Drug Analysis Amphetamines and Clan Labs

What is the most clandestinely manufactured drug in the US?

Methamphetamine

T/F Amphetamines and related compounds are CNS stimulants. 

True

What is the prototypical compound of the phenylalkylamine series?

• β-phenethylamine

List four pharmacological effects of amphetamines.

• Constriction of smooth muscle of some blood vessels and glands 

• Relaxation of smooth muscle of the gut and bronchi and the blood vessels supplying skeletal muscle 

• Excitation of the heart resulting in increased heart rate and force of contraction 

• Increased rate of glycogenolysis in liver and muscle and release of fatty acids from adipose tissue 

• Excitation of the central nervous system

1. The effects are a result of their _______ activities—that is, their abiliy topotentiate ______ (and ________) neurotransmission in the periphery  and CNS. 

sympathomimetic_, _adrenergic_,_dopaminergic___

List three effects of moderate doses of amphetamines and related compounds.

• wakefulness and alertness

• Elevated mood to the point of elation or euphoria

• Increase initiative and self-confidence

• Increase motor activity

1. Continued use of amphetamines frequently results in _______ and ________. 

_fatigue_,_mental confusion_

T/F Amphetamines have no withdrawal syndrome. 

• False

T/F Amphetamines have been used to reverse the CNS effects of depressants.

True

What causes the anorexic actions of the amphetamines?

• The sympathomimetic effects of amphetamine derivatives in the hypothalamic feeding center results in suppression of appetite

List three methods used to manufacture P‐2‐P.

• Base catalyzed condensation of phenylacetic acid with acetic anhydride 

• Oxidation of 1-aryl propene (APEN) 

• Oxidation of nitrostyrenes (NS).

List three methods used to manufacture methamphetamine or amphetamine from P‐2-P.

• Leuckart Reaction 

• Reductive Amination 

• Aluminum Foil Method 

• Nitrostyrene Reduction

List the two most common methods used to manufacture methamphetamine or amphetamine from ephedrine or pseudoephedrine. 

• HI/Red P (Hydrogenolysis Rxn) 

• Pd-BaSO4 (Hydrogenolysis Rxn) 

• Birch Reduction (Nazi Method)

What type of product is produced when the precursor used is P‐2‐P?

• These reactions produce a racemic product, meaning that there is approximately a 50/50 mixture of each of the l- and d-isomers. This is due to the P-2-P starting material also being racemic.

What type of product is produced when the precursor used is pseudoephedrine or ephedrine? 

These methods produce an enantiomerically pure product (only d- isomer is present) because the starting material contains only the d- isomer.

Is the aluminum foil method endothermic or exothermic? 

• Exothermic

Which isomer of the amphetamine‐related compounds are physiologically active?

d isomer

Why might a meth cook choose to use the Nazi method over the HI/Red P method?

• Historically a popular method of synthesis. However it has become more popular with the modified “one pot” cooks. It requires less space than the other methods.

What are the major components (chemicals) are needed for the HI/ Red P method?

• Red phosphorus 

• Hydriodic acid

What are the major components (chemicals) are needed for the Nazi method?

• Ephedrine/pseudoephedrine 

• Ammonia

• Sodium/lithium

The correct chemical name of the Nazi method is the _______

Birch Method____

Enantiomers:

• non-superimposable mirror image forms of a compound resulting from chirality

Carcinogen

• a cancer causing agent

Chiral

• asymmetric in such a way that the structure and its mirror image are not superimposable

Mutagen

• chemical or physical agent capable of inducing changes in DNA called mutations, often seen in plants used in drug synthesis

Clandestine

kept secret or done secretively, especially because illicit

Teratogen

• an agent or factor which causes malformation of an embryo

Coelute

• the coincident act of two or more chemical compounds eluting from a chromatographic column

Flash point

• the lowest temperature at which vapors above a volatile combustible substance ignite in air when exposed to flame

Toxic:

• very harmful/poisonous 

Melting point:

• the temperature at which a given solid will melt

Boiling point

• The temperature at which a liquid boils and turns to vapor

Allergen

• a substance that causes an allergic reaction

Necrosis:

• the death of most or all of the cells in an organ or tissue due to disease, injury, or failure of the blood supply

Fibrosis

• the thickening and scarring of connective tissue, usually as a result of injury

In amphetamines, which carbon atom is chiral?

