Novel sample preparation approaches MCQs With Answer
Introduction
This quiz set focuses on novel sample preparation approaches used in modern bio-analytical techniques, tailored for M.Pharm students. It covers advanced extraction and clean-up methods such as solid-phase microextraction, QuEChERS, dispersive SPE, microfluidic sampling, dried blood spots, and ambient ionization techniques. Questions explore principles, sorbent materials, automation, green chemistry benefits, method optimization, and common pitfalls in translating these approaches to regulated bioanalysis. The aim is to deepen conceptual understanding and practical application so students can select and optimize appropriate sample preparation strategies for complex biological matrices in research and regulated environments.
Q1. Which principle best describes Solid-Phase Microextraction (SPME)?
- Partitioning of analytes between a sorbent-coated fiber and the sample matrix
- Centrifugal separation based on density differences
- Direct thermal desorption of the sample without sorbent
- Liquid-liquid extraction using immiscible solvents
Correct Answer: Partitioning of analytes between a sorbent-coated fiber and the sample matrix
Q2. What is the primary advantage of QuEChERS for pesticide residue analysis in complex matrices?
- High solvent consumption and long extraction times
- Fast, low-cost extraction with effective clean-up using dispersive SPE
- Exclusive suitability for volatile analytes only
- Requirement of specialized high-pressure equipment
Correct Answer: Fast, low-cost extraction with effective clean-up using dispersive SPE
Q3. In dispersive solid-phase extraction (dSPE), what role does the sorbent play?
- It acts as a reactive catalyst to modify analytes chemically
- It selectively retains matrix interferences while allowing analytes to remain in solution
- It increases sample volume by swelling in solvent
- It evaporates to concentrate analytes
Correct Answer: It selectively retains matrix interferences while allowing analytes to remain in solution
Q4. Which statement best describes Dried Blood Spot (DBS) sampling benefits?
- Requires large blood volumes and immediate refrigeration
- Enables minimal invasiveness, small sample volume, and convenient transport
- Always eliminates hematocrit effects without further consideration
- Is incompatible with LC-MS/MS analysis
Correct Answer: Enables minimal invasiveness, small sample volume, and convenient transport
Q5. Which of the following is a key limitation of conventional liquid-liquid extraction (LLE) compared to microextraction techniques?
- Low solvent usage and fully automated workflows
- High selectivity for polar analytes without modifiers
- Large solvent consumption and emulsification issues
- Inability to extract neutral compounds
Correct Answer: Large solvent consumption and emulsification issues
Q6. Stir-Bar Sorptive Extraction (SBSE) differs from SPME primarily by:
- Using a larger sorbent phase coated on a stir bar allowing higher capacity
- Requiring direct immersion into GC without desorption
- Being limited to gas-phase sampling only
- Not being compatible with thermal desorption techniques
Correct Answer: Using a larger sorbent phase coated on a stir bar allowing higher capacity
Q7. Pressurized Liquid Extraction (PLE) (also known as ASE) enhances extraction efficiency by:
- Using elevated temperature and pressure to increase analyte solubility and diffusion
- Freezing the matrix to cause phase separation
- Employing enzymatic digestion to release bound analytes
- Adding ionic liquids as the only extracting solvents
Correct Answer: Using elevated temperature and pressure to increase analyte solubility and diffusion
Q8. Which sorbent is commonly used for trapping polar acidic analytes in mixed-mode SPE?
- Reverse-phase C18 only
- Anion-exchange sorbent
- Graphitized carbon black exclusively
- Hydrophobic polydimethylsiloxane without functional groups
Correct Answer: Anion-exchange sorbent
Q9. Paper Spray Ionization is best described as:
- A chromatographic separation technique prior to MS
- An ambient ionization method where sample on paper is ionized by solvent and high voltage for direct MS analysis
- A form of headspace extraction for VOCs only
- Identical to electrospray but requires capillaries
Correct Answer: An ambient ionization method where sample on paper is ionized by solvent and high voltage for direct MS analysis
Q10. Which parameter is most critical to control during microextraction to ensure reproducible partitioning?
