Factors affecting resolution MCQs With Answer

Factors Affecting Resolution MCQs With Answer

Resolution is the cornerstone of reliable quantitation and identification in Modern Pharmaceutical Analytical Techniques. Whether you use HPLC, UHPLC, GC, CE, or UV-Vis, understanding how efficiency, selectivity, and retention interplay is vital for separating closely eluting analytes, stability-indicating methods, impurity profiling, and chiral analysis. This quiz dives into practical levers—particle size, column length, flow rate, temperature, pH, ionic strength, gradient slope, injection volume, extra-column effects, and detector settings—that directly affect resolution. Designed for M.Pharm students, the questions emphasize mechanism-based reasoning and method optimization choices you make at the bench. Use these MCQs to strengthen your grasp on why small changes in selectivity often beat brute-force increases in efficiency, and how to tune conditions for robust, high-resolution separations.

Q1. In chromatography, which set of parameters fundamentally determines resolution (Rs)?

• Efficiency (number of theoretical plates), selectivity (α), and retention factor (k’)
• Capacity factor, detector sensitivity, and injection volume
• Flow rate, sample polarity, and UV cut-off
• Column temperature, pump pulsation, and stationary-phase bleed

Correct Answer: Efficiency (number of theoretical plates), selectivity (α), and retention factor (k’)

Q2. If column length is doubled while keeping all other conditions identical, the resolution will approximately:

• Double
• Increase by the square root of 2
• Decrease by half
• Remain unchanged

Correct Answer: Increase by the square root of 2

Q3. Which change most directly improves column efficiency (N) and thus resolution, without intentionally changing selectivity?

• Decrease particle size from 5 µm to 3 µm
• Switch to a longer detection wavelength
• Increase injection volume
• Use a higher organic modifier percentage

Correct Answer: Decrease particle size from 5 µm to 3 µm

Q4. In isocratic RP-HPLC, which retention factor (k’) range generally provides the best practical resolution within reasonable analysis time?

• 0.2–0.8
• 1–2
• 2–10
• >15

Correct Answer: 2–10

Q5. For two peaks with poor separation, which strategy most effectively increases resolution by altering selectivity (α)?

• Change stationary-phase chemistry (e.g., C18 to phenyl-hexyl)
• Increase flow rate to the van Deemter minimum
• Increase column length by 25%
• Add a guard column of the same chemistry

Correct Answer: Change stationary-phase chemistry (e.g., C18 to phenyl-hexyl)

Q6. A weak acid (pKa = 4) in RP-HPLC is poorly resolved from its conjugate base. At which pH is higher retention and better resolution most likely?

• pH 2.5
• pH 4.0
• pH 6.0
• pH 8.0

Correct Answer: pH 2.5

Q7. Increasing column temperature from 25°C to 40°C in RP-HPLC (same mobile phase) tends to:

• Reduce mobile phase viscosity and plate height, potentially increasing resolution
• Increase k’ dramatically and lengthen the run substantially
• Always improve selectivity for isomers
• Cause cavitation and worsen peak shape in modern systems

Correct Answer: Reduce mobile phase viscosity and plate height, potentially increasing resolution

Q8. According to the van Deemter relationship, which statement about flow rate and resolution is most accurate?

• Operating at the flow that minimizes plate height yields maximal resolution
• Maximum resolution occurs at the highest achievable flow rate
• Resolution is independent of flow rate
• Doubling flow rate always doubles resolution

Correct Answer: Operating at the flow that minimizes plate height yields maximal resolution

Q9. Which practice most commonly degrades resolution for early-eluting peaks in RP-HPLC?

• Injecting the sample in a solvent stronger than the mobile phase
• Using longer column equilibration times
• Filtering samples through 0.2 µm membranes
• Maintaining column temperature with a column oven

Correct Answer: Injecting the sample in a solvent stronger than the mobile phase

Q10. Two peaks with α ≈ 1.02 coelute in an isocratic RP method. Which change is most likely to produce the largest resolution gain?

• Switching organic modifier type (e.g., acetonitrile to methanol) to alter selectivity
• Increasing flow rate by 20%
• Raising injection volume
• Extending total run time with a steeper gradient

Correct Answer: Switching organic modifier type (e.g., acetonitrile to methanol) to alter selectivity

Q11. To minimize extra-column band broadening in UHPLC and preserve resolution, the best approach is to:

• Use shorter, narrow-bore tubing and a low-volume detector cell
• Switch to larger-ID tubing to reduce backpressure
• Add a mixing tee between the column and detector
• Increase autosampler loop volume

Correct Answer: Use shorter, narrow-bore tubing and a low-volume detector cell

Q12. In ion-pair chromatography, adding an ion-pair reagent primarily improves resolution by modifying:

• Selectivity by changing effective analyte hydrophobicity
• Detector noise characteristics
• Pump pulsation amplitude
• Column temperature stability

Correct Answer: Selectivity by changing effective analyte hydrophobicity

Q13. In isothermal GC, lowering the oven temperature typically leads to which effect on resolution?

• Increased retention and potential selectivity enhancement, improving resolution but increasing run time
• Decreased retention and always improved resolution
• No effect on selectivity
• Increased detector noise without affecting resolution

Correct Answer: Increased retention and potential selectivity enhancement, improving resolution but increasing run time

Q14. For basic analytes on silica-based C18, increasing buffer concentration from 5 mM to 25 mM will most likely:

• Shield silanol interactions, reduce tailing, and improve resolution
• Increase mobile phase pH drastically
• Decrease system backpressure
• Degrade selectivity by ion-pairing with acidic species

Correct Answer: Shield silanol interactions, reduce tailing, and improve resolution

Q15. Injecting sample mass beyond the column’s linear capacity most commonly results in:

• Peak fronting or tailing and reduced resolution
• Sharper, symmetric peaks and improved resolution
• Increased number of theoretical plates
• Reduced backpressure and faster runs

Correct Answer: Peak fronting or tailing and reduced resolution

Q16. In capillary GC, increasing stationary-phase film thickness primarily:

• Increases retention of volatile analytes and can improve early-peak resolution
• Decreases retention of high boilers
• Eliminates the need for temperature programming
• Reduces selectivity for structural isomers

Correct Answer: Increases retention of volatile analytes and can improve early-peak resolution

Q17. For two nearly coeluting peaks (α = 1.03), which strategy provides the largest improvement in resolution for the same analysis time?

• Changing the mobile phase to increase α slightly
• Doubling the column length
• Increasing flow rate to reduce analysis time
• Increasing injection volume to boost signal

Correct Answer: Changing the mobile phase to increase α slightly

Q18. Under a fixed maximum pressure limit in UHPLC, which action can improve resolution without exceeding the pressure cap?

• Raise column temperature to lower solvent viscosity
• Increase flow rate at the same temperature
• Use smaller particles without other changes
• Install a longer column of the same particle size immediately

Correct Answer: Raise column temperature to lower solvent viscosity

Q19. Using a detector time constant or data rate that is too slow relative to peak width will:

• Broaden peaks and reduce apparent resolution
• Sharpen peaks but increase noise
• Have no effect on resolution
• Improve selectivity between closely eluting peaks

Correct Answer: Broaden peaks and reduce apparent resolution

Q20. In UV-Vis, to resolve two absorbance bands separated by ~1 nm, the most effective adjustment is to:

• Narrow the spectral bandwidth (slit width)
• Increase cuvette pathlength
• Raise detector voltage only
• Use a quartz cuvette instead of glass in the visible region

Correct Answer: Narrow the spectral bandwidth (slit width)

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