Drug Chemistry Training (General Drugs Section)

1. List the following opioids in order of potency from lowest to highest:

1. potency from lowest to highest: · Hydrocodone: 3 · Codeine: 4 · Hydromorphone: 1 Oxycodone

1. Describe in simple terms that a jury could understand how synthetic cathinones are controlled in Kentucky.

Controlled by class/structure, not by name.

What compound is typically used to check the performance of a UV-Vis instrument?

Holmium oxide.

What is the purpose of the laser in an FTIR?

Laser used to align the movable mirror.

1. Why must one be extremely careful when analyzing fentanyl exhibits?

Transdermal systems can cause exposure.

Give the name for cocaine based on it being a substituted ecgonine compound.

benzoylmethylecgonine.

What does "ANOR" stand for in the ANOR extraction technique?

· "Alternate Non-Aqueous Organic Ratio".

Describe the typical method by which many home cooks convert cocaine HCl to "crack" cocaine.

· "Crack" cocaine produced by dissolving cocaine HCl in water, adding a base to the mixture, and heating the mixture to evaporate HCl, leaving behind crystals.

In a literature reference, a strong IR peak is listed at 10 µm (micrometers). What is the frequency in cm-1?

· 1000 cm-1 (10 µm = 0.001 cm; 1/0.001)

What is the molecular weight of cocaine?

· 303.4 g/mol.

Define the term alkaloid.

· A group of basic, nitrogenous plant products that have a marked physiological action. The majority of these compounds are complex, heterocyclic compounds.

According to the Drug Chemistry Analytical Manuals, what are the data interpretation criteria for a positive log search match? Please cite the reference where this information is found.

· A logo search shall be considered positive if the returned result matches a tablet/capsule/preparation in, at a minimum, color, physical description, and markings.

List whether liquid chromatography or ion chromatography could be used to analyze the following:

· A mixture of steroids: liquid chromatography. · A mixture of codeine HCl, codeine PO4, and codeine SO4: ion-chromatography. · Residue left at a clan lab producing methamphetamine by the red phosphorus, hydroiodic acid, and ephedrine method: liquid chromatography.

Describe one extraction method to separate hydrocodone from a hydrocodone/acetaminophen preparation.

· ANOR extraction; NH4 OH (ammonium hydroxide) saturated hexane as reagent. · Reagent preparation: combine one (1) part 30% aqueous NH4 OH to ten (10) parts hexane. Shake to mix and allow layers to separate. The layer to be used for extraction is the top layer. · Procedure: place the sample to be extracted into a vial. Add several milliliters of solvent and allow the sample to soak. Decant the extract with a pipette or filter extract through filter paper. Concentrate the extract over steam bath or under air if necessary.

1. Are barbiturates acidic, neutral, or basic compounds?

· Acidic

What are some advantages of CE over GC? Disadvantages?

· Advantages: 1. Amendable to the analysis of ionic and neutral solutes. 2. Higher efficiency. 3. Rapid method development and optimization. 4. Cheaper capillary. · Disadvantages: 1. Limited sensitivity. 2. Difficult fraction collection.

What are some advantages of HPLC over GC? What are some disadvantages?

· Advantages: 1. Capable of analyzing a much wider range of components. 2. Compounds that are thermally liable, exhibit high polarity, or have high molecular mass may all be analyzed using HPLC. 3. Isomers can be separated and identified without derivatization. · Disadvantages: 1. Lower number of theoretical plates for a moderate resolution rather than high. 2. Mobile phase may have a delirious long-term effect on the stationary phase. 3. Generates a lot of waste.

What does ATR stand for?

· Attenuated Total Reflectance.

1. Barbiturates are derivatives of what compounds?

· Barbituric acid, a synthetic condensation product of malonic acid and urea.

Quantitative analysis by UV is made possible by what law or principle?

· Beer-Lambert Law: A = log10(Io/I) = sbc · A = the measured absorbance · s = absorbance coefficient (formerly called the extinction coefficient) · c = the concentration of the absorbing species · b = the cell path length (usually 1 cm)

1. What barbiturate is found in the pharmaceutical preparation of Fioricet?

· Butalbital.

Define chromophore and auxochrome.

· Chromophore: the unsaturated groups responsible for the electronic absorption seen in the near ultraviolet region (typically, carbonyl, nitro groups [R-bands], conjugated dienes [K-bands], aromatic rings [B-bands, E-bands]). · Auxochrome: chemical groups that do not produce much UV absorption by themselves but that influence the intensity and wavelengths of an adjacent chromophore. Usually have lone pairs of electrons (-OH, -NH2, and halogens).

