Forensic Toxicology and Illicit Drugs Notes

## Introduction - Peter Stockholm from Forensic Science South Australia discusses the analysis of drugs and poisons in blood samples. - Overview of forensic drug chemistry, toxicology, drug classification, historical remedies, common illicit drugs, and forensic toxicology aspects. ## Forensic Drug Chemistry and Toxicology - Detection, identification, quantification, and interpretation of drugs. This involves a comprehensive understanding of chemical structures, reactions, and instrumental analysis techniques. - Applies to seized materials (forensic drug chemistry) and biological samples (forensic toxicology). Forensic drug chemistry focuses on analyzing substances seized by law enforcement, while forensic toxicology deals with analyzing drugs and poisons in biological samples from individuals. - Unambiguous identification is crucial for court admissibility, requiring sophisticated instrumentation. Techniques such as mass spectrometry, nuclear magnetic resonance (NMR), and infrared spectroscopy are utilized to ensure accurate identification. - Quantification is essential to determine the amount of substance present. - Forensic chemists determine the amount of controlled substance. Accurate quantification is vital for legal purposes and helps in understanding the scale of drug-related crimes. - Forensic toxicologists assess drug effects on performance, overdoses, or medication adherence. This assessment aids in determining the role of drugs in impairment, toxicity, or compliance with prescribed medication regimens. - Interpretation involves relating drug detections to legislation (chemistry) or determining toxic, therapeutic, or lethal concentrations (toxicology). This step requires a thorough understanding of pharmacology, toxicology, and relevant legal frameworks to provide meaningful conclusions. ## Forensic Drug Chemistry - Deals with seized substance analysis. This includes a wide range of substances, from illicit drugs to counterfeit medications. - Examples include synthetic cannabis and large methamphetamine seizures. Synthetic cannabis poses unique challenges due to the constantly evolving chemical structures, while methamphetamine seizures often involve large quantities and complex manufacturing processes. - Clandestine laboratories pose significant dangers due to toxic chemicals and unsafe conditions. These labs often lack proper ventilation and safety equipment, leading to explosions, chemical spills, and exposure to hazardous substances. - Chemists require sophisticated protective gear. This includes respirators, Tyvek suits, gloves, and eye protection to minimize exposure to toxic chemicals. - Rise in synthetic benzodiazepines and novel psychoactive substances (NPS) is a growing concern. These substances are often designed to mimic the effects of traditional drugs but with different chemical structures, making them difficult to detect and regulate. ## Forensic Toxicology - Involves trace analysis in biological specimens. This requires highly sensitive analytical techniques to detect and quantify drugs and poisons in complex matrices such as blood, urine, and tissues. - Challenges include analyzing low concentrations of drugs in various samples (liver, urine, blood, etc.). Factors such as metabolism, degradation, and distribution can affect drug concentrations in different tissues and fluids. - Focus extends beyond illicit drugs to include prescription drugs. Prescription drug abuse is a significant concern, and forensic toxicologists play a crucial role in detecting and quantifying these substances in forensic samples. - Important for determining cause of death or condition during incidents. Forensic toxicology findings can provide valuable information for medical examiners and law enforcement in determining the circumstances surrounding a death or injury. ## Drug Classification - Classified by broad chemical properties (analytical toxicology), therapeutic class/action (clinical toxicology), or legislation. - **Chemical Properties:** - Acidic or basic drugs based on the presence of amine (basic) or carboxyl (acidic) groups. The chemical properties of drugs influence their behavior in biological systems and their detectability by analytical techniques. - Basic drugs have an amine group (RNH2), e.g., amphetamine. $RNH_2$ - Acidic drugs have a carboxyl group (COOH), e.g., GHB (Gamma-Hydroxybutyric acid). $COOH$ - Neutral drugs have no active hydrogen. - Exploiting pH differences allows extraction of drugs into solvents. Adjusting the pH of a solution can selectively protonate or deprotonate drugs, allowing them to be extracted into organic solvents. - pKa is the concentration at which there are equal numbers of charged and uncharged molecules. pKa values are important for predicting the behavior of drugs in different physiological compartments. - Drugs can be separated into acidic, basic, or neutral classes based on their chemical structure. This classification is useful for developing analytical methods and predicting drug behavior. - **Therapeutic Class/Action:** - Based on how the drug affects the body (antidepressant, stimulant, sedative, analgesic) - Or based on receptor action (opioid acts on mu-opioid receptor, cannabinoid acts on CBD receptors). Understanding the therapeutic class and receptor action of drugs is essential for interpreting their effects on behavior and physiology. - **Legislation:** - Classification based on community standards and legal restrictions. Regulatory agencies classify