pH-Partition Hypothesis MCQs With Answer

Introduction: The pH-partition hypothesis is a foundational concept in biopharmaceutics and pharmacokinetics that explains how ionization of drugs influences their movement across biological membranes. For M.Pharm students, mastering this topic is essential to predict oral absorption, distribution into compartments (like placenta, milk, and brain), and renal excretion. This quiz set of 20 MCQs is designed to deepen understanding by integrating Henderson–Hasselbalch principles, ion trapping, and clinical implications such as urine pH manipulation and drug transfer across barriers. Questions range from conceptual to applied scenarios commonly encountered in drug development and clinical pharmacokinetics, allowing students to test and reinforce practical reasoning skills.

Q1. What is the core concept of the pH-partition hypothesis?

• Ionized form crosses lipid membranes more readily than unionized form
• Unionized form crosses lipid membranes more readily than ionized form
• Only charged molecules can diffuse through membranes
• Drug transport is independent of pH and ionization

Correct Answer: Unionized form crosses lipid membranes more readily than ionized form

Q2. Which Henderson–Hasselbalch equation correctly describes a weak acid?

• pH = pKa + log [A-]/[HA]
• pH = pKa + log [HA]/[A-]
• pH = pKa – log [A-]/[HA]
• pH = pKa – log [HA]/[A-]

Correct Answer: pH = pKa + log [A-]/[HA]

Q3. For a weak base, which form of Henderson–Hasselbalch expression is appropriate?

• pH = pKa + log [BH+]/[B]
• pH = pKa + log [B]/[BH+]
• pH = pKa – log [B]/[BH+]
• pH = pKa – log [BH+]/[B]

Correct Answer: pH = pKa + log [B]/[BH+]

Q4. A weak acid drug has pKa 4.5. In gastric fluid at pH 1.5, what is expected regarding its absorption?

• Absorption is favored because the drug is mostly ionized
• Absorption is favored because the drug is mostly unionized
• Absorption is reduced because the drug is highly protein bound
• Absorption is negligible due to large molecular size

Correct Answer: Absorption is favored because the drug is mostly unionized

Q5. Which statement best describes ion trapping?

• An ionized drug diffuses across membranes and becomes unionized in the new compartment
• A neutral drug becomes ionized after crossing a membrane and cannot readily cross back
• Protein binding traps drugs in plasma
• Lipid-soluble drugs are trapped inside cells by binding to intracellular proteins

Correct Answer: A neutral drug becomes ionized after crossing a membrane and cannot readily cross back

Q6. Considering the slightly acidic fetal plasma compared to maternal plasma, which drug class is most likely to accumulate in the fetus?

• Weak acids
• Neutral lipophilic drugs
• Weak bases
• Highly protein‑bound drugs

Correct Answer: Weak bases

Q7. To enhance renal excretion of a weak acidic drug, which urinary pH manipulation is appropriate?

• Acidify urine to pH 4–5
• Alkalinize urine to pH 8–9
• Maintain urine at neutral pH 7.0 only
• Urine pH has no effect on weak acid excretion

Correct Answer: Alkalinize urine to pH 8–9

Q8. Which clinical maneuver would increase urinary elimination of amphetamine (a weak base)?

• Administer sodium bicarbonate to alkalinize urine
• Administer ammonium chloride to acidify urine
• Give a diuretic that increases urine volume without pH change
• Give activated charcoal orally

Correct Answer: Administer ammonium chloride to acidify urine

Q9. For a weak acid drug, increasing the pH of the intestinal lumen (making it more alkaline) will most likely:

• Increase the fraction unionized and enhance absorption
• Decrease the fraction unionized and reduce membrane permeation
• Have no effect because only lipid solubility matters
• Convert the drug to a different chemical entity

Correct Answer: Decrease the fraction unionized and reduce membrane permeation

Q10. Which formula gives the fraction of a weak base that is unionized at a given pH?

• Fraction unionized = 1 / (1 + 10^(pKa – pH))
• Fraction unionized = 1 / (1 + 10^(pH – pKa))
• Fraction unionized = 10^(pKa – pH) / (1 + 10^(pKa – pH))
• Fraction unionized = 10^(pH – pKa) / (1 + 10^(pH – pKa))

Correct Answer: Fraction unionized = 1 / (1 + 10^(pKa – pH))

Q11. Which of the following is NOT a central element of the pH‑partition hypothesis?

• Membrane permeability of unionized species
• Ionization state as described by pKa and pH
• Transmembrane pH gradients causing ion trapping
• Degree of plasma protein binding determining ionization

Correct Answer: Degree of plasma protein binding determining ionization

Q12. Human breast milk has a slightly lower pH than plasma. According to pH‑partition, which drugs preferentially concentrate in milk?

• Weak acids
• Weak bases
• Strong electrolytes only
• Highly ionized molecules

Correct Answer: Weak bases

Q13. If a drug has pKa equal to the pH of its environment (pKa = pH), what is the expected fraction ionized?

• About 0% ionized
• About 25% ionized
• About 50% ionized
• About 100% ionized

Correct Answer: About 50% ionized

Q14. Which physicochemical properties most strongly determine a drug’s ability to cross lipid membranes according to pH‑partition theory?

• Molecular weight and water solubility only
• Lipophilicity and degree of ionization (unionized fraction)
• Chemical stability in gastric acid only
• Color and crystalline form

Correct Answer: Lipophilicity and degree of ionization (unionized fraction)

Q15. A weak base with pKa 9.0 is present in the stomach (pH 1.5). What is the expected stomach absorption?

• High absorption because the base is mostly unionized
• Low absorption because the base is mostly protonated (ionized)
• High absorption due to active transport mechanisms
• Complete degradation before absorption

Correct Answer: Low absorption because the base is mostly protonated (ionized)

Q16. Despite gastric pH differences, the small intestine is the major site for drug absorption mainly because:

• It has a higher fraction of unionized weak acids than the stomach
• It provides a much larger surface area and permeability for absorption
• It actively secretes drugs into circulation
• Drugs are always ionized in the stomach and neutral in the intestine

Correct Answer: It provides a much larger surface area and permeability for absorption

Q17. Aspirin (acetylsalicylic acid, pKa ≈ 3.5) is rapidly absorbed from the stomach because:

• The stomach pH keeps aspirin ionized and trapped there
• The stomach pH renders aspirin largely unionized allowing membrane diffusion
• Aspirin is actively transported into gastric mucosa
• Aspirin is a weak base and becomes unionized in stomach

Correct Answer: The stomach pH renders aspirin largely unionized allowing membrane diffusion

Q18. During systemic alkalosis (blood pH increases), which of the following is most likely?

• Increased CNS penetration of weak acids
• Increased CNS penetration of weak bases
• No change in drug distribution for weak bases
• All drugs become more protein bound

Correct Answer: Increased CNS penetration of weak bases

Q19. Which drug property best predicts rapid crossing of the blood–brain barrier under the pH‑partition concept?

• High ionization and low lipophilicity
• Predominantly unionized and high lipophilicity at brain pH
• Strong acidic character with high molecular weight
• Extensive plasma protein binding

Correct Answer: Predominantly unionized and high lipophilicity at brain pH

Q20. For enhancing urinary clearance of phenobarbital (a weak acid), which clinical intervention is appropriate?

• Acidify the urine with ammonium chloride
• Alkalinize the urine with sodium bicarbonate
• Administer lipid emulsions to sequester the drug
• Give probenecid to reduce renal secretion

Correct Answer: Alkalinize the urine with sodium bicarbonate

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