Name a reference book that is likely to contain information about solubilities.

· Clarke's Handbook, or the Merck Index.

Describe in simple terms the difference between cocaine HCl and cocaine base.

· Cocaine HCl, or the powdered form of cocaine, is extracted from the coca plant, and can be administered intranasally (snorted), or dissolved in water and injected. Cocaine base is produced by dissolving cocaine HCl in water, adding a base like ammonia, and then adding a solvent, typically ether. The cocaine base is extracted by evaporation. Crack, another form of cocaine base, is produced by dissolving cocaine HCl in water, mixing with a base, and heating this mixture to remove hydrochloride. Cocaine base can be smoked.

Why is cocaine commonly classified as a "narcotic" when it differs in pharmacological action from nearly all other compounds similarly classified?

· Cocaine can be used as a local anesthetic, but is also a controlled substance.

A mixture of cocaine and inositol will produce an IR spectrum that matches:

· Cocaine: · Inositol: · Neither: NEITHER is correct answer. It will be a mixture of the two.

What are some common controlled substances that might be particularly amenable to analysis by UV-Vis spectrophotometry?

· Codeine, cocaine, amphetamine, fentanyl, oxycodone, hydrocodone, ketamine

According to the Drug Chemistry Analytical Manuals, what is needed in addition to a logo search to report a particular item as "Identical in appearance to a pharmaceutical preparation of _______, Schedule # [narcotic or non-narcotic]."?

· Color, physical description, and markings. Photograph. DC-AM Case Approach 4.3.

What chemical structure is essential for the absorption of ultraviolet light?

· Conjugated double bonds.

What is one method that could be employed to differentiate enantiomers via gas chromatography?

· Derivatization of enantiomers via chiral or achiral reagents prior to analysis.

What is the typical source for ultraviolet radiation in an ultraviolet spectrophotometer?

· Deuterium lamp.

1. What is the chemical name for heroin? What Schedule is it in Kentucky?

· Diacetylmorphine. Schedule I.

1. Many controlled stimulants were formerly prescribed for what purpose?

· Diet pills, or antisleep medication.

What is an emulsion? How can they be prevented and what can be done when one occurs?

· Emulsion occurs when a sample will have mutual solubility in the aqueous and organic solvents. The immediate solubility in each of the two phases makes it difficult to quantitatively collect from one phase or another. · The simplest way to prevent emulsion from occurring is to gently swirl instead of shake the seporatory funnel. · If emulsion has occurred, addition of a small amount of a different solvent will adjust the solvent properties of the separation, which will break the emulsion.

Determine whether the following statements are true or false:

· Enantiomeric determination of a compound is never important in the controlled substances section: · Compounds can have, at most, one chiral center: · All enantiomers are isomers, but not all isomers are enantiomers:

Name the two distinct species of coca to which all cultivated coca plants belong.

· Erythroxylum coca Lam. (or E. coca) - the most important species from which almost all commercial cocaine is derived. · Erythroxylum novogranatense var. novogranatense Hieronymus - commonly known as Colombian coca.

Which instrument available in your laboratory is capable of providing distinguishing information between cocaine HCl and cocaine base?

· FTIR

1. What analytical technique would best differentiate 2-fluoromethcathinone from 3-fluoromethcathinone? Does this differentiation matter?

· FTIR, this differentiation does not matter.

1. True or false: Synthetic cathinones are commonly called "bath salts" because the original drug was extracted from a commercially available bath product.

· False

True or False: State (Kentucky) regulations/penalties differ between offenses involving cocaine HCl and cocaine base.

· False.

True or false. Solution pH has no effect on UV-Vis spectrum.

· False. For example, phenolic -OH groups exhibits a shift to a longer wavelength accompanied by an increase in absorbance intensity when the pH of the solvent is changed from neutral to alkaline.

1. Name the principle ingredient in the following pharmaceutical preparations and list its schedule in Kentucky.

· Fastin: phentermine (III) · Adderall: amphetamine (II) · Ritalin: methylphenidate (IV) · Cylert: permoline (IV) · Desoxyn: methamphetamine (II) · Vyvanse: lisdexamfetamine (II)

1. What is the official taxonomic genus and species of the opium poppy?

· Genus: Papaver · Species: Papaver somniferum L.