• In amphetamine and methamphetamine-type compounds the 2- or α-carbon of the side chain is chiral

In enantiomeric forms:  d stands for ___ ___ and rotates ________

dextrorotatory _;__ polarized light to the right____

In enantiomeric forms:  l stands for ___ ___ and rotates ________

levorotatory; _polarized light to the left____

In enantiomeric forms: R stands for ______ and rotates _______ 

rectus; _1,2,3 priority groups clockwise____ 

In enantiomeric forms: S stands for ______ and rotates __________

sinister_; 1,2,3 priority groups counterclockwise__ 

T/F Enantiomers have opposite optical rotations and have different physical‐chemical  properties. 

• False, they have identical physical-chemical properties

T/F Under normal conditions on a non chiral column, enantiomers cannot be separated on a GC system. 

True

T/F The d‐ and l‐ system of nomenclature describes only the optical activity of enantiomers.

True

R/S configuration describes

priority group rotation

d/l configuration describes

optical rotation

D/L configuration describes

absolute configuration

How can you determine how many stereometric forms are possible for a compound? 

• Compounds possessing more than one chiral center may exist in multiple stereometric forms, the maximum number of which is determined by 2n where n is the number of chiral carbons.

What are two color tests that react with amphetamine‐like compounds?

• Marquis Reagent

• Modified Feigl test 

What is a disadvantage of color tests used with amphetamines?

• The colors can vary or show nonreactive if amphetamine is cut with another nonamphetamine drug

What are the most informative IR bands for amphetamine‐like compounds?

• The most informative bands for amphetamine- type compounds are the two relative strong absorptions in the Fingerprint region (750 to 690 cm-1)

Those bands represent what molecular interactions?

• Representative of C-H bending vibrations of a monosubstituted aromatic ring.

T/F IR is the best technique for distinguishing racemic and pure enantiomers.

False

What is one limitation associated with IR analysis of amphetamines?

The differences in the spectra of d-(+)-S-amphetamine HCl or l-(-)-R-amphetamine HCl and racemic amphetamine HCl are very subtle, suggesting that it is very difficult to distinguish racemate and pure enantiomers of amphetamine.

What is one limitation of GC/MS analysis of amphetamines?

All isomers have the same molecular weight and similarities in their mass spectra

List two derivatizing agents that can be used in GC/MS analysis. 

• acetic anhydride

• trifluoroacetic anhydride (TFAA or TFA)

Why should methanol not be used as a GC solvent when analyzing amphetamines? 

• The combination of the heat and methanol in the injection port can create compounds that are not actually present in the sample

What are the two recommended solvents for GC analysis of the amphetamines?

• CHCl3 

• Hexane

List the schedules of meth, amphetamine, and N,N‐dimethylamphetamine. 

• Meth: schedule 2

• Amphetamine: schedule 2

• N,N‐dimethylamphetamine: schedule 1

What is one drawback of TPC? 

• The retention times are close together when TPC is used

What caustic gas, which is colorless and odorless, can be produced when manufacturing  methamphetamine? 

• Phosphine gas

List 3 physical hazards associated with clan labs.

• Fire hazards

• Inhalation hazards

• Skin irritants 

What precursor is used to manufacture PCP? 

• Piperidine

What does PCP stand for? 

• phencyclidine

T/F Hydrogenolysis reactions displace the benzylic hydroxyl group of the chiral starting material.

False

Why might a meth cook choose to use the Nazi method over the HI/Red P method?

precursors are more readily available 
-simpler and safer method
-lower profile (draws less attention)
-better yield and purity