- Sample color
- Temperature and ionic strength of the sample matrix
- Manufacturer of the extraction vial
- Ambient light intensity
Correct Answer: Temperature and ionic strength of the sample matrix
Q11. Matrix Solid-Phase Dispersion (MSPD) is particularly useful for:
- Analyzing gaseous pollutants directly from air
- Simultaneous disruption of a solid matrix and extraction/clean-up using a sorbent blended with the sample
- Only liquid matrices with no particulate matter
- High-pressure separation of proteins
Correct Answer: Simultaneous disruption of a solid matrix and extraction/clean-up using a sorbent blended with the sample
Q12. Which of the following describes the main green chemistry benefit of microextraction techniques?
- Increased use of chlorinated solvents
- Significant reduction in organic solvent consumption and waste generation
- Requirement for toxic sorbent regeneration chemicals
- Longer energy-intensive procedures
Correct Answer: Significant reduction in organic solvent consumption and waste generation
Q13. Solid-phase enhanced sample preparation (SPESP) commonly aims to:
- Combine extraction and selective enrichment to improve sensitivity and throughput
- Replace mass spectrometry with spectrophotometry
- Dilute samples to reduce matrix effects
- Eliminate the need for calibration standards
Correct Answer: Combine extraction and selective enrichment to improve sensitivity and throughput
Q14. Which miniaturized approach is most suitable for on-site rapid screening of drugs in biological fluids?
- Traditional Soxhlet extraction
- Paper spray MS and portable ambient ionization techniques
- Large-scale liquid-liquid extraction requiring fume hoods
- High-volume pressurized hot-water extraction
Correct Answer: Paper spray MS and portable ambient ionization techniques
Q15. When optimizing QuEChERS clean-up, which sorbent is typically added to remove lipids?
- Primary-secondary amine (PSA) only
- C18 or zirconia-based sorbents like Z-Sep
- Silica gel to retain small polar molecules exclusively
- Activated carbon to retain volatile acids
Correct Answer: C18 or zirconia-based sorbents like Z-Sep
Q16. Which analytical challenge is specifically addressed by on-line SPE coupled with LC-MS/MS?
- Elimination of the need for mass spectrometers
- Automation of sample clean-up and direct transfer to chromatographic system to increase throughput and reproducibility
- Requirement for larger sample volumes relative to batch SPE
- Replacement of chromatographic separation entirely
Correct Answer: Automation of sample clean-up and direct transfer to chromatographic system to increase throughput and reproducibility
Q17. What is the primary concern when using Dried Matrix Spots (DMS) for quantitative bioanalysis?
- Complete elimination of analyte instability
- Impact of hematocrit and spot homogeneity on quantitative recovery
- Excessive solvent use during sampling
- Incompatibility with LC-based methods
Correct Answer: Impact of hematocrit and spot homogeneity on quantitative recovery
Q18. Which microextraction technique relies on a thin immiscible solvent film supported on a porous membrane for extraction?
- Supported Liquid Membrane Extraction (SLME)
- Conventional LLE without support
- Soxhlet extraction
- Solid-phase microextraction with polymeric fiber only
Correct Answer: Supported Liquid Membrane Extraction (SLME)
Q19. Ambient ionization techniques (e.g., DESI, DART) are advantageous because they:
- Require extensive chromatographic separation prior to MS
- Allow direct analysis of samples with minimal or no sample preparation
- Are limited to ultraviolet detection only
- Always provide higher quantitative precision than LC-MS/MS
Correct Answer: Allow direct analysis of samples with minimal or no sample preparation
Q20. In method validation for novel sample preparation, which parameter must be rigorously evaluated to ensure suitability for regulatory bioanalysis?
- Only the visual appearance of extracts
- Recovery, matrix effects, precision, accuracy, and stability under expected conditions
- Manufacturer brand of sorbents used exclusively
- Sample color after extraction as the sole criterion
Correct Answer: Recovery, matrix effects, precision, accuracy, and stability under expected conditions

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.
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