What is a typical source of infrared radiation for an FTIR instrument?

· Globar (thermal light source)

What does HPLC stand for? What does CE stand for?

· HPLC: High-Performance Liquid Chromatography · CE: Capillary Electrophoresis

1. What are several common slang terms used for methamphetamine?

· Ice, crystal, glass

Describe a Soxhlet extraction. When might this be useful?

· In conventional Soxhlet, the sample is placed in a thimble-holder and during operation is gradually filled with condensed fresh solvent from a distillation flask. When the liquid reaches an overflow level, a siphon aspirates the whole contents of the thimble-holder and unloads it back into the distillation flask, carrying the extracted analytes in the bulk liquid. This operation is repeated until complete extraction is achieved. · Soxhlet extraction is only required where the desired compound has a limited solubility in a solvent, and the impurity is insoluble in that solvent. If the desired compound has a high solubility in a solvent then a simple filtration can be used to separate the compound from the insoluble substance. · The extraction was originally designed for extracting lipids from solid materials, but it can also be useful for extracting THC from plant material.

Why is the base form of cocaine smokeable, while the HCl form is not?

· In its base form, cocaine can be smoked because it melts at a much lower temperature (~80 °C) than cocaine HCl (~180 °C).

Define the following terms: Isomer: Diastereomer: Enantiomer: Geometric isomer: Chiral: Dextrorotatory/levorotatory: R (rectus)/S (sinister):

· Isomer: one of several chemical species or molecular entities that have the same molecular formula but different constitutional formula and potentially different physical and/or chemical properties. · Diastereomer: stereoisomers that are not related as mirror images; characterized by differences in physical properties, and by some differences in chemical behavior towards achiral as well as chiral reagents. · Enantiomer: mirror-image isomers, non-super imposable. · Geometric isomer: cis-trans isomerism, show the relationship between two ligands attached to separate atoms that are connected by a double bond or are contained in a ring, cis = same side of plane, trans = opposite side of plane. · Chiral: having chirality, meaning that the geometric properties of a molecule has no symmetry elements of the second kind (a mirror plane, a center of inversion, or a rotation reflexion axis). · Dextrorotatory/levorotatory: polarimeter used to measure the direction of rotation of enantiomers. · R (rectus)/S (sinister): denotes the direction of rotation of a chiral center.

1. If a solution containing methamphetamine was to be concentrated by evaporating off some of the solvent, why might one add a couple drops of HCl to the solution first.

· Keep the meth from evaporating off and to keep the solution basic.

What is the most accurate source for determining the schedule of a particular controlled substance?

· Kentucky Revised Statutes Chapter 218A.

1. Under what schedule are which barbiturates found in Kentucky law?

· Long Acting: Schedule III (Schedule IV federally) · Intermediate: Schedule II & III · Short: Schedule II · Ultrashort: Schedule III

1. How are barbiturates categorized? What are the categories? List one example from each category.

· Long-acting: Barbital · Intermediate-acting: Amobarbital · Short-acting: Cyclobarbital · Ultrashort-acting: Sodium Hexobarbital

1. What are some common medical uses for barbiturates?

· Long-acting: day-time sedatives to control epileptic seizures. · Intermediate-acting: longer-lasting sedatives. · Short-acting: used to induce sleep. · Ultrashort: mostly used as an anesthetic.

1. Name the active opioid ingredient in the following pharmaceutical preparations and its schedule in Kentucky:

· Lortab: Hydrocodone (III) · Percocet: Oxycodone (II) · Dilaudid: Hydromorphone (II) · Tylenol 3: Codeine (III) · Oxycontin: Oxycodone (II) · Vicodin: Hydrocodone (III)

1. What is at least one color test that is useful for a wide range of opiate drugs? Choose 3 opiate examples and indicate the expected result for the color test(s) you named.

· Marquis: violet - heroin, morphine, codeine. · Mecke: green/blue - heroin, morphine, codeine

1. What names does the active ingredient in Demerol go by? By which of these names is it controlled in Kentucky?

· Meperidine (II), Pethidine (scheduled as "meperidine")

For both cocaine HCl and cocaine base, indicate whether the compound is soluble in the following solvents:

· Methanol: HCl - soluble, Base - soluble · Chloroform: HCl - soluble, Base - soluble · Ethyl ether: HCl - insoluble, Base - soluble · Hexanes: HCl - insoluble, Base sparingly soluble

In what type of medical procedures might cocaine be used?

