FPGEE Pharmaceutical Chemistry 5 — Questions and Answers
Question 1: Which analytical technique provides definitive molecular weight determination for a pharmaceutical compound?
- High-performance liquid chromatography (HPLC)
- Mass spectrometry (Correct answer)
- Infrared spectroscopy
- Potentiometric titration
Correct answer: Mass spectrometry
Mass spectrometry measures the mass-to-charge ratio (m/z) of ions, providing precise molecular weight and fragmentation pattern information.
Question 2: The chelation of metal ions by tetracycline antibiotics is clinically significant because:
- It increases drug bioavailability when taken with dairy
- It reduces absorption when taken with calcium, magnesium, or iron-containing products (Correct answer)
- It enhances renal elimination of the drug
- It activates the drug's antibacterial mechanism
Correct answer: It reduces absorption when taken with calcium, magnesium, or iron-containing products
Tetracyclines form insoluble chelate complexes with divalent and trivalent metal ions (Ca2+, Mg2+, Fe3+), significantly reducing oral absorption.
Question 3: Polymorphism in pharmaceutical solids refers to:
- Different salt forms of the same drug
- The ability of a compound to exist in more than one crystalline form (Correct answer)
- Isomers with the same molecular formula but different connectivity
- The conversion of a drug from solid to amorphous state
Correct answer: The ability of a compound to exist in more than one crystalline form
Polymorphs are different crystalline arrangements of the same molecule, which can differ in melting point, solubility, dissolution rate, and bioavailability.
Question 4: Which reaction is responsible for the yellow discoloration seen when phenothiazine drugs degrade?
- Hydrolysis of the phenothiazine ring
- Oxidation of the sulfur atom forming sulfoxides (Correct answer)
- Reduction of the aromatic system
- N-dealkylation of the side chain
Correct answer: Oxidation of the sulfur atom forming sulfoxides
Phenothiazines are oxidized at the sulfur atom to form sulfoxide metabolites and degradation products, producing characteristic colored compounds.
Question 5: The Hammett sigma (σ) constant in quantitative structure-activity relationship (QSAR) studies describes:
- Steric effects of substituents on a ring
- Electronic effects (electron-donating or electron-withdrawing) of aromatic substituents (Correct answer)
- Lipophilicity contribution of each substituent
- The molar refractivity of a substituent
Correct answer: Electronic effects (electron-donating or electron-withdrawing) of aromatic substituents
The Hammett σ constant quantifies the electronic effect of a substituent on an aromatic ring, with positive values indicating electron withdrawal and negative values indicating electron donation.
Question 6: Which type of covalent bond formation between a drug and its target is associated with irreversible inhibition?
- Hydrogen bond formation
- Van der Waals interaction
- Alkylation of a nucleophilic residue (Correct answer)
- Ionic interaction with charged amino acids
Correct answer: Alkylation of a nucleophilic residue
Covalent alkylation of nucleophilic residues (e.g., cysteine, serine) by reactive drug electrophiles creates a permanent drug-protein bond, irreversibly inhibiting the target.
Question 7: In the context of drug stability, photolysis most commonly affects drugs containing:
- Saturated aliphatic chains
- Aromatic rings and conjugated double-bond systems (Correct answer)
- Quaternary ammonium groups
- Simple alkyl halides
Correct answer: Aromatic rings and conjugated double-bond systems
Drugs with aromatic rings and conjugated pi systems absorb UV/visible light, making them prone to photochemical degradation reactions.
FPGEE Pharmaceutical Chemistry 5
Which analytical technique provides definitive molecular weight determination for a pharmaceutical compound?