Partition coefficient (P) and related terms like log P and log D describe drug lipophilicity—the tendency of a molecule to distribute between an organic phase (usually octanol) and water. For B. Pharm students, mastering partition coefficient concepts, measurement methods (shake‑flask, HPLC, potentiometric), and computational estimates (CLogP, Hansch analysis) is essential to predict absorption, permeability, distribution, blood‑brain barrier penetration, and bioavailability. Understanding pH‑dependent ionization (pKa), solvent effects, temperature, and experimental pitfalls helps optimize formulation, ADME profiling, and therapeutic design. Now let’s test your knowledge with 30 MCQs on this topic.
Q1. What is the partition coefficient (P) for a non‑ionized drug?
- The ratio of drug concentration in octanol to that in water
- The ratio of drug concentration in water to that in octanol
- The difference between concentrations in octanol and water
- The sum of concentrations in octanol and water
Correct Answer: The ratio of drug concentration in octanol to that in water
Q2. What does log P represent?
- The base‑10 logarithm of the partition coefficient
- The natural logarithm of the distribution coefficient
- The pH at which the drug is 50% ionized
- The ratio of ionized to unionized drug
Correct Answer: The base‑10 logarithm of the partition coefficient
Q3. How does log D differ from log P?
- Log D is the distribution coefficient at a specific pH including ionized and unionized species
- Log D is the partition coefficient for pure octanol only
- Log P includes ionized species while log D excludes them
- Log D is the logarithm of permeability across a membrane
Correct Answer: Log D is the distribution coefficient at a specific pH including ionized and unionized species
Q4. Which solvent pair is most commonly used to define the classical partition coefficient?
- Octanol and water
- Benzene and water
- Hexane and buffer
- Chloroform and methanol
Correct Answer: Octanol and water
Q5. What are the units of the partition coefficient (P)?
- Unitless (ratio)
- Moles per liter
- Liters per mole
- mg/mL
Correct Answer: Unitless (ratio)
Q6. How does ionization of a drug affect its partitioning into octanol?
- Ionized species preferentially remain in the aqueous phase
- Ionized species preferentially partition into octanol
- Ionization has no effect on partitioning
- Ionization always increases log P
Correct Answer: Ionized species preferentially remain in the aqueous phase
Q7. Which experimental method is the classical reference for measuring partition coefficient?
- Shake‑flask method
- Mass spectrometry only
- NMR spectroscopy exclusively
- DSC thermal analysis
Correct Answer: Shake‑flask method
Q8. How is reversed‑phase HPLC used in lipophilicity estimation?
- Retention time correlates with lipophilicity and can be converted to log P
- It directly measures octanol concentration only
- It measures pKa but not lipophilicity
- HPLC cannot be used for lipophilicity estimation
Correct Answer: Retention time correlates with lipophilicity and can be converted to log P
Q9. For a weak base with pKa 8.5 at pH 7.4, how will log D at pH 7.4 compare to log P?
- Log D will be lower than log P because the base is partially ionized
- Log D will be equal to log P
- Log D will be higher than log P
- Log D is unrelated to pH and equals log P
Correct Answer: Log D will be lower than log P because the base is partially ionized
Q10. What does a high log P value generally indicate about a drug?
- High lipophilicity and lower aqueous solubility
- High aqueous solubility and low membrane permeability
- Strong ionization at physiological pH
- Requirement for intravenous dosing only
Correct Answer: High lipophilicity and lower aqueous solubility
Q11. Which log P range is often considered favorable for oral absorption (rule‑of‑thumb)?
- Approximately 0 to 3
- Greater than 6
- Less than −2
- Exactly equal to 5
Correct Answer: Approximately 0 to 3
Q12. How does increased lipophilicity affect passive blood‑brain barrier (BBB) penetration?
- It generally increases passive BBB penetration up to an optimum
- It always prevents BBB penetration
- It has no effect on BBB penetration
- It converts the drug into a P‑glycoprotein substrate
Correct Answer: It generally increases passive BBB penetration up to an optimum
Q13. What does the Hansch equation relate in medicinal chemistry?
- Biological activity to lipophilicity (log P) and electronic factors
- Temperature dependence of solubility only
- Partition coefficient to molecular weight exclusively
- Permeability to buffer composition
Correct Answer: Biological activity to lipophilicity (log P) and electronic factors
Q14. Does temperature affect measured partition coefficients?
- Yes; partitioning is temperature‑dependent
- No; partition coefficients are invariant with temperature
- Only pH affects partition coefficients
- Only solvent purity affects partition coefficients
Correct Answer: Yes; partitioning is temperature‑dependent
Q15. What is a common experimental limitation of the shake‑flask method?
- Emulsion formation and slow equilibration can bias results
- It cannot detect neutral species
- It always overestimates aqueous concentration by a fixed factor
- It requires radiolabeled drug exclusively
Correct Answer: Emulsion formation and slow equilibration can bias results
Q16. What is CLogP?
