5. analytic and forensic toxicology

Toxicology

1. Bule Hora University College of Health and Medical Sciences Department Of Pharmacy TOXICOLOGY For 4 th year Medical Laboratoy Students Principle of Analytic Toxicology 1 By:Aliyi G.( B.Pharm)

2. 2 5.Principles of Analytic Toxicology . Applications in general and forensic toxicology and clinical practice . Interpretation of analytic results Principle of Analytic Toxicology

3. 3 Analytic Toxicology The detection , identification & measurement of foreign compounds (xenobiotics) in biological & related specimens. Involves application of the tools of analytic chemistry to the qualitative or quantitative estimations of chemicals that may exert adverse effects on living organisms. is the only means by which objective evidence of the nature & magnitude of exposure to a particular compound or a group of compounds can be made. 1. Introduction Principle of Analytic Toxicology

4. Introduction Cont’d,... 4 Forensic Toxicology The use of toxicology for purposes of the law . To identify any chemical that may serve as a causative agent in inflicting death or i njury/damage on humans/property . Principle of Analytic Toxicology

5. Introduction Cont’d,... 5 Separation is more often a prerequisite for analytical determination. Gases Volatile Substances Corrosive Agents Metals Anions and Nonmetals Nonvolatile Organic Substances Miscellaneous Principle of Analytic Toxicology

6. Application of Analytic Toxicology 6 Principle of Analytic Toxicology

7. 1. Role in General Toxicology 7 Ascertaining purity of a chemical or contaminants of chemical to be studied The chemical under study must be pure or the nature of any contaminant must be known to interpret experimental results with validity. Monitorin g dosage forms or solutions for stability throughout the course of an experimental study. Important in establishing the bioavailabilit y of a compound under study Rather than observing dose-effect r/n ships , more accurate to describe blood (serum) conc -effect r/n ship. Principle of Analytic Toxicology

8. 2. Analytic Role in Clinical Toxicology 8 Used to identify the nature of the toxic exposure and measure the amount of the toxic substance that has been absorbed. monitoring the amount of the toxic agent remaining in circulation or measuring what is excreted. Important in establishing a diagnosis of poisoning & guiding treatment Principle of Analytic Toxicology

9. Importance 9 Both the identity/nature & amount of toxic s/ ce – aid in diagnosis, t/t, monitoring the effectiveness of t/t regimens. Nature & amount coupled by information on the clinical state permits to relate the signs & symptoms observed to the anticipated effects of the toxic agent. Principle of Analytic Toxicology

10. Most commonly encountered drugs & methods for analysis in emergency toxicology Rank Drug Specimen Analytical method 1 Drugs of abuse urine immunoassays 2 ethanol serum GC 3 benzodiazepins Urine/serum Immunoassay or GC 10 Principle of Analytic Toxicology

11. 3. Analytic Role in Therapeutic Monitoring 11 Factors responsible for individual variability in responses to drug therapy include: Rate and extent of drug absorption Distribution and binding in body tissues and fluids Rate of metabolism and excretion Pathologic conditions Interaction with other drugs Monitoring of the plasma or serum conc . at regular intervals will detect deviations & suggest that one or more of these of variables need to be identified & corrected. Principle of Analytic Toxicology

12. 4. Analytic Role in Biologic Monitoring 12 Monitor workers directly for exposure Exposures are to a mixture of compounds. Measure changes of normal metabolites induced by xenobiotics. eg. the profile of glucouronic acid metabolites excreted in urine can be altered after exposure to substance that induce monoxygenase activity.. Principle of Analytic Toxicology

13. 5. Role in Forensic Toxicology 13 Postmortem Investigations Qualitative & quantitative analysis of drugs/poisons in biological specimen collected. + Interpretation of analytic finding in regard to physiologic & behavioral effects. NB: many drugs or poisons do not produce characteristic pathologic lesions; their presence in the body can be demonstrated only by chemical method of isolation & identification Principle of Analytic Toxicology

