MChem Master of Chemistry Master of Chemistry: Pharmaceutical Chemistry 2 — Questions and Answers
Question 1: Which pharmacokinetic parameter describes the fraction of an administered dose that reaches systemic circulation unchanged?
- Clearance
- Bioavailability (Correct answer)
- Volume of distribution
- Half-life
Correct answer: Bioavailability
Bioavailability (F) quantifies the fraction of dose reaching systemic circulation in unchanged form, accounting for absorption and first-pass metabolism.
Question 2: In prodrug design, which bond type is most commonly used to mask a carboxylic acid to improve membrane permeability?
- Amide bond
- Ester bond (Correct answer)
- Ether bond
- Carbonate bond
Correct answer: Ester bond
Ester bonds are used to mask carboxylic acids in prodrugs because esterases cleave them readily in vivo to regenerate the active acid.
Question 3: Which analytical technique is the gold standard for absolute stereochemical assignment in pharmaceutical compounds?
- Optical rotation polarimetry
- Chiral HPLC
- X-ray crystallography (Correct answer)
- Circular dichroism spectroscopy
Correct answer: X-ray crystallography
X-ray crystallography provides definitive absolute configuration by directly mapping atomic positions in space, including stereogenic centers.
Question 4: The Lipinski Rule of Five predicts which property of drug candidates?
- Metabolic stability
- Oral bioavailability (Correct answer)
- Blood-brain barrier penetration
- Renal clearance
Correct answer: Oral bioavailability
Lipinski's Rule of Five uses MW ≤500, H-bond donors ≤5, H-bond acceptors ≤10, and cLogP ≤5 to predict likely oral bioavailability.
Question 5: CYP3A4 is responsible for metabolizing approximately what percentage of marketed drugs?
- 10–15%
- 25–30%
- 50–60% (Correct answer)
- 75–80%
Correct answer: 50–60%
CYP3A4 is the most abundant hepatic cytochrome P450 and metabolizes approximately 50–60% of marketed pharmaceuticals.
Question 6: Which functional group transformation is performed by Phase II glucuronidation?
- Oxidation of aromatic rings
- Conjugation with UDP-glucuronic acid (Correct answer)
- Reduction of carbonyl groups
- Hydrolysis of amide bonds
Correct answer: Conjugation with UDP-glucuronic acid
UDP-glucuronosyltransferases (UGTs) catalyze conjugation of polar groups with UDP-glucuronic acid to increase water solubility for excretion.
Question 7: Which property of a drug most directly predicts its ability to cross the blood-brain barrier via passive diffusion?
- High molecular weight
- High lipophilicity and low polar surface area (Correct answer)
- High number of hydrogen bond donors
- Low plasma protein binding
Correct answer: High lipophilicity and low polar surface area
High lipophilicity (high logP) and low polar surface area (PSA < 60 Ų) favor passive transcellular diffusion across the blood-brain barrier.
MChem Master of Chemistry Master of Chemistry: Pharmaceutical Chemistry 2
Which pharmacokinetic parameter describes the fraction of an administered dose that reaches systemic circulation unchanged?