Forensic Toxicology and Illicit Drugs

Introduction
  • Peter Stockholm from Forensic Science South Australia provides an overview of the analysis of drugs and poisons in blood samples, emphasizing the complexities and importance of forensic toxicology.

  • The presentation encompasses forensic drug chemistry, toxicology principles, drug classification systems, historical perspectives on drug use and regulation, common illicit drugs encountered in forensic cases, and key aspects of forensic toxicology analysis and interpretation.

Forensic Drug Chemistry and Toxicology
  • Forensic drug chemistry involves the detection, identification, quantification, and interpretation of drugs in seized materials, such as powders, tablets, or plant matter.

    • Detection involves using screening techniques to identify the possible presence of controlled substances.

    • Identification requires rigorous analytical methods to confirm the identity of the detected substance.

    • Quantification determines the amount of each controlled substance present in the sample.

    • Interpretation involves comparing the identified substances and their quantities to relevant legislation to determine legal implications.

  • Forensic toxicology applies these same principles to biological samples, such as blood, urine, or tissues, to determine the presence and concentration of drugs and poisons.

  • Unambiguous identification is critical for admissibility in court, necessitating the use of sophisticated instrumentation and validated analytical methods to ensure the accuracy and reliability of results.

  • Quantification plays a vital role in both forensic drug chemistry and toxicology.

    • In forensic drug chemistry, it determines the amount of a controlled substance in seized material, which is essential for legal purposes.

    • In forensic toxicology, drug concentration is measured to assess its potential effects on an individual's performance, to identify potential overdose situations, or to monitor medication adherence in clinical or forensic settings.

  • Interpretation is a critical step in both disciplines.

    • In forensic chemistry, the interpretation involves comparing the detected drugs against relevant legislation to determine if the possession, sale, or manufacture of the substance is illegal.

    • In forensic toxicology, the interpretation involves assessing drug concentrations in the context of various factors, such as the individual's medical history, tolerance, and the presence of other substances, to determine whether the drug levels are toxic, therapeutic, or lethal.

Forensic Drug Chemistry
  • Forensic drug chemistry focuses on the analysis of seized substances to identify and quantify controlled substances.

    • Examples include the analysis of synthetic cannabis products to determine the presence and concentration of synthetic cannabinoids, and the analysis of methamphetamine samples to determine their purity and composition.

  • Clandestine laboratories, particularly those involved in the production of methamphetamine, represent a significant global challenge due to the dangerous conditions and environmental hazards associated with their operation.

  • Chemists working in these environments wear protective gear to minimize exposure to toxic substances and maintain safety.

  • A rise in the prevalence of synthetic benzodiazepines and novel psychoactive substances (NPS) has been observed in recent years.

    • These substances, which are often designed to mimic the effects of traditional illicit drugs, pose analytical challenges due to their structural diversity and limited availability of reference standards.

    • The increasing prevalence of NPS is a growing concern in South Australia and Australia in general, requiring ongoing monitoring and adaptation of analytical techniques.

Forensic Toxicology
  • Forensic toxicology centers on the analysis of biological specimens to detect and quantify drugs, poisons, and other toxic substances.

    • Common specimens include liver tissue, urine, blood samples, and vitreous humor obtained during autopsy.

  • Challenges in forensic toxicology include the analysis of very low drug concentrations, particularly in cases involving chronic drug use or delayed sample collection.

  • Forensic toxicologists are tasked with detecting both illicit and prescription drugs in biological samples to provide a comprehensive assessment of drug exposure.

  • The primary aims of forensic toxicology are to determine the cause of death in cases of suspected poisoning or drug overdose, and to assess a person's condition or impairment during an incident, such as a traffic accident or assault.

Drug Classification
  • Drug classification is essential for organizing and understanding the diverse range of substances encountered in forensic toxicology.

    • Broad chemical properties: Drugs can be classified based on their chemical nature as acidic, basic, or neutral, which influences their behavior in biological systems and extraction techniques.

    • Therapeutic class/action: Drugs can also be classified based on their effects on the body or their mechanisms of action, such as antidepressants, stimulants, or their interaction with specific receptors (e.g., opioids).

    • Legislation: Legal classifications categorize drugs based on their restricted or prohibited status, reflecting societal concerns and regulatory efforts to control their availability and use.