drugs based on their potential for abuse and harm, which determines their availability and restrictions. - Controlled Substances Act in South Australia and national scheduling (SUSMP) classify drugs. These legal frameworks aim to control the distribution and use of drugs to protect public health and safety. - S2: Pharmacy Medicine, S3: Pharmacist Only Medicine, S4: Prescription Only Medicine, S8: Controlled Drug (drugs of dependence like morphine, oxycodone, fentanyl), S9: Prohibited Substance (heroin, cocaine, LSD). ## Regulation of Substances - Regulation is primarily for safety due to drugs' interaction with receptors. Drugs can have profound effects on physiological and psychological functions due to their interactions with receptors in the body. - Aims to prevent psychological, physical, personal, and societal harm, including addiction. - Paracelsus: "The dose makes the poison." This principle highlights the importance of dose-response relationships in toxicology and pharmacology. - Fellows Compound Syrup contained strychnine hydrochloride as a tonic. This historical example illustrates the use of toxic substances in unregulated medicines. - Many prohibited substances were commonplace in the late 1890s. Historical context provides insights into changing attitudes and regulations regarding drug use. - Fouldings sold coca wine. - Sepulks sold Sedna (coca wine, cola wine, port wine, beef wine). - Heroin was used medicinally, with consumption doubling after World War II. The medical use of heroin highlights the complex relationship between therapeutic benefits and potential for abuse. - Advertisements from the 1940s promoted amphetamines (Benzedrine) for fitness and weight loss. This example illustrates the historical misuse of amphetamines for non-medical purposes. - Cocaine was used as an anesthetic for sore throats and toothaches. - Heroin, a very effective analgesic, was also popular. - Chlorodyne (morphine, chloroform, cannabis, hydrocyanic acid) was used to treat diarrhea and other ailments. This mixture contained multiple psychoactive substances and was highly addictive. - Many deaths occurred due to Chlorodyne addiction. ## Common Illicit Drugs - Methamphetamine, cannabis (THC), and MDMA are frequently encountered. These drugs are commonly abused and contribute to a range of health and social problems. - Detected in 21% of drivers/riders killed in road traffic accidents. Drug-impaired driving is a major cause of traffic fatalities. - GHB is prevalent, particularly in Adelaide. - Cocaine is less common in Adelaide compared to other states. - Opiates are consistently present. - New Psychoactive Substances (NPS) are chemical analogs of older drugs, often based on failed pharmaceuticals. NPS pose significant challenges to detection and regulation due to their constantly evolving chemical structures. ## Emergency Department Drug Intoxication Study in Adelaide - 50% of patients had methamphetamine. This highlights the prevalence of methamphetamine use in emergency department cases. - Alcohol and GHB were the most common drugs detected in patients with central nervous system depressing symptoms. These drugs can cause respiratory depression and coma, posing a serious risk to health. - Diazepam and MDMA were also detected. - Flualprazolam and etizolam were identified as NPS. The detection of NPS in emergency department cases underscores the importance of monitoring emerging drug trends. - The study found that most cases involved multiple drugs (average of 2.9 drugs per person, up to 9 drugs in some cases). Polydrug use is common and can increase the risk of adverse drug interactions and overdose. - 95% of GHB users also had methamphetamine on board. This co-use pattern highlights the complex combinations of drugs that individuals may use. ## Other Illicit Drugs and Testing - Pictures of methamphetamine, MDMA pills, cannabis, and roadside testing devices were shown. - Roadside oral fluid testing has about a 97% accuracy rate. Roadside testing is an important tool for detecting drug-impaired drivers. - Roadside tests are sent to Forensic Science South Australia for definitive testing. Confirmatory testing is essential to ensure the accuracy of drug testing results. ## Opioids and Opiates - Morphine (S8 drug): restricted drug of dependence. - Codeine (S4 drug): prescription-only. - Heroin (S9 drug): illicit. - Oxycodone: another opiate. - Opioids have similar effects to opiates but different chemical structures. Opioids and opiates are potent pain relievers that can also cause respiratory depression and addiction. - Emerging opioid new psychoactive substances: AH-7921, U47700, and Ocfentanil were tested in pharmaceutical trials back in the 80's and 90's.. ## GHB (Gamma-Hydroxybutyrate) - GHB (fantasy) causes euphoria, hypnotic effects, amnesia, drowsiness, and central nervous system depression, including respiratory depression. GHB is a potent central nervous system depressant that can be dangerous, especially when combined with other drugs. - GHB itself is an S9 drug. - Butanediol and gamma-butyrolactone (GBL) are converted into GHB in the body. These precursor chemicals are often used to synthesize GHB illicitly. ## New Psychoactive Substances (NPS) - There are approximately 50 new drugs each year. The rapid emergence of NPS poses significant challenges for drug enforcement and public health. - Since 2010, over 1,500 new drugs have emerged. - These drugs pose detection and harm challenges because their effects often have never been tested on humans.
