first pharmacy opened, and alchemists of the East invented the water bath and the distillation still, and obtained nitric and hydrochloric acids, bleaching powder and alcohol.
The late Middle Ages (end of the 14th, beginning of the 15th century) – the wife of the King of France, Catherine, supervised the preparation of poisonous mixtures, recording the moment the toxic effect appeared. Paracelsus developed his own classification of diseases and factors affecting human health. «Everything is poison, and nothing is without poison; only the dose makes a thing not a poison» Paracelsus
18th century – professional toxicology develops.
19th century – Louis Lewin published works on the toxicity of narcotic substances, methanol, acrolein, glycerin and chloroform. Claude Bernard discovered the mechanism of action of poison. In Russia: A.P. Nelyubin described a mineralization method for determining metallic poisons, and arsenic by reducing it to arsine.
20th century – in 1938 a mass poisoning by sulfanilamide preparations was registered in the USA, and in connection with this an agency for the control of medicines was created.
A great contribution to modern toxicological chemistry was made by the authors of textbooks Stepanov, Shvaikova, Kramarenko. Clinical toxicology in Russia was developed thanks to the RAMS (Russian Academy of Medical Sciences).
Biochemical toxicology studies the toxicodynamics and toxicokinetics of xenobiotics and their metabolites, the mechanisms of formation of the toxic effect in the toxicant–receptor system, and the rates and mechanisms of intake, distribution, biotransformation, elimination, and excretion of toxicants and their metabolites.
Analytical toxicology – develops methods of analysis for determining toxicants in various objects. In doing so, great attention is paid to preparation of the object for analysis (sample preparation). Sample preparation consists in the isolation of the xenobiotic from the object under analysis and its concentration in the sample. For example, determination of toxic substances in biofluids (urine, blood, saliva, cerebrospinal fluid), organs and tissues (liver, kidneys, skin, hair, nails), vomitus, etc., in drug residues, in food. Depending on the nature of the toxic substance and the biomaterial, extraction, distillation, dialysis, mineralization, and microdiffusion are used for isolation.
Timely solution of these problems makes it possible to determine the cause of poisoning and to render rapid assistance. Clinical diagnosis makes it possible to determine the direction of the search for the toxicant. As a result of chemical-toxicological investigation it becomes possible to determine the substance or group of substances that caused the poisoning, to carry out diagnosis, to determine the phase of poisoning, and to carry out detoxification effectively. Chemical-toxicological investigation must be carried out within the shortest possible time, since poisoning, being a disease of chemical etiology, requires urgent therapy.
The main directions of analytical toxicology:
1. Forensic-toxicological – carrying out forensic medical
examination for the purpose of establishing the cause of fatal poisoning
by a chemical substance.
2. Clinical-toxicological – analytical diagnosis of acute
poisoning by chemical substances.
3. Narcological – determination of the degree of alcohol
intoxication, as well as the fact of use of narcotic and psychoactive substances.
4. Ecotoxicological – determination of the concentration of toxicants in the environment (soil, water, air), in industrial work zones,
food products and other objects.
Forensic medical examination is the application of forensic medical knowledge to resolve questions arising in the practical
activity of the bodies of inquiry, investigation and the court. An examination, in
particular a forensic medical one, is one of the forms of evidence in the investigative and judicial
proceedings.
The overwhelming majority of examinations are carried out by forensic medical experts, that is, physicians who have received special training and hold the positions of forensic medical experts. Thus
the examination is an official, state examination. The duties of a forensic medical expert may be performed only by a specialist with a higher
medical education. If there is no physician holding the position
of forensic medical expert, then in accordance with Art. 192 of the Code of Criminal Procedure of Ukraine, a physician of another specialty is invited. In this case
he is called an expert physician, and the rights
and duties of a forensic medical expert extend to him. This type of examination is called a free examination.
The conduct of forensic medical examination is regulated
by separate special articles of the Criminal Code (CC),
the Code of Criminal Procedure (CCP), the Civil Code (CivC), the Code of Civil Procedure (CCP) of Ukraine,
resolutions and orders of the government, as well as by regulations, rules and instructions approved by the Ministry of Health of Ukraine.
Forensic medical examination (investigation), like other types of
examination, is carried out only by written order,
resolution, or submission of the bodies of inquiry, the investigative authorities, or by ruling of the court (Art. 196 of the Code of Criminal Procedure of the RF). In accordance with Art. 76 of the Code of Criminal Procedure of
Ukraine it is mandatorily ordered to establish the cause and category of death; the nature and severity of bodily injuries;
sexual maturity in cases of crimes provided for in Art. 120 of the Code of Criminal Procedure
of Ukraine; the age of the suspect or accused, if this is
relevant for deciding the question of their criminal liability in the absence of the corresponding documents on age.
Forensic medical examination is carried out both at the preliminary investigation stage and at the court hearing
The objects of forensic medical examination may be:
• victims, accused, and other persons (living persons);
• the bodies of persons who died a violent death as a result of murder, suicide or accident, or on suspicion
of such a death; persons who died suddenly in medical institutions
with an unestablished diagnosis during the first day of their stay there; unidentified persons; persons who died in medical institutions, in the case of
a complaint by relatives to the prosecutor's office about improper treatment
of the patient; newborns on suspicion of their murder, etc.;
• physical evidence – objects or traces that may serve
to reveal the circumstances of the case, to establish or refute a criminal act, and to reveal the essence of what occurred. The procedural definition of physical evidence is given in Art. 78 of the Code of Criminal Procedure of the RF.
Physical evidence may consist of a wide variety of objects.
Most often, in forensic medical practice, objects are examined
bearing traces of blood, hair, semen, saliva, fragments of bones, internal organs, that is, physical evidence of biological origin;
• materials of criminal and civil cases. A significant
object of examination may be case materials, when the investigator or
the court sends the expert the entire case for study and to answer
the questions posed. This is applied in those cases where
the case contains many various medical documents, or several
conflicting expert conclusions or examinations that diverge from the data of the investigation, etc.
Without exception, all objects are examined upon the ordering of an examination only by resolution of the person conducting the inquiry,
the investigator, the prosecutor, or by ruling of the court. The examination of each
object is carried out in accordance with special instructions, methodological guidelines, and rules approved by the Ministry of Health of Ukraine. In the conduct of forensic medical examinations there must be a unified organizational basis, ensuring, on the one hand, that experts comply
with the requirements of the law, and on the other – that the examination is carried out using scientifically substantiated methods of investigation. Of such
importance are the instructional-methodological materials currently in force in the system of forensic medical examination.
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