  • Acidic vs. Basic Drugs

    • Basic drugs typically contain an amine group (RNH2) in their chemical structure.

    • Amphetamine, a stimulant drug, serves as an example of a basic drug with an amine group.

    • Acidic drugs, on the other hand, possess a carboxyl group (COOH) in their structure.

    • GHB, a central nervous system depressant, exemplifies an acidic drug with a CO2H group.

    • The acidic or basic properties of drugs influence their extraction from biological materials.

    • By adjusting the pH of the sample and using organic solvents, forensic toxicologists can selectively extract drugs based on their acid-base properties.

    • Neutral drugs lack active hydrogen atoms in their structures.

    • These drugs can be extracted under both acidic and basic conditions due to their neutral charge.

  • pKapKa is the concentration at which there are equal numbers of charged and uncharged molecules.

  • Drugs can be separated into acidic or basic classes based on their chemical structures.

  • Therapeutic Classification

    • Therapeutic classification categorizes drugs based on their effects on the body and their mechanisms of action on specific receptors.

    • Examples include antidepressants, which alleviate symptoms of depression; stimulants, which increase alertness and energy; sedatives, which induce relaxation and sleep; and analgesics, which relieve pain.

    • Opioids exert their effects by acting on mu opioid receptors in the brain and spinal cord, modulating pain perception and producing euphoria.

    • Cannabinoids interact with CBD receptors in the endocannabinoid system, influencing various physiological processes such as mood, appetite, and pain sensation.

  • Legislation classification

    • Legislation classification reflects societal attitudes and priorities regarding drug regulation, with legal and illegal drugs determined by community values.

    • In South Australia, the Controlled Substances Act governs drug classification and regulation.

    • The act has been updated since its original inception in 1984 to adapt to changing drug trends and emerging public health concerns.

    • Regulations provide flexibility for easier updates compared to amending the act itself, allowing for timely responses to new drugs and evolving drug-related issues.

    • Australia maintains a harmonized agreement for drug classification through the Standard for the Uniform Scheduling of Medicines and Poisons (SUSMP).

    • Medicines are assigned schedules (e.g., S2 pharmacy medicine, S4 prescription medicine) based on their risk profile and availability to the public.

    • S8 drugs are classified as drugs of dependence (e.g., morphine) due to their potential for abuse and addiction.

    • S9 drugs are prohibited substances with no recognized medical use (e.g., heroin, cocaine, LSD) and are subject to strict legal controls.

    • New psychoactive substances are often scheduled in the S9 class due to their unknown pharmacological effects and potential for harm.

The Importance of Drug Regulation
  • Regulation is primarily for safety, not just tax revenue or control.

  • Drugs interact with receptors, affecting developing bodies.

  • Risks include psychological harm, physical harm, and societal harm due to addiction.

Historical Context
  • Paracelsus: Dose determines if a substance is a poison.

  • Fellows Compound Syrup: Contained strychnine hydrochloride.

    • A spoonful taken daily before meals was considered a tonic.

    • Labeled as poison to comply with the poison's act.

  • Many current prohibited substances were common in the late 1890s.

    • Foldings: Sold coca wine.

    • Sepulks: Sold Sedna (coca wine, cola wine, port wine, and beef wine).

  • Heroin was once freely available for medicinal purposes.

  • Advertisements in the 1940s promoted amphetamines for fitness and weight loss.

  • Cocaine was used as an anesthetic for sore throats and toothaches.

  • Chloridyne: Contained morphine, chloroform, cannabis, and hydrocyanic acid.

    • Used for diarrhea, dysentery, cholera, fever, neuralgia, and cramps.

    • Addiction and deaths associated with Chloridyne due to high morphine content were common.

Common Illicit Drugs
  • Methamphetamine, cannabis (THC), and MDMA are common.

    • Detected in 21% of drivers/riders killed in road accidents.

  • GHB is prevalent, particularly in Adelaide.

  • Cocaine is less common in Adelaide compared to other states.

  • Opiates are consistently present.

  • New psychoactive substances (NPS): Chemical analogs of old drugs.

    • Slightly altered structures to bypass legal restrictions.

    • Often based on failed pharmaceuticals.

Study Results in Adelaide
  • Emergency department patients with drug intoxication symptoms were sampled.