· Minor surgeries (topical anesthesia), aerosol to numb nasal passages, numb eye or throat in surgery, and used to deaden the pain of chronic sores.

1. Pharmacologically, how are benzodiazepines classified?

· Minor tranquilizers; Depressants

1. Draw the structures of morphine, heroin, oxycodone, and hydrocodone.

· Morphine: · Heroin: · Oxycodone: · Hydrocodone:

1. Why do barbiturates lend themselves to analysis by UV particularly well?

· Most barbiturates exhibit extremely high molar absorptivities in the ultraviolet region of the spectrum (340-220 nm).

How much would the signal to noise ratio improve on a sample scanned 16 times as opposed to the same sample scanned 1 time?

· Multiple scans can improve sensitivity and reduce noise. Averaging 16 measurements can improve the signal to noise ratio 4 times.

1. What molecular structure gives rise to the 44 m/z ion in the mass spectrum of amphetamine?

· N-ethyl amine

1. What molecular structure gives rise to the 58 m/z ion in the mass spectrum of amphetamine?

· N-methyl ethyl amine

1. Would it be surprising to find a morphine peak in the GCMS of a heroin sample? Why or why not?

· No, morphine base is the immediate precursor of heroin, and is a breakdown product.

How many moving parts does an FTIR have and what are they?

· One: a moveable mirror.

What is the difference between an opiate and an opioid? Provide an example of each.

· Opiates, or opium derivatives, are made directly from a naturally occurring opium alkaloid and is referred to as semi-synthetic (ex. Morphine). · Opioids are compounds that are not produced from naturally occurring opium alkaloids, but have similar narcotic-analgesic pharmacological effects (ex. Methadone).

What are the criteria for making an identification of a controlled substance by IR as described by the Drug Chemistry Analytical Manual? What is the requirement for a positive comparison of a spectrum from the same manual? Where, specifically, in the manual is this information found?

· Option 1: comparing a full-scale IR spectrum of the casework sample to a full-scale IR spectrum of a reference material run on the same instrument using the same instrument conditions. · Option 2: comparing a full-scale IR spectrum of the casework sample to a full-scale IR spectrum of a reference material published in two (2) accepted literature references (print or electronic). · A positive comparison is made when the casework sample spectrum compares favorably to the reference material or literature/electronic reference spectrum in both its overall appearance and in the presence of the major IR bands to that compound.

1. Draw the structure of the following:

· Phenethylamine: · Methamphetamine: · Amphetamine: · Pseudoephedrine:

According to the Drug Chemistry Analytical Manuals, what are the accepted log search references? Where, specifically, are these located in the manual?

· Physician's Desk Reference · Identidex · Identadrug · Drug ID Bible · DEA Tablet Logo Index · The specific manufacturer's website or packaging insert · Pillbox (sponsored by the National Library of Medicine) · Dailymed (sponsored by the National Library of Medicine) · Drugs.com (references from IBM Micromedex, Cerner Multum, Wolters Kluwer, National Library of Medicine. · These references are located in KSP DC-AM 18 Pharmaceutical Logo Searches, Section 1.1, pg. 4.

1. What dosage form is fentanyl most commonly found in?

· Pill, liquid, or patch.

In non-technical terms, explain what an interferometer does.

· Plotted data showing the distance of a mirror against the intensity of a wavelength of light. Since the mirror in an FTIR moves at a controlled speed, the data can be shown in terms of time.

What compound is most commonly used to validate the performance of an IR instrument?

· Polystyrene.

1. What is the primary medical use of opioids?

· Primary medical use of opioids is to treat/relieve pain.

1. What are the active ingredients in Darvon N tablets? How is it scheduled in Kentucky?

· Propoxyphene (IV).

To which Schedule does cocaine belong, in Kentucky?

· Schedule II.

1. What schedule in Kentucky is buprenorphine? What is it commonly used for, medically?

· Schedule III, low doses is used an as analgesic, high doses is used to block opioid receptors.

1. Under what schedule are benzodiazepines classified in Kentucky?

· Schedule IV.

1. What are at least 2 secondary medical uses of opioids?

· Secondary medical uses of opioids are: 1. Alleviate diarrhea. 2. Induce anesthesia.

