Complexation and drug action MCQs With Answer

Complexation and drug action MCQs with Answer are essential study tools for B. Pharm students preparing for exams in pharmaceutics, medicinal chemistry and pharmacokinetics. This focused set covers key concepts such as drug–ligand coordination, metal chelation, inclusion complexes (e.g., cyclodextrins), stability (formation) constants, effects on solubility, bioavailability, drug stability and therapeutic activity. Questions also explore analytical methods (Job’s plot, Benesi–Hildebrand, spectrophotometry), complexometric titration, and clinical implications like tetracycline–calcium interactions and metal-based drugs such as cisplatin. Designed to deepen understanding and improve exam readiness, these MCQs emphasize real-world examples and mechanism-based reasoning. Now let’s test your knowledge with 50 MCQs on this topic.

Q1. What is complexation in the context of pharmaceutical chemistry?

• A covalent bond formation between two drug molecules
• The reversible association between a drug and a ligand via coordinate or non-covalent interactions
• Permanent chemical modification of a drug to form a prodrug
• Physical mixing of drug with excipients without interaction

Correct Answer: The reversible association between a drug and a ligand via coordinate or non-covalent interactions

Q2. Which of the following is a common inclusion complex used to enhance drug solubility?

• EDTA
• Cyclodextrin
• Sodium chloride
• Magnesium stearate

Correct Answer: Cyclodextrin

Q3. A high formation (stability) constant (Kf) for a drug–metal complex indicates:

• Low affinity between drug and metal
• High affinity and greater stability of the complex
• Rapid dissociation in biological fluids
• No effect on bioavailability

Correct Answer: High affinity and greater stability of the complex

Q4. Which technique is commonly used to determine the stoichiometry of a drug–ligand complex?

• IR spectroscopy only
• Job’s method (continuous variation)
• Thermal gravimetric analysis
• X-ray diffraction for stoichiometry exclusively

Correct Answer: Job’s method (continuous variation)

Q5. Benesi–Hildebrand analysis is primarily applied to determine:

• Rate constants of irreversible reactions
• Formation constant for 1:1 complexes using spectrophotometric data
• Stoichiometry of polymeric complexes
• Melting point of complexes

Correct Answer: Formation constant for 1:1 complexes using spectrophotometric data

Q6. Which drug class is well-known for chelating divalent cations like calcium and iron?

• Beta-lactam antibiotics
• Tetracyclines
• Statins
• Antihistamines

Correct Answer: Tetracyclines

Q7. Complexation with cyclodextrin mainly improves drug properties by:

• Forming covalent adducts with proteins
• Increasing solubility and stability via inclusion of hydrophobic moieties
• Increasing drug molecular weight irreversibly
• Destroying drug crystal lattice permanently

Correct Answer: Increasing solubility and stability via inclusion of hydrophobic moieties

Q8. EDTA is used pharmaceutically as a:

• Solubilizing agent for hydrophobic drugs
• Complexing agent to sequester metal ions
• Surface-active preservative
• Tablet binder

Correct Answer: Complexing agent to sequester metal ions

Q9. Metal-based anticancer drug example that acts via coordination complex formation is:

• Ibuprofen
• Cisplatin
• Amoxicillin
• Metformin

Correct Answer: Cisplatin

Q10. How does complexation typically affect the oral bioavailability of a drug that forms a stable insoluble complex in the gut?

• Bioavailability increases due to enhanced absorption
• Bioavailability decreases due to reduced free drug available for absorption
• No change because complexes do not affect absorption
• Bioavailability changes unpredictably without relation to complexation

Correct Answer: Bioavailability decreases due to reduced free drug available for absorption

Q11. Which parameter is directly related to Gibbs free energy (ΔG°) for complex formation?

• Equilibrium constant (Kf) via ΔG° = -RT ln Kf
• Molecular weight of the ligand only
• pH of the solution only
• Viscosity of the medium

Correct Answer: Equilibrium constant (Kf) via ΔG° = -RT ln Kf

Q12. Protein binding of drugs can be considered a form of complexation. Which plasma protein predominantly binds acidic drugs?

• α1-acid glycoprotein
• Albumin
• Globulin
• Fibrinogen

Correct Answer: Albumin

Q13. A 1:2 drug:metal complex indicates which stoichiometry?

• One metal to two drug molecules
• One drug to two metal ions
• Two drugs to two metals
• Stoichiometry cannot be defined

Correct Answer: One drug to two metal ions

Q14. Which analytical method measures complex formation by monitoring absorbance change with ligand concentration?

• UV-Visible spectrophotometry
• Gas chromatography
• Polarimetry
• Osmometry

Correct Answer: UV-Visible spectrophotometry

Q15. Masking agents in complexometric titration are used to:

• Enhance precipitation of metal ions
• Temporarily prevent certain metal ions from reacting with titrant
• Act as pH indicators
• Increase turbidity for endpoint detection

Correct Answer: Temporarily prevent certain metal ions from reacting with titrant

Q16. Complexation can alter drug distribution by:

• Changing lipophilicity and plasma protein binding
• Only changing the drug’s color
• Only increasing renal clearance always
• Having no effect on tissue penetration

Correct Answer: Changing lipophilicity and plasma protein binding

Q17. Which factor commonly affects the stability of metal–drug complexes?