  • 50% tested positive for methamphetamine.

  • Alcohol and GHB were also common.

  • Flualprazolam and etizolam (NPS) were detected.

  • Most cases involved multiple drugs (average 2.9 drugs per person, up to 9 drugs in some cases).

  • 95% of GHB users also used methamphetamine.

Illicit Drug Examples
  • Methamphetamine, MDMA pills, cannabis.

  • Roadside drug testing devices used by police.

  • Drug driving is a significant problem.

    • Oral fluid samples sent to Forensic Science SA for analysis.

    • 97% accuracy at the roadside.

Opioids and Opiates
  • Morphine (S8), codeine (S4), heroin (S9).

    • Heroin's structure is similar to morphine with two acetyl groups.

  • Oxycodone is another opiate.

  • Opioids have similar effects due to molecular conformation.

  • Emerging opioid NPS: AH-7921, U47700, and Ocfentanil.

    • Developed in pharmaceutical trials in the 80s and 90s but never produced.

GHB (Gamma-Hydroxybutyrate)
  • Causes euphoria, hypnosis, amnesia, drowsiness, and central nervous system/respiratory depression.

  • GHB is an S9 drug.

  • Butanediol (1,4-B) and gamma-butyrolactone (GBL) are converted to GHB in the body.

    • Butanediol gets converted to GHB through the same process that you metabolize alcohol.

    • One of the hydroxyl groups gets acted on by alcohol dehydrogenase, and you end up with an aldehyde, and then acetaldehyde dehydrogenase turns it into GHB.

  • 1,4 Butanediol is an industrial solvent that the sale of is starting to get restricted because it is being used as a precursor for GHB.

  • Beados Example: 02/2007: Manufacturer shifted from 1,5 pentanediol to 1,4 butanediol.

    • 1,4 Butanediol is sweet, resulting in kids eating the sweet tasting alcohol and becoming intoxicated.

New Psychoactive Substances (NPS)
  • Since 2010, approximately 1500 new drugs have emerged.

  • Pose challenges for analysis, law enforcement, and harm reduction.

  • Purity is often very high, leading to unpredictable effects.

Forensic Toxicology: Detection, Quantification, and Interpretation
  • Sample types depend on the case.

    • Coronial: Blood, urine, liver, vitreous humor.

    • Purpose: Determine if drugs contributed to death or lack of medication.

    • Drugs of interest: Alcohol, prescription drugs, illicit drugs, pesticides, poisons.

    • Police: Urine or blood from suspects/victims.

    • Purpose: Drug-facilitated assault, crimes.

    • Drugs of interest: Alcohol, sedatives, prescription drugs, illicit substances.

    • Traffic: Blood/oral fluid to assess impairment.

    • Drugs of interest: Methamphetamine, THC, MDMA.

    • Mandatory blood samples after vehicle accidents in South Australia.

  • Detection Methods

    • Sample preparation: Protein precipitation, liquid-liquid extraction, and solid-phase extraction.

    • Each of which transform the sample into a suitable form for testing

    • Instrumentation: Chromatography and mass spectrometry.

    • Chromatography separates mixtures into components through the use of a column.

    • Mass spectrometry identifies characteristic fragments.

  • Liquid Chromatography (LC MS)

    • LC QTOF (quadrupole time of flight mass spec) provides accurate mass measurement.

    • A lot of data is measured such as the retsention time and the mass spectrum.

  • Gas Chromatography (GC)

    • Used widely in illicit drug chemistry for samples with high concentrations.

    • Sample is injected into a column that is made of very thin tubing approximately 50-100 meters long to then be pushed through by gas.

    • GC is used to determine what things are.

    • Comparison can be made to compare clozapine in a sample to that of a library.

Interpretation of Results
  • Determines if drug levels were therapeutic, toxic, or lethal.

  • Requires specialists (pharmacologists or forensic pathologists).

  • Postmortem concentrations may differ from levels when alive.

  • Drug interactions complicate interpretation (e.g., alcohol + benzodiazepines).

  • Tolerance affects drug effects.

  • Pharmacologists provide opinions on effects and interactions.

  • Analytical toxicologists offer general interpretations.

Conclusion
  • Overview of illicit drugs and forensic toxicology.

  • Further information: Contact Peter Stockholm via email or listen to the Tox Pod podcast.