Describe the following terms: Solubility: Dry Extraction: Liquid-liquid extraction:

· Solubility: the capacity of two or more substances to form, without chemical reaction, a homogeneous molecular (or colloidal) dispersion; the solubility of a solid in a liquid refers to that concentration that is reached when a fixed amount of liquid has dissolved as much of the solid as it can hold at equilibrium (at a specific temperature). · Dry Extraction: a dry extraction procedure is part of the qualitative scheme and involves mixing a portion of an unknown powder with a specific solvent, filtration, collection of the extract, and evaporation of the extract to dryness. · Liquid-liquid extraction: a drug dissolved in one solvent (usually the aqueous phase) may be separated from accompanying impurities by shaking out with a second immiscible solvent (the organic phase) in which the substance sought is quite soluble, but the impurities are not.

To which pharmacological category does cocaine belong? (Depressant, stimulant, hallucinogen, etc.).

· Stimulant.

What does the term "salting out" mean?

· The addition of brine or salt water, which increases the ionic strength of the aqueous layer and facilitates separation of the two solvent phases.

What is the difference between an IR spectrum and an interferogram?

· The interferogram is the interference signal measured by the detector as a function of the optical path length difference. The IR spectrum is computed from the interferogra by performing a Fourier transform that shows the signal as absorbance at various frequencies.

1. What is the source of the vinegar-like odor that frequently emanates from black tar heroin?

· The odor comes from the crude processing methods used to illicitly manufacture heroin. A byproduct of the reaction used to make heroin from morphine is acetic acid that typically has a vinegar-like odor.

How is the concept of pKa useful when devising or performing an acid/base extraction?

· The pKa is closely related to the pH of a solution; a low pKa value will also mean a low pH value. This can come in handy when adjusting the pH of a solution for extraction. Also tells you the pH at which half the species is ionized.

What criteria should be considered when choosing a solvent to dissolve a sample in prior to obtaining an ultraviolet spectrum of the solution?

· The sample should be sufficiently soluble in the selected solvent. · The solvent must be transparent over the wavelength range of interest.

1. What are the three main alkaloids of the opium poppy from which most opiates are derived?

· Three (3) main alkaloids of the opium poppy: 1. Thebaine 2. Codeine 3. Morphine

True or False: Federal regulations/penalties differ between offenses involving cocaine HCl and cocaine base.

· True.

What useful information might UV-Vis provide in drug analysis?

· UV-Vis can identify and quantitate a drug substance; most organic compounds exhibit useful spectra in the ultraviolet region. · The absorbance of a substance is directly correlated to its concentration, so it is possible to calculate the amount of an unknown substance in a solution.

Name two common detectors for an HPLC instrument.

· Ultra-violet (UV), and mass spectrometric (MS).

In simple terms that a jury could understand, explain infrared spectroscopy.

· Using infrared radiation in the 4000 - 400 cm-1 frequency, molecules will absorb this IR radiation, depending on the type of bond between specific elements within the molecule. An IR source will promote IR radiation at different wavelengths in the form of light which will pass through the sample being examined. The light will then pass into the detector, which will communicate with an electronic output to show the data in the form of a spectrum. Using the data from that spectrum, it is possible to determine the identity of the substance in question based on where and how intense the IR radiation was absorbed.

Using any accepted pharmaceutical identifier reference, list the active ingredient in the following tablets based on their logo imprints (please also cite the pharmaceutical identifier reference used):

· WATSON 540: Acetaminophen/Hydrocodone Bitartrate · OC 80: OxyContin · 93 833: Clonazepam · GG249: Alprazolam · V 3605: Acetaminophen/Hydrocodone Bitartrate · Pharmaceutical identifier reference used: Drugs.com

List all combinations of diastereomers and enantiomers for cocaine (hint: there should be a total of 8).

· d-Cocaine · l-Cocaine · d-Pseudococaine · l-Pseudococaine · d-Allococaine · l-Allococaine · d-Pseudoallococaine · l-Pseudoallococaine

Can FTIR differentiate the following?

· d-cocaine from l-cocaine: no · methamphetamine from phentermine: yes · cocaine HCl from cocaine base: yes

What does the term pH mean? What about pKa?

· pH: the negative logarithm of the effective hydrogen-ion concentration in gram/liter of the solution; a measure of acidity and alkalinity of a solution. · pKa: the negative logarithm of the acid dissociation constant, or Ka value. It is one method used to determine the strength of an acid; a lower pKa value indicates a stronger acid. That is, the lower value indicates the acid more fully dissociates in water.

What are the x and y axes of the interferogram taken by an FTIR?

· x axes = frequency (cm-1), y axes = absorbance.