• Atmospheric pressure only
• pH, ionic strength and competing ligands
• Tablet hardness only
• Color of the solution

Correct Answer: pH, ionic strength and competing ligands

Q18. Inclusion complexation with cyclodextrins occurs primarily through:

• Covalent bonding of drug to cyclodextrin
• Non-covalent encapsulation of hydrophobic moiety in the cyclodextrin cavity
• Oxidation of the drug
• Polymerization of the drug molecule

Correct Answer: Non-covalent encapsulation of hydrophobic moiety in the cyclodextrin cavity

Q19. Which of the following drugs demonstrates reduced absorption when co-administered with antacids containing magnesium or aluminum?

• Paracetamol
• Tetracycline
• Insulin (subcutaneous)
• Nitroglycerin (sublingual)

Correct Answer: Tetracycline

Q20. The method of continuous variation (Job’s plot) requires varying:

• Total concentration while keeping mole fraction constant
• Mole fraction of components while keeping total concentration constant
• Temperature only
• pH only

Correct Answer: Mole fraction of components while keeping total concentration constant

Q21. Complexometric titration commonly uses which titrant to determine metal ion concentration?

• Hydrochloric acid
• EDTA (ethylenediaminetetraacetic acid)
• Acetone
• Sodium lauryl sulfate

Correct Answer: EDTA (ethylenediaminetetraacetic acid)

Q22. Which statement about drug–excipient complexation is true?

• Complexation never alters drug release from dosage forms
• Complexation can affect stability, solubility and release profile
• Excipients cannot form complexes with drugs
• Complexation always improves drug stability

Correct Answer: Complexation can affect stability, solubility and release profile

Q23. Chelation therapy is used clinically to:

• Bind and enhance absorption of essential metals
• Remove toxic metal ions from the body
• Stabilize cyclodextrin complexes only
• Slow down drug metabolism irreversibly

Correct Answer: Remove toxic metal ions from the body

Q24. Which technique can directly provide structural information about a drug–metal complex?

• NMR spectroscopy
• pH meter
• UV lamp only
• Visual inspection

Correct Answer: NMR spectroscopy

Q25. Complexation that increases drug lipophilicity would most likely:

• Decrease tissue penetration
• Increase membrane permeability and tissue distribution
• Eliminate first-pass metabolism completely
• Have no impact on pharmacokinetics

Correct Answer: Increase membrane permeability and tissue distribution

Q26. Which property is most improved by forming an inclusion complex with cyclodextrin for a hydrophobic drug?

• Melting point
• Water solubility and dissolution rate
• Color brilliance
• Density

Correct Answer: Water solubility and dissolution rate

Q27. A ligand that donates an electron pair to a metal ion to form a coordinate bond is called:

• An electrophile
• A nucleophile or donor ligand
• An oxidizing agent only
• An inert gas

Correct Answer: A nucleophile or donor ligand

Q28. Which of the following increases the apparent solubility of a poorly soluble drug by complexation?

• Formation of an insoluble salt
• Complexation with cyclodextrins or surfactants
• Evaporation of solvent
• Crystallization into larger crystals

Correct Answer: Complexation with cyclodextrins or surfactants

Q29. In competitive complexation, the presence of another ligand that has higher affinity will:

• Enhance stability of the original complex
• Displace the drug from the complex leading to alteration in free drug concentration
• Have no effect on drug action
• Make the system inert

Correct Answer: Displace the drug from the complex leading to alteration in free drug concentration

Q30. Which example illustrates complexation affecting drug action adversely?

• Cyclodextrin increasing solubility of loratadine
• Tetracycline binding to dietary calcium reducing absorption
• PEGylation improving circulation time
• Prodrug conversion to active form

Correct Answer: Tetracycline binding to dietary calcium reducing absorption

Q31. A drug forms a colored complex with metal ion and the absorbance increases linearly with metal concentration. This suggests:

• No complex formation
• Use of spectrophotometry for quantitative analysis
• That titration is impossible
• That complex is non-stoichiometric

Correct Answer: Use of spectrophotometry for quantitative analysis

Q32. Macrocyclic ligands often form very stable complexes due to:

• Low ring strain and preorganized donor sites (macrocyclic effect)
• High flexibility only
• Hydrophobic aggregation only
• Large molecular weight only

Correct Answer: Low ring strain and preorganized donor sites (macrocyclic effect)

Q33. Which effect is expected if a drug is sequestered by plasma proteins forming a strong complex?

