Toxicology

1. BULE HORA UNIVERSITY
COLLEGE OF HEALTH AND MEDICAL
SCIENCES
DEPARTMENT OF PHARMACY
TOXICOLOGY
For 4th 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
1. Introduction
Principle of Analytic Toxicology

4. Introduction Cont’d,...
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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 injury/damage
on humans/property.
Principle of Analytic Toxicology

5. Introduction Cont’d,...
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 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
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Principle of Analytic Toxicology

7. 1. Role in General Toxicology
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 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.
 Monitoring dosage forms or solutions for stability throughout the
course of an experimental study.
 Important in establishing the bioavailability of a compound under
study
 Rather than observing dose-effect r/n ships ,
Principle of Analytic Toxicology

8. 2. Analytic Role in Clinical Toxicology
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 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
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 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
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Principle of Analytic Toxicology

11. 3. Analytic Role in Therapeutic Monitoring
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 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
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 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
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 Postmortem Investigations
 Qualitative & quantitative analysis of drugs/poisons
in biological specimen collected.
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 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
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Principle of Analytic Toxicology

15. Application of forensic toxicology
Cause of death in .
 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
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16. 1. Toxicological Investigation of a Poison Death
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 3 steps
1. Obtaining case history and suitable specimens
2. Toxicologic analyses
3. Interpretation of Analytic findings
Principle of Analytic Toxicology

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

18. 1.2. Toxicologic Analyses
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 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…
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 In case of involving oral administration of the poison
 Organs Analyzed
1st Gastrointestinal contents (residual unabsorbed
poison found )
2nd Urine (high conc. of toxic s/b &its metabolites)
Liver….1st 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…
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 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…
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 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
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 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
Principle of Analytic Toxicology

23. Interpretation of Analytic Results…
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 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
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 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
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 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…
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 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-
Principle of Analytic Toxicology

27. 4. Human Performance Testing
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 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
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