Forensic Toxicology - Detection, quantification, and interpretation of foreign compounds in forensic samples. - Sample types depend on the case. - Coronial cases: blood, urine, liver, vitreous humor. - Drugs of interest: alcohol, prescription drugs, illicit drugs, pesticides, poisons. - Police samples (suspect or victim): - Urine or blood. - Drugs of interest: alcohol, sedatives, prescription drugs, illicit substances. - Traffic-related: blood must be taken if the driver has an accident and goes to hospital. - Targeted drugs: methamphetamine, THC, and MDMA. ## Drug Detection Methods - Sample preparation is essential to transform and concentrate the sample. Sample preparation steps are crucial for removing interfering substances and concentrating the analytes of interest. - Protein precipitation (e.g., for alcohol). Protein precipitation is used to remove proteins from biological samples, which can interfere with analytical measurements. - Liquid-liquid extraction (adjust pH, add solvent, centrifuge, evaporate). Liquid-liquid extraction is a versatile technique for separating drugs from complex matrices based on their solubility in different solvents. - Solid-phase extraction (SPE) (use a column to capture drugs, wash, and elute). SPE is a selective extraction technique that uses a solid sorbent to capture drugs from a sample, followed by washing and elution steps. - Instrumentation is crucial for analysis. - Liquid chromatography (LC) with mass spectrometry (MS). LC-MS is a powerful analytical technique that combines the separation capabilities of liquid chromatography with the detection capabilities of mass spectrometry. - LC separates compounds. - MS identifies compounds by measuring characteristic fragments. - LC-QTOF provides accurate mass measurements. Quadrupole time-of-flight (QTOF) mass spectrometry provides high-resolution and accurate mass measurements, which are useful for identifying unknown compounds. - Gas chromatography (GC) with mass spectrometry (MS). GC-MS is a widely used analytical technique for separating and identifying volatile compounds. - Ideal for high-concentration samples. - GC separates compounds using a long, thin column. - Mass spectrum is compared to a library for identification. Mass spectral libraries contain reference spectra for a wide range of compounds, allowing for automated identification of unknowns. ## Interpretation of Results - Assess whether a drug concentration is therapeutic, toxic, or lethal. Interpretation of drug concentrations requires consideration of factors such as dose, route of administration, and individual physiology. - Specialists (pharmacologists or forensic pathologists) are best suited for interpretation. These experts have the knowledge and experience to interpret complex toxicological data and provide meaningful conclusions. - Postmortem drug concentrations depend on several factors such as cellular degradation and bacterial activity, which can all affect the postmortem concentrations detected. Postmortem drug concentrations can be affected by factors such as decomposition, redistribution, and metabolism. - Drug interactions and tolerance affect interpretation. Drug interactions can alter the effects of individual drugs, while tolerance can reduce the sensitivity to a drug over time. - Pharmacologists provide opinions on drug effects and interactions. - Analytical toxicologists provide general interpretations, such as identifying a drug as an antipsychotic. ## Conclusion - Overview of illicit drugs and forensic toxicology techniques. - Colleague and I have a podcast called the Tox Pod.