Analytical method validation – ICH & USP guidelines MCQs With Answer

Introduction

Analytical method validation – ICH & USP guidelines MCQs With Answer

This quiz set is designed for M.Pharm students to deepen understanding of analytical method validation as defined by ICH and USP. It focuses on core validation characteristics — accuracy, precision, specificity, linearity, range, LOD/LOQ, robustness, system suitability, forced degradation and method transfer — and connects those concepts to ICH Q2(R1) and USP chapters such as <1225> and <1226>. Questions emphasize practical application, statistical evaluation, and regulatory expectations so students can confidently design, assess and defend validated analytical procedures in pharmaceutical development and quality control.

Q1. Which ICH guideline specifically addresses the validation of analytical procedures?

• ICH Q1A(R2)
• ICH Q3A(R2)
• ICH Q2(R1)
• ICH Q7

Correct Answer: ICH Q2(R1)

Q2. Which USP chapter provides guidance on validation of compendial methods?

• <1058>
• <1225>
• <1226>
• <1220>

Correct Answer: <1225>

Q3. Which validation parameter describes the closeness of agreement between an accepted reference value and the value found?

• Precision
• Accuracy
• Specificity
• Robustness

Correct Answer: Accuracy

Q4. Which term describes precision assessed under a variety of conditions within the same laboratory (different days, analysts, equipment)?

• Repeatability
• Intermediate precision
• Reproducibility
• Ruggedness

Correct Answer: Intermediate precision

Q5. According to ICH Q2(R1), which formula is used to estimate the limit of quantitation (LOQ) from the calibration curve?

• LOQ = 3.3 × σ / S
• LOQ = 10 × σ / S
• LOQ = 1.96 × σ / S
• LOQ = σ / S

Correct Answer: LOQ = 10 × σ / S

Q6. Which validation characteristic is defined as the ability to measure the analyte unequivocally in the presence of components which may be expected to be present?

• Linearity
• Specificity
• Accuracy
• Precision

Correct Answer: Specificity

Q7. How is the ‘range’ of an analytical method best described?

• The interval between the highest and lowest response units observed
• The interval between concentrations where the method has acceptable accuracy, precision and linearity
• The interval between LOD and double the LOQ
• The interval where the calibration curve has a slope equal to one

Correct Answer: The interval between concentrations where the method has acceptable accuracy, precision and linearity

Q8. Which statistical indicator is commonly used to evaluate linearity of an analytical method?

• Relative standard deviation (RSD)
• Correlation coefficient (r or r²)
• Grubbs’ statistic
• F-test for variances

Correct Answer: Correlation coefficient (r or r²)

Q9. What is the primary purpose of system suitability tests before running analytical samples?

• To validate the entire method permanently
• To verify system performance (e.g., resolution, tailing, theoretical plates, precision) prior to analysis
• To calculate LOD and LOQ
• To determine the purity of reference standard

Correct Answer: To verify system performance (e.g., resolution, tailing, theoretical plates, precision) prior to analysis

Q10. Which definition best fits ‘robustness’ in method validation?

• The degree to which an analytical method yields the same result on different days
• The ability to remain unaffected by small, deliberate variations in method parameters and provides an indication of its reliability
• The closeness of measured value to true value
• The slope of calibration curve

Correct Answer: The ability to remain unaffected by small, deliberate variations in method parameters and provides an indication of its reliability

Q11. What is the main objective of forced degradation studies when developing a stability-indicating method?

• To accelerate the production process
• To generate degradation products to demonstrate the method can separate and detect them from the active analyte
• To improve the sensitivity of the method
• To increase the signal-to-noise ratio

Correct Answer: To generate degradation products to demonstrate the method can separate and detect them from the active analyte

Q12. Which statistical test is commonly used to detect a single outlier in a small dataset during validation studies?

• Student’s t-test
• ANOVA
• Grubbs’ test
• Chi-square test

Correct Answer: Grubbs’ test

Q13. Which experimental approach is commonly used to assess accuracy via recovery in the presence of matrix effects?

• Standard addition (spike recovery)
• External standard calibration without spikes
• Blank subtraction only
• Use of an unvalidated internal standard

Correct Answer: Standard addition (spike recovery)

Q14. For impurity methods, which validation attribute is especially critical to ensure regulatory compliance?

• Speed of analysis
• Sensitivity (LOD/LOQ) sufficient to detect/report impurities at the reporting threshold
• Cost of solvents
• Peak symmetry only

Correct Answer: Sensitivity (LOD/LOQ) sufficient to detect/report impurities at the reporting threshold

Q15. Which term refers to method performance reproducibility demonstrated between different laboratories?

• Repeatability
• Intermediate precision
• Reproducibility
• Robustness

Correct Answer: Reproducibility

Q16. When is weighting (e.g., 1/x or 1/x²) applied during calibration curve regression?

• When homoscedasticity is present across concentrations
• When heteroscedasticity is observed and variance changes with concentration
• Only when using internal standards
• To force the intercept to zero

Correct Answer: When heteroscedasticity is observed and variance changes with concentration

Q17. Which USP chapter provides guidance specifically on verification of compendial procedures (method transfer and verification)?

• <1225>
• <1226>
• <1058>
• <1010>

Correct Answer: <1226>

Q18. Which of the following contributes to measurement uncertainty in an analytical result?

• Uncertainty of calibration standards
• Instrument repeatability and method bias
• Sample preparation variability and environmental factors
• All of the above

Correct Answer: All of the above

Q19. Which parameter is NOT typically part of system suitability criteria evaluated before sample analysis?

• Number of theoretical plates
• Resolution between critical peaks
• Signal-to-noise ratio of the blank
• Calibration curve linearity across the full analytical range

Correct Answer: Calibration curve linearity across the full analytical range

Q20. What is the main requirement when transferring an analytical method from a development lab to a quality control laboratory?

• The receiving laboratory must re-develop the entire method
• The receiving laboratory must demonstrate it can perform the method by verification of key performance characteristics (e.g., system suitability, precision, accuracy)
• Only the equipment needs to be documented
• No action is required if SOPs are available

Correct Answer: The receiving laboratory must demonstrate it can perform the method by verification of key performance characteristics (e.g., system suitability, precision, accuracy)

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