Chapter 7 & 8 Drugs and Toxicology “Having sniffed the dead man’s lips, I detected a slightly sour smell, and I came to the conclusion that he had poison forced upon him.” —Sherlock Holmes, in Sir Arthur Conan Doyle’s A Study in Scarlet

Kendall/Hunt Publishing Company Define Drug Controlled Substance Illicit Drug Prescription Drug Over the Counter Drug Poison Kendall/Hunt Publishing Company

Kendall/Hunt Publishing Company Drug A natural or synthetic substance designed to affect humans or animals psychologically or physiologically. Kendall/Hunt Publishing Company

Kendall/Hunt Publishing Company Controlled substance Identified under the Federal Schedules of the Controlled Substances Act Kendall/Hunt Publishing Company

Kendall/Hunt Publishing Company Illicit Drug An illegal substance used for pleasure but not necessarily defined in the Federal Controlled Substance Act Kendall/Hunt Publishing Company

Kendall/Hunt Publishing Company Prescription Drug A doctor must prescribe a drug for a specific reason. Misuse makes it an illicit drug. Kendall/Hunt Publishing Company

Kendall/Hunt Publishing Company Over the Counter (OTC) No restrictions on purchase Misuse of these can and does occur Pseudoephedrine misuse leads to curtailed access Kendall/Hunt Publishing Company

Kendall/Hunt Publishing Company Poison Almost anything can be a poison if used inappropriately Poison Control Center frequent calls Children’s Tylenol Children’s Vitamins with iron Kendall/Hunt Publishing Company

Chapter 7 & 8 Drugs and Toxicology “All substances are poisons. There is none which is not. The right dose differentiates a poison and remedy.” —Paracelsus (1495-1541). Swiss physician and chemist

Kendall/Hunt Publishing Company Drugs Students will learn: How to apply deductive reasoning to a series of analytical data. The limitations of presumptive (screening) tests. The relationship between the electromagnetic spectrum and spectroscopic analysis. The dangers of using prescription drugs, controlled substances, over-the-counter medications, and illegal drugs. Kendall/Hunt Publishing Company

Kendall/Hunt Publishing Company Drugs Students will be able to: Chemically identify illicit drug types. Classify the types of illicit drugs and their negative effects. Discuss the federal penalties for possession and use of controlled substances. Explain the need for confirmatory tests. Kendall/Hunt Publishing Company

Kendall/Hunt Publishing Company Drugs Describe IR, UV-VIS spectroscopy, and GC-MS Present and interpret data with graphs. Use the Physicians’ Desk Reference (PDR) to identify pills. Use technology and mathematics to improve investigations and communications. Kendall/Hunt Publishing Company

Kendall/Hunt Publishing Company Drugs and Crime A drug is a natural or synthetic substance designed to affect the subject psychologically or physiologically. “Controlled substances” are drugs that are restricted by law Controlled Substances Act is a law that was enacted in 1970; it lists illegal drugs, their category and their penalty for possession, sale or use. Kendall/Hunt Publishing Company

Controlled Substances Act Schedule I—high potential for abuse; no currently acceptable medical use in the US; a lack of accepted safety for use under medical supervision Schedule II—high potential for abuse; a currently accepted medical use with severe restrictions; abuse may lead to severe psychological or physical dependence Schedule III—lower potential for abuse than the drugs in I or II; a currently accepted medical use in the US; abuse may lead to moderate physical dependence or high psychological dependence Schedule IV—low potential for abuse relative to drugs in III; a currently accepted medical use in the US; abuse may lead to limited physical or psychological dependence relative to drugs in III Schedule V—low potential for abuse relative to drugs in IV; currently accepted medical use in the US; abuse may lead to limited physical or psychological dependence relative to drugs in IV Kendall/Hunt Publishing Company

Examples of Controlled Substances and Their Schedule Placement Schedule I—heroin (diacetylmorphine), LSD, marijuana, ecstasy (MDMA) Schedule II—cocaine, morphine, amphetamines (including methamphetamines), PCP, Ritalin Schedule III—intermediate acting barbiturates, anabolic steroids, ketamine Schedule IV—other stimulants and depressants including Valium, Xanan, Librium, phenobarbital, Darvon Schedule V—codeine found in low doses in cough medicines Kendall/Hunt Publishing Company

Identification of Drugs PDR—Physicians’ Desk Reference Field Tests—presumptive tests Laboratory Tests—conclusive tests Kendall/Hunt Publishing Company

Physicians’ Desk Reference PDR—a physicians’ desk reference is used to identify manufactured pills, tablets and capsules. It is updated each year. This can sometimes be a quick and easy identifier of the legally made drugs that may be found at a scene. The reference book gives a picture of the drug, whether it is a prescription, over the counter, or a controlled substance; as well as more detailed information about the drug. Kendall/Hunt Publishing Company

1. Scan your product insert Product Inserts: use the guide to help you interpret your example. Answer these questions on notebook paper. 1. Scan your product insert A. List the generic name and indications B. List contraindications (and describe what that means) C. List warnings and adverse reactions D. Describe dosage 2. Describe “black box warnings” and give 7 examples…check the handout for these. Does your product have a black box warning?