- A computational estimate of log P based on molecular structure
- An experimental HPLC retention time value
- The pKa of a compound determined potentiometrically
- The concentration of drug in the octanol phase
Correct Answer: A computational estimate of log P based on molecular structure
Q17. Which method can estimate log P for ionizable compounds by pH titration?
- Potentiometric method
- UV melting point analysis
- Gas chromatography of salts
- Differential scanning calorimetry
Correct Answer: Potentiometric method
Q18. Does the octanol‑water partition coefficient directly measure plasma protein binding?
- No; P is measured in octanol/water and does not include plasma proteins
- Yes; P equals plasma protein binding percentage
- Only for basic drugs is P equal to protein binding
- P directly measures albumin binding affinity
Correct Answer: No; P is measured in octanol/water and does not include plasma proteins
Q19. Which factor can cause systematic error when measuring log P experimentally?
- Presence of surfactants that form micelles
- Using ultrapure octanol without mixing
- Measuring at 0.1°C only
- Using glassware cleaned with water only
Correct Answer: Presence of surfactants that form micelles
Q20. How does increasing lipophilicity generally influence passive permeability across cell membranes?
- Permeability generally increases with lipophilicity up to an optimum
- Permeability decreases linearly with lipophilicity
- Permeability is independent of lipophilicity
- Permeability always becomes zero for lipophilic drugs
Correct Answer: Permeability generally increases with lipophilicity up to an optimum
Q21. For a weak acid (pKa 4.5) at pH 7.4, how does log D compare to log P?
- Log D will be much lower than log P because the acid is mostly ionized
- Log D equals log P at all pH values
- Log D will be higher than log P
- Log D is irrelevant for acids
Correct Answer: Log D will be much lower than log P because the acid is mostly ionized
Q22. When does the distribution coefficient (D) equal the partition coefficient (P) for an ionizable drug?
- When the drug is completely non‑ionized at that pH
- When the drug has very high molecular weight
- Only at pH 14
- When protein binding is 100%
Correct Answer: When the drug is completely non‑ionized at that pH
Q23. Why is octanol used as a surrogate for biological membranes?
- Because octanol mimics the hydrophobic core and partitioning behavior of lipid bilayers
- Because octanol is chemically identical to phospholipids
- Because octanol forms micelles like proteins
- Because octanol is highly ionic
Correct Answer: Because octanol mimics the hydrophobic core and partitioning behavior of lipid bilayers
Q24. If log P = 2, what is the partition coefficient P?
- P = 100
- P = 2
- P = 0.01
- P = 10
Correct Answer: P = 100
Q25. A negative log P value indicates which preference?
- Preference for the aqueous phase over octanol
- Preference for octanol over water
- Equal distribution between phases
- That the compound is a gas at room temperature
Correct Answer: Preference for the aqueous phase over octanol
Q26. Which chromatographic approach is commonly correlated with log P values?
- Reversed‑phase HPLC retention measurements
- Size‑exclusion chromatography of salts
- Ion‑exchange chromatography without pH control
- Gas chromatography of ionic compounds
Correct Answer: Reversed‑phase HPLC retention measurements
Q27. Which experimental parameter can speed equilibration in shake‑flask measurements?
- Increased mixing (stirring or shaking intensity)
- Lowering temperature to near freezing
- Adding excess solid drug without mixing
- Using closed vials without phase contact
Correct Answer: Increased mixing (stirring or shaking intensity)
Q28. Why should surfactants be avoided in standard partition coefficient measurements?
- They form micelles and alter true partitioning between octanol and water
- They increase the volatility of octanol
- They convert octanol into a polar solvent
- They reduce the pH to zero
Correct Answer: They form micelles and alter true partitioning between octanol and water
Q29. How can high lipophilicity influence formulation strategy?
- May require lipid‑based formulations or solubilization strategies
- Always allows aqueous immediate‑release tablets without modification
- Makes the compound incompatible with all excipients
- Ensures 100% oral bioavailability
Correct Answer: May require lipid‑based formulations or solubilization strategies
Q30. Which expression gives log D for a monoprotic weak acid at a given pH?
- log D = log P − log(1 + 10^(pH − pKa))
- log D = log P + log(1 + 10^(pH − pKa))
- log D = log P × (pH − pKa)
- log D = pKa − pH
Correct Answer: log D = log P − log(1 + 10^(pH − pKa))
I am a Registered Pharmacist under the Pharmacy Act, 1948, and the founder of PharmacyFreak.com. I hold a Bachelor of Pharmacy degree from Rungta College of Pharmaceutical Science and Research. With a strong academic foundation and practical knowledge, I am committed to providing accurate, easy-to-understand content to support pharmacy students and professionals. My aim is to make complex pharmaceutical concepts accessible and useful for real-world application.
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