14. Application of forensic toxicology 14 Principle of Analytic Toxicology

15. Application of forensic toxicology Cause of death in poisoning cases . Assist in cause of death for a court of law. Presence of intoxicating concentration of ethanol in car accidents. Carbon Monoxide detection in fire victims. Provide data for substance abuse. Principle of Analytic Toxicology 15

16. 1. Toxicological Investigation of a Poison Death 16 3 steps Obtaining case history and suitable specimens Toxicologic analyses Interpretation of Analytic findings Principle of Analytic Toxicology

17. 1.1. Case History and Specimens 17 Collect facts (age, sex, wt, medical history, occupation, t/t administered before death). Gross autopsy findings. Drugs available to the decedent. Interva l between the onset of symptoms and death. Principle of Analytic Toxicology

18. 1.2. Toxicologic Analyses 18 Factors to consider Amount of specimen available Nature of the poison Possible biotransformation of the poison Eg.cocaine. Principle of Analytic Toxicology

19. Toxicologic Analyses… 19 In case of involving oral administration of the poison Organs Analyzed 1 st Gastrointestinal contents (residual unabsorbed poison found ) 2 nd Urine (high conc. of toxic s/b &its metabolites) Liver….1 st internal organ analyzed Specific poison is suspected to have caused or contributed to a death, the tissue & fluids in which the poison concentrates Principle of Analytic Toxicology

20. Toxicologic Analyses… 20 The analysis (the autopsy & toxicological) should be started soon after death. Problems: Hydrolysis, oxidation or reduction of proteins, nucleic acids, or lipids that may generate compounds that interfere with identification. Principle of Analytic Toxicology

21. Toxicologic Analyses… 21 Testing Non-specific test Ferric chloride, perchloric and nitric acid color test for phenothiazine drugs and immunoassays for the detection of amphetamines, benzodiazepines and opiates in the urine. Specific test GC or HPLC is most widely used for most drug identification. Principle of Analytic Toxicology

22. 1.3. Interpretation of Analytic Results 22 Provides answers Route of Administration Dosage and if conc. of toxicant present is enough to cause death or alter action enough to cause death. Tests on blood, tissue, and plasma Results are often used to corroborate investigative findings Eg . Continuously elevated hair arsenic values indicates chronic rather than acute poisoning as the cause of death. Principle of Analytic Toxicology

23. Interpretation of Analytic Results … 23 A new extension of forensic toxicology is the analysis of impurities of illicit drug synthesis in biological specimens. Eg. Methamphetamine Principle of Analytic Toxicology

24. 2. Criminal Poisoning of the Living 24 GC or HPLC tests are used for 2 types of poisoning Administration of drugs to incapacitate victims of kidnapping, robbery, or sexual assault. Eg . Ethanol, BDZ , marijuana, amphetamine, opaites etc Poisoning as a form of child abuse ; deliberate administration of toxic or injurious substances to a child , usually by a parent or other caregiver Eg . Syrup of ipecac, table salt, laxative, diuretics, narcotics etc Principle of Analytic Toxicology

25. 3.Forensic Urine Drug Testing 25 Urine tested for a limited number of drugs. Sample is checked for adulteration by checking the pH, creatine, specific gravity and for any unusual color or smell. Principle of Analytic Toxicology

26. Forensic Urine Drug Testing… 26 There may be valid reasons other than substance abuse for positive drug findings eg . Poppy seed ( papaver somniferum ) is common ingredeint in many pastries & breads. poppy seeds may contain significant amounts of morphine. Morphine is a major metabolites of heroin , to readily differentiate heroin abuse from poppy seed ingestion, analysis may be performed for 6-monoacetylmorphine a unique heroin metabolite . Principle of Analytic Toxicology

27. 4. Human Performance Testing 27 Tests for ethanol and chemicals in blood, breath or other specimens that may modify performance of behavior. Alcohol related accidents are responsible for 55-65% of fatalities in drivers Principle of Analytic Toxicology

28. 5. Courtroom Testimony Lay(uncertified) witness Vs expert witness Toxicologist an expert witness providing an objective testimony and opinion . Objective~ Involves description of his or her analytic methods and findings Opinion~how the person interprets the results . Principle of Analytic Toxicology 28

29. Thank you!!! Principle of Analytic Toxicology 29