Kendall/Hunt Publishing Company Drug Identification Screening or presumptive tests Spot or color tests Microcrystalline test— a reagent is added that produces a crystalline precipitate which is unique for a certain drug. Chromatography Confirmatory tests Spectrophotometry Ultraviolet (UV) Visible Infrared (IR) Mass spectrometry Kendall/Hunt Publishing Company

Presumptive Color Tests Marquis—turns purple in the presence of most opium derivatives and orange-brown with amphetamines Dillie-Koppanyi—turns violet-blue in the presence of barbiturates Duquenois-Levine—turns a purple color in the presence of marijuana Van Urk—turns a blue-purple in the presence of LSD Scott test—color test for cocaine, blue Kendall/Hunt Publishing Company

Kendall/Hunt Publishing Company Chromatography A technique for separating mixtures into their components Includes two phases—a mobile one that flows past a stationary one. The mixture interacts with the stationary phase and separates. Kendall/Hunt Publishing Company

Types of Chromatography Paper Thin Layer (TLC) Gas (GC) Pyrolysis Gas (PGC) Liquid (LC) High Pressure Liquid (HPLC) Column Kendall/Hunt Publishing Company

Kendall/Hunt Publishing Company Paper Chromatography Stationary phase—paper Mobile phase—a liquid solvent Capillary action moves the mobile phase through the stationary phase Kendall/Hunt Publishing Company

Thin Layer Chromatography Stationary phase— a thin layer of coating (usually alumina or silica) on a sheet of plastic or glass Mobile phase— a liquid solvent Kendall/Hunt Publishing Company

Kendall/Hunt Publishing Company Retention Factor (Rf) This is a number that represents how far a compound travels in a particular solvent It is determined by measuring the distance the compound traveled and dividing it by the distance the solvent traveled. If the Rf value for an unknown compound is close to or the same as that for the known compound, the two compounds are likely similar or identical (a match). Kendall/Hunt Publishing Company

Kendall/Hunt Publishing Company Gas Chromatography Phases Stationary—a solid or a viscous liquid that lines a tube or column Mobile—an inert gas like nitrogen or helium Analysis Shows a peak that is proportional to the quantity of the substance present Uses retention time instead of Rf for the qualitative analysis Kendall/Hunt Publishing Company

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Uses of Gas Chromatography Not considered a confirmation of a controlled substance Used as a separation tool for mass spectroscopy (MS) and infrared spectroscopy (IR) Used to quantitatively measure the concentration of a sample. (In a courtroom, there is no real requirement to know the concentration of a substance. It does not affect guilt or innocence). Kendall/Hunt Publishing Company

Kendall/Hunt Publishing Company Mass Spectrometry Gas chromatography has one major drawback, it does not give a specific identification. Mass spectrometry cannot separate mixtures. By combining the two (GCMS), constituents of mixtures can be specifically identified. Kendall/Hunt Publishing Company

Kendall/Hunt Publishing Company Mass Spectrometer A machine used to weigh molecules A molecular scale Kendall/Hunt Publishing Company

Kendall/Hunt Publishing Company How is MS used? A mass spectrometer helps scientists ID molecules Determine how many molecules are present Determine what atoms are in a molecule Determine how the atoms are arranged Kendall/Hunt Publishing Company

Kendall/Hunt Publishing Company Pocket change sorted Kendall/Hunt Publishing Company

Kendall/Hunt Publishing Company Sorting and Counting POCKET CHANGE MIXTURE OF MOLECULE AND FRAGMENTS Penny, nickel, dime, quarter, half dollar, dollar Sort change by value or size Stack them up to sort them visually Mixture of different molecule fragments Sort fragments by mass Show amount of each fragment on bar graph Kendall/Hunt Publishing Company

Molecular fragments sorted Kendall/Hunt Publishing Company

Kendall/Hunt Publishing Company HOW? Using ions An ion is an electrically charged atom or molecule Molecules must be charged to be measured by a mass spec A mass spec “weighs” molecules by electrically attracting and repelling ions with carefully controlled charges and force fields. Kendall/Hunt Publishing Company

Kendall/Hunt Publishing Company Let’s get charged up! First, the mass spec ionizes (or charges) the molecules It also breaks apart the big molecule into pieces…like tearing apart a jigsaw puzzle This is called ionization Kendall/Hunt Publishing Company