• Increased free concentration and enhanced effect
• Decreased free concentration and reduced pharmacologic effect
• Immediate renal excretion of free drug
• Conversion into an active metabolite

Correct Answer: Decreased free concentration and reduced pharmacologic effect

Q34. The term ‘chelate’ refers to:

• A ligand that forms multiple bonds to a single metal ion creating a ring structure
• A single-point hydrogen bond
• Only interactions with proteins
• A non-binding physical mixture

Correct Answer: A ligand that forms multiple bonds to a single metal ion creating a ring structure

Q35. Which property is measured to determine the formation constant using spectrophotometry?

• Absorbance change as a function of ligand or metal concentration
• Viscosity change only
• Boiling point elevation
• Conductivity at zero concentration

Correct Answer: Absorbance change as a function of ligand or metal concentration

Q36. Which of the following drugs forms complexes with iron affecting iron-based assays?

• Paracetamol
• Tetracycline and some phenolic drugs
• Insulin
• Glucose

Correct Answer: Tetracycline and some phenolic drugs

Q37. Formation of complexes can protect a drug from degradation. This is called:

• Complexation-induced degradation
• Stabilization by complexation or protective complexation
• Complete inactivation
• Buffering only

Correct Answer: Stabilization by complexation or protective complexation

Q38. Which analytical plot helps determine 1:1 complex formation by linearizing absorbance data?

• Benesi–Hildebrand plot
• Van’t Hoff plot only
• Arrhenius plot only
• Henderson–Hasselbalch plot

Correct Answer: Benesi–Hildebrand plot

Q39. A drug forms a labile complex with metal ions. ‘Labile’ implies:

• Complex is very stable and inert
• Complex undergoes rapid exchange with ligands and dissociates readily
• Complex cannot be detected analytically
• Complex formation is irreversible

Correct Answer: Complex undergoes rapid exchange with ligands and dissociates readily

Q40. Which complexation is deliberately used to deliver hydrophobic drugs in aqueous formulations?

• Formation of insoluble salts
• Inclusion complexes with cyclodextrins or micellar solubilization
• Chelation with toxic metals
• Formation of covalent polymer-drug conjugates only

Correct Answer: Inclusion complexes with cyclodextrins or micellar solubilization

Q41. The primary binding site for basic drugs in plasma is:

• Albumin
• α1-acid glycoprotein
• Globulin
• Fibrinogen

Correct Answer: α1-acid glycoprotein

Q42. Which factor would decrease the measured stability constant of a metal–ligand complex experimentally?

• Presence of competing ligands that bind the metal
• Lowering temperature for exothermic complexation
• Purifying reagents to remove contaminants
• Using higher pathlength cuvette in spectrophotometry

Correct Answer: Presence of competing ligands that bind the metal

Q43. Inclusion complex formation is typically driven by which primary interaction?

• Strong covalent bonding
• Hydrophobic interactions and van der Waals forces
• Formation of ionic crystals
• Covalent polymerization

Correct Answer: Hydrophobic interactions and van der Waals forces

Q44. Which drug’s therapeutic efficacy is an example of coordination chemistry in action (metal complex as active drug)?

• Cisplatin (platinum complex)
• Aspirin (salicylate)
• Metformin (biguanide)
• Levothyroxine (iodinated amino acid)

Correct Answer: Cisplatin (platinum complex)

Q45. The presence of salt (ionic strength) in solution often influences complex formation by:

• Having no measurable effect
• Screening electrostatic interactions and altering activity coefficients
• Converting complexes into covalent bonds
• Instantly precipitating all complexes

Correct Answer: Screening electrostatic interactions and altering activity coefficients

Q46. Which method can distinguish between different stoichiometries (1:1 vs 1:2) of complexes?

• Job’s plot combined with spectrophotometric titration
• Only melting point determination
• Macroscopic observation of color only
• Flame test exclusively

Correct Answer: Job’s plot combined with spectrophotometric titration

Q47. Drug–cyclodextrin complexes may reduce drug irritation by:

• Masking unpleasant taste and local irritation through inclusion
• Forming toxic metabolites
• Increasing local free drug concentration only
• Inducing immediate precipitation at the site

Correct Answer: Masking unpleasant taste and local irritation through inclusion

Q48. Which descriptor best characterizes a ligand that forms many bonds to a metal via different donor atoms?

• Monodentate ligand
• Polydentate (chelate) ligand
• Inert gas ligand
• Hydrophobic ligand only

Correct Answer: Polydentate (chelate) ligand

Q49. In formulation, complexation with certain excipients can be used to control release. This approach is known as:

• Immediate release formulation only
• Complexation-based controlled or sustained release
• Only taste masking unrelated to release
• Lyophilization

Correct Answer: Complexation-based controlled or sustained release

Q50. Which is a potential risk of strong drug–metal complex formation in patients?

• Improved drug taste only
• Reduced therapeutic effect, altered distribution, or toxicity due to metal interactions
• Guaranteed increased efficacy without side effects
• Complete elimination of side effects always

Correct Answer: Reduced therapeutic effect, altered distribution, or toxicity due to metal interactions

G S Sachin

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.

Mail- Sachin@pharmacyfreak.com