Analytical Method Validation MCQs With Answer

Introduction: Analytical Method Validation MCQs With Answer is designed for M.Pharm students specializing in Scale Up & Technology Transfer (MIP 202T). This collection covers critical principles of analytical method validation including ICH guidelines, system suitability, specificity, accuracy, precision, linearity, range, LOD/LOQ, robustness, forced degradation and method transfer considerations. Each question emphasizes practical aspects encountered during scale-up and technology transfer — for example establishing method equivalence between labs, designing validation protocols, and troubleshooting chromatographic issues. These MCQs aim to deepen conceptual understanding and prepare students for examinations and real-world pharmaceutical development tasks by reinforcing both regulatory expectations and analytical reasoning skills.

Q1. Which ICH guideline primarily defines the parameters and acceptance criteria for analytical method validation?

• ICH Q3A
• ICH Q2(R1)
• ICH Q8(R2)
• ICH Q1A(R2)

Correct Answer: ICH Q2(R1)

Q2. Which parameter is assessed by analysing replicate preparations from the same homogeneous sample on the same day under the same conditions?

• Intermediate precision
• Repeatability (intra-assay precision)
• Inter-laboratory precision
• Accuracy

Correct Answer: Repeatability (intra-assay precision)

Q3. What does the limit of quantitation (LOQ) represent in method validation?

• The lowest concentration that can be reliably detected but not quantified
• The lowest concentration that can be quantitatively determined with acceptable precision and accuracy
• The highest concentration within the linear range
• The concentration at which signal-to-noise ratio is 100

Correct Answer: The lowest concentration that can be quantitatively determined with acceptable precision and accuracy

Q4. In forced degradation studies, which demonstration is most important for calling a method ‘stability-indicating’?

• Ability to detect the active drug at a single pH
• Separation and detection of degradation products from the active peak
• High sensitivity for the active ingredient
• Reproducible retention time for the active peak only

Correct Answer: Separation and detection of degradation products from the active peak

Q5. Which statistical test is most appropriate for evaluating the linearity of a calibration curve where residuals may show heteroscedasticity?

• Unweighted least squares regression only
• Weighted least squares regression (e.g., 1/x or 1/x^2)
• Non-parametric Spearman correlation
• ANOVA without weighting

Correct Answer: Weighted least squares regression (e.g., 1/x or 1/x^2)

Q6. During a method transfer between an R&D lab and a manufacturing QC lab, what is the primary objective?

• To change the chromatographic column to a cheaper one
• To demonstrate the receiving lab can generate comparable data within predefined acceptance criteria
• To develop a completely new method for the receiving lab
• To validate the receiving lab’s equipment calibration only

Correct Answer: To demonstrate the receiving lab can generate comparable data within predefined acceptance criteria

Q7. Which system suitability parameter is used to assess column efficiency in HPLC?

• Tailor factor
• Theoretical plates (N)
• Resolution (Rs)
• Peak area reproducibility

Correct Answer: Theoretical plates (N)

Q8. When evaluating method robustness, which of the following is an appropriate experimental approach?

• Performing deliberate small changes to method parameters and observing effects
• Testing a single sample only under nominal conditions
• Changing major method components randomly without control
• Only changing sample concentration extremes

Correct Answer: Performing deliberate small changes to method parameters and observing effects

Q9. Which concept describes the closeness of agreement between the true value and the value found by the method?

• Precision
• Specificity
• Accuracy
• Linearity

Correct Answer: Accuracy

Q10. What is the main reason to perform method revalidation?

• Routine quarterly testing mandates
• Any significant change in method, equipment, or manufacturing process that can affect method performance
• To reduce the number of calibration points
• To change laboratory personnel

Correct Answer: Any significant change in method, equipment, or manufacturing process that can affect method performance

Q11. Which parameter helps to confirm that the method can selectively measure analyte in presence of excipients, impurities and degradation products?

• Linearity
• Specificity
• Precision
• Range

Correct Answer: Specificity

Q12. In an HPLC assay validation, a peak shows a tailing factor >2.0. Which of the following is the most likely consequence?

• Improved resolution between peaks
• Potential inaccurate integration and compromised quantitation
• Lower system backpressure
• Higher theoretical plate count

Correct Answer: Potential inaccurate integration and compromised quantitation

Q13. For determining method precision across different days and analysts, which term best describes this evaluation?

• Repeatability
• Intermediate precision (ruggedness)
• Specificity
• Accuracy

Correct Answer: Intermediate precision (ruggedness)

Q14. Which of the following is NOT typically included in a validation protocol?

• Acceptance criteria for each parameter
• Detailed experimental plan and sample matrix
• Vendor marketing brochure for reagents
• Number of replicates and statistical methods

Correct Answer: Vendor marketing brochure for reagents

Q15. Measurement uncertainty in analytical results is important because:

• It replaces the need for accuracy studies
• It quantifies the doubt about the result and supports decision-making for specification compliance
• It is only a regulatory formality with no practical use
• It indicates the limit of detection directly

Correct Answer: It quantifies the doubt about the result and supports decision-making for specification compliance

Q16. In validation of dissolution methods during scale-up, which factor is most critical to demonstrate?

• That dissolution apparatus is the cheapest available
• That dissolution method discriminates among batches and is reproducible across scales
• That the method gives the fastest release profile
• That the dissolution medium is always acidic

Correct Answer: That dissolution method discriminates among batches and is reproducible across scales

Q17. Which approach is appropriate to demonstrate equivalence when transferring a method to another lab using comparison of results?

• Qualitative agreement only
• Statistical comparison within predefined acceptance criteria (e.g., t-test, bias limits, percentage difference)
• Single sample measurement by both labs
• Comparing retention times without quantitative data

Correct Answer: Statistical comparison within predefined acceptance criteria (e.g., t-test, bias limits, percentage difference)

Q18. What is the primary purpose of a system suitability test before running a sample batch?

• To validate the method permanently
• To ensure the analytical system and method conditions are functioning properly for that run
• To calibrate the weighing balance
• To sterilize the HPLC column

Correct Answer: To ensure the analytical system and method conditions are functioning properly for that run

Q19. When calibration curve residuals display increasing variance at higher concentrations, which corrective action is recommended?

• Ignore the variance and use unweighted regression
• Use an appropriate weighting factor such as 1/x or 1/x^2 in regression
• Reduce the number of calibration points arbitrarily
• Switch to a single-point calibration

Correct Answer: Use an appropriate weighting factor such as 1/x or 1/x^2 in regression

Q20. Which experimental evidence best supports that a chromatographic method is rugged?

• Identical retention times on the same day using the same analyst
• Consistent assay results when method parameters, instruments, analysts or labs are varied within realistic ranges
• Only one calibration standard produces acceptable results
• Perfect peak symmetry regardless of mobile phase composition

Correct Answer: Consistent assay results when method parameters, instruments, analysts or labs are varied within realistic ranges

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