Kendall/Hunt Publishing Company Sort it out! It sorts all of these charged particles out by size Kendall/Hunt Publishing Company

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Kendall/Hunt Publishing Company Like a pinball machine…a certain amount of force sends the ball where you want it A different size ball requires different force Kendall/Hunt Publishing Company

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What do the patterns tell us? MOLECULAR FINGERPRINTS Scientists recognize the pieces and assemble them to identify the compound. Each compound produces a unique spectrum. MS Fragments...pieces of a puzzle

Kendall/Hunt Publishing Company Mass Spectra Each molecular species has its own unique mass spectrum. Kendall/Hunt Publishing Company

Kendall/Hunt Publishing Company Spectroscopy Spectroscopy—the interaction of electromagnetic radiation with matter. Spectrophotometer—an instrument used to measure and record the absorption spectrum of a chemical substance. Kendall/Hunt Publishing Company

Kendall/Hunt Publishing Company Spectrophotometry Components A radiation source A frequency selector A sample holder A detector to convert electromagnetic radiation into an electrical signal A recorder to produce a record of the signal Types Ultraviolet Visible Infrared Kendall/Hunt Publishing Company

Kendall/Hunt Publishing Company Infrared Spectometry Material absorbs energy in the near-IR region of the electromagnetic spectrum. Compares the IR light beam before and after passing through a transparent sample. Result—an absorption or transmittance spectrum Gives a unique view of the substance; like a fingerprint Kendall/Hunt Publishing Company

IR Spectrophotometry and Mass Spectrometry Both work well in identifying pure substances. Mixtures are difficult to identify in both techniques Both are compared to a catalog of knowns Kendall/Hunt Publishing Company

Human Components Used for Drug Analysis Blood Urine Hair Gastric Contents Bile Liver tissue Brain tissue Kidney tissue Spleen tissue Vitreous Humor of the Eye Kendall/Hunt Publishing Company

Kendall/Hunt Publishing Company Challenges of Tox Drugs must be isolated from body components, such as urine, blood, brain vitreous humor, stomach contents, liver, bile, brain Kendall/Hunt Publishing Company

Kendall/Hunt Publishing Company Challenges of Tox Drugs in the body are changed chemically as the body metabolizes the drug. Scientists must understand the process and look for the metabolites. Kendall/Hunt Publishing Company

Kendall/Hunt Publishing Company Challenges of Tox If the patient is alive, testing must be fast to provide medical care. The quantity of drug present is often important. Remember, the difference between medicine and poison is often the dose. Kendall/Hunt Publishing Company

Kendall/Hunt Publishing Company Challenges of Tox The time involved is important. For example, in DUI cases, the body is breaking down alcohol at a predictable rate…people “sober up” If the blood sample is taken hours after an accident, scientists will try to calculate what the level was at the time of the accident. Kendall/Hunt Publishing Company

Kendall/Hunt Publishing Company ID MJ Easy, right? It’s a plant It’s easy to ID, but difficult for a chemist to defend in court because chemists are not botanists! Kendall/Hunt Publishing Company

Kendall/Hunt Publishing Company The DUCK TEST Does it look like MJ? Does it smell like MJ? Pretty good chance it is MJ. The Duck Test won’t fly in court! We need science to prove it! Kendall/Hunt Publishing Company

Kendall/Hunt Publishing Company QUICK TESTS Look for cystolithic hairs Do a chemical test for cystolithic hairs Add HCl HCl reacts with CaCO3 in hairs to form bubbles Kendall/Hunt Publishing Company

Kendall/Hunt Publishing Company GOOD First another presumptive test: Quick, easy, and sensitive NOT specific Add Duquenois-Levine chemical MJ will turn purplish in color The problem is, so will other things Kendall/Hunt Publishing Company

BETTER Chromatography, a confirmatory test, but still only screening Components of MJ are separated using chromatography We see them using D-L, but this test offers more info due to separation Dip strip of paper in D-L solution Allow colored components to separate

Kendall/Hunt Publishing Company BEST: prove it with MS Kendall/Hunt Publishing Company

People of Historical Significance Arthur Jeffrey Dempster was born in Canada, but studied and received his PhD from the University of Chicago. He began teaching physics there in 1916. In 1918, Dempster developed the first modern mass spectrometer. His version was over 100 times more accurate than previous ones developed, and established the basic theory and design of mass spectrometers that is still used to this day. Kendall/Hunt Publishing Company

People of Historical Significance Francis William Aston was a British physicist who won the 1922 Nobel Prize in Chemistry for his work in the invention of the mass spectrograph. He used a method of electromagnetic focusing to separate substances. This enabled him to identify no fewer than 212 of the 287 naturally occurring elemental isotopes. Kendall/Hunt Publishing Company