Chiral separations using CSPs MCQs With Answer

Chiral separations using CSPs MCQs With Answer

Chiral separations are essential in pharmaceutical analysis because enantiomers can differ dramatically in pharmacology and safety. This quiz collection focuses on chiral stationary phases (CSPs) used in liquid and gas chromatography, covering principles of chiral recognition, common CSP families (polysaccharide derivatives, macrocyclic antibiotics, cyclodextrins, Pirkle-type and ligand-exchange), method development variables, and scale-up strategies like preparative and simulated moving bed approaches. Designed for M.Pharm students taking Advanced Instrumental Analysis (MPA 201T), the 20 MCQs reinforce theoretical understanding and practical decision-making for selecting selectors, mobile phase modifiers, temperature considerations, and detection strategies in real-world chiral separations.

Q1. What is the primary function of a chiral stationary phase (CSP) in chromatographic separations?

• To increase column backpressure for better separation
• To separate enantiomers by differential reversible interactions with the stationary phase
• To derivatize analytes into diastereomers during chromatography
• To act as an inert support for achiral separations

Correct Answer: To separate enantiomers by differential reversible interactions with the stationary phase

Q2. Which class of CSPs is most widely used in high-performance liquid chromatography for broad-range enantiomer separations?

• Polysaccharide-based CSPs (e.g., cellulose or amylose derivatives)
• Pirkle-type (brush-type) small-molecule selectors
• Cyclodextrin-coated capillaries
• Silica-based achiral reversed-phase materials

Correct Answer: Polysaccharide-based CSPs (e.g., cellulose or amylose derivatives)

Q3. Which model best describes the molecular recognition responsible for enantioselective retention on many CSPs?

• Single-point ionic interaction model
• Three-point (or multipoint) interaction model involving simultaneous interactions
• Pure size-exclusion model
• Irreversible covalent bonding model

Correct Answer: Three-point (or multipoint) interaction model involving simultaneous interactions

Q4. Vancomycin is used as the chiral selector in which type of CSP?

• Polysaccharide-derived CSP
• Macrocyclic glycopeptide (macrocyclic antibiotic) CSP
• Pirkle-type (brush) CSP
• Cyclodextrin-based CSP

Correct Answer: Macrocyclic glycopeptide (macrocyclic antibiotic) CSP

Q5. Cyclodextrin-based chiral selectors are most traditionally employed in which chromatographic technique?

• Size-exclusion chromatography
• Gas chromatography (GC) on chiral capillary columns
• Ion-exchange chromatography
• Supercritical fluid extraction

Correct Answer: Gas chromatography (GC) on chiral capillary columns

Q6. Pirkle-type CSPs are commonly described using which alternative name?

• Macrocyclic selector CSPs
• Brush-type chiral stationary phases
• Ion-exchange chiral phases
• Inclusion complex CSPs

Correct Answer: Brush-type chiral stationary phases

Q7. Which mobile phase additive is commonly used to reduce tailing and improve enantioseparation of basic analytes on silica-based CSPs?

• Trifluoroacetic acid (TFA)
• Diethylamine (DEA)
• Ethanol only without additives
• Sodium chloride

Correct Answer: Diethylamine (DEA)

Q8. How does increasing column temperature generally affect enantioselectivity (α) on most CSPs?

• It always increases selectivity due to faster kinetics
• It usually decreases selectivity because differential binding is weakened
• It converts enantiomers into diastereomers
• It has no effect on selectivity

Correct Answer: It usually decreases selectivity because differential binding is weakened

Q9. Enantioselectivity (α) in chromatography is defined as which ratio?

• The ratio of retention times tR1/tR2
• The ratio of retention factors k’ for the two enantiomers (k’2/k’1)
• The ratio of column dead time to retention time
• The ratio of peak areas of two enantiomers

Correct Answer: The ratio of retention factors k’ for the two enantiomers (k’2/k’1)

Q10. Which detector provides direct chiral discrimination (response difference) without requiring prior chromatographic separation?

• UV absorbance detector
• Mass spectrometer (MS)
• Circular dichroism (CD) detector
• Evaporative light scattering detector (ELSD)

Correct Answer: Circular dichroism (CD) detector

Q11. Which feature of immobilized polysaccharide-based CSPs makes them especially versatile for method development?

• They are more fragile and require aqueous mobile phases only
• Covalent immobilization allows use of a broad range of organic solvents
• They cannot tolerate polar solvents
• They only work under reversed-phase conditions

Correct Answer: Covalent immobilization allows use of a broad range of organic solvents

Q12. Converting enantiomers into diastereomers for separation on achiral columns is achieved by which strategy?

• Using chiral stationary phases only
• Using chiral derivatizing agents to form diastereomeric derivatives
• Adding ionic salts to the mobile phase
• Decreasing column temperature to cryogenic levels

Correct Answer: Using chiral derivatizing agents to form diastereomeric derivatives

Q13. In ligand-exchange CSPs for amino acids, which central metal ion is most commonly employed?

• Calcium(II)
• Copper(II)
• Sodium(I)
• Iron(III)

Correct Answer: Copper(II)

Q14. Which statement about enantiomer elution order (EEO) is correct?

• EEO is fixed for a given analyte regardless of mobile phase or temperature
• EEO can change with mobile phase composition, temperature, or different CSPs
• EEO depends only on the detector used
• EEO is predictable purely from molecular weight

Correct Answer: EEO can change with mobile phase composition, temperature, or different CSPs

Q15. What is the correct formula for the capacity factor (k’) of a chromatographic peak?

• k’ = t0 / (tR – t0)
• k’ = (tR – t0) / t0
• k’ = tR × t0
• k’ = tR / t0

Correct Answer: k’ = (tR – t0) / t0

Q16. Macrocyclic antibiotic CSPs (e.g., teicoplanin, vancomycin) are particularly effective for separating which class of analytes?

• Nonpolar hydrocarbons exclusively
• Polar and amphoteric molecules such as amino acids, peptides, and pharmaceuticals
• Only inorganic ions
• Large proteins over 100 kDa

Correct Answer: Polar and amphoteric molecules such as amino acids, peptides, and pharmaceuticals

Q17. Which stationary phase packing parameter most directly improves column efficiency for chiral separations when reduced?

• Column internal diameter
• Particle size of the stationary phase (smaller gives higher efficiency)
• Macrocyclic selector molecular weight
• Column frit porosity

Correct Answer: Particle size of the stationary phase (smaller gives higher efficiency)

Q18. The chromatographic resolution (Rs) between two enantiomer peaks is given by which expression?

• Rs = (tR1 + tR2) / 2
• Rs = 2 × (tR2 – tR1) / (w1 + w2)
• Rs = (w1 – w2) / (tR2 – tR1)
• Rs = k’1 / k’2

Correct Answer: Rs = 2 × (tR2 – tR1) / (w1 + w2)

Q19. For large-scale preparative chiral separations to produce enantiomerically pure drug substances, which technique is commonly employed?

• Standard analytical HPLC with 4.6 mm ID columns
• Simulated moving bed (SMB) chromatography using chiral stationary phases
• Capillary electrophoresis with achiral buffers
• Thin-layer chromatography (TLC)

Correct Answer: Simulated moving bed (SMB) chromatography using chiral stationary phases

Q20. Which of the following is NOT considered a primary reversible interaction mechanism responsible for chiral recognition on CSPs?

• Hydrogen bonding
• Ionic interactions
• Covalent bonding
• π-π interactions

Correct Answer: Covalent bonding

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