Derivatization in GC MCQs With Answer

Derivatization in GC MCQs With Answer is a focused quiz resource tailored for M.Pharm students studying Advanced Instrumental Analysis (MPA 201T). This collection emphasizes practical and conceptual aspects of chemical derivatization used to make non-volatile or thermally labile pharmaceutical analytes amenable to gas chromatography. Questions cover reagents, mechanisms, reaction conditions, analytical benefits (volatility, stability, detectability), common pitfalls, on-line vs off-line strategies, safety concerns and interpretation in GC and GC–MS. Designed to reinforce classroom learning and exam preparation, the set balances fundamental theory with application-based scenarios that reflect real laboratory considerations in pharmaceutical analysis.

Q1. What is the primary analytical purpose of chemical derivatization in gas chromatography?

• To increase analyte volatility and thermal stability for GC analysis
• To decrease analyte molecular weight so it elutes faster
• To permanently bind analytes to the stationary phase
• To convert all analytes into charged species for GC separation

Correct Answer: To increase analyte volatility and thermal stability for GC analysis

Q2. Which general derivatization strategy is most commonly used to modify hydroxyls, carboxyls and amines for GC?

• Silylation (formation of trimethylsilyl or other silyl derivatives)
• Oxidation to carbonyls
• Hydrogenation to reduce polarity
• Complexation with crown ethers

Correct Answer: Silylation (formation of trimethylsilyl or other silyl derivatives)

Q3. N,O-bis(trimethylsilyl)trifluoroacetamide is the chemical name for which commonly used silylation reagent?

• BSTFA
• MSTFA
• MTBSTFA
• PFPA

Correct Answer: BSTFA

Q4. Which reagent is specifically used to introduce the tert-butyldimethylsilyl (TBDMS) protecting group for increased derivative stability?

• MTBSTFA (N-tert-butyldimethylsilyl-N-methyltrifluoroacetamide)
• BSTFA
• Diazomethane
• PFBBr (pentafluorobenzyl bromide)

Correct Answer: MTBSTFA (N-tert-butyldimethylsilyl-N-methyltrifluoroacetamide)

Q5. Which reagent is most commonly used to methylate carboxylic acids to form methyl esters for GC analysis, but requires extreme safety precautions?

• Diazomethane
• BSTFA
• Pyridine
• PFPA

Correct Answer: Diazomethane

Q6. Mechanistically, silylation of an alcohol involves which key step?

• Nucleophilic attack of the oxygen on silicon, displacing a leaving group to form a Si–O bond
• Free radical abstraction of hydrogen to form a radical intermediate
• Hydrogen transfer to the reagent followed by elimination of water
• Formation of a coordination complex without covalent bond formation

Correct Answer: Nucleophilic attack of the oxygen on silicon, displacing a leaving group to form a Si–O bond

Q7. How does derivatization commonly improve GC–MS detection of polar analytes?

• By producing more volatile and thermally stable derivatives with characteristic fragmentation patterns in EI-MS
• By converting analytes into non-ionizable neutral species to avoid MS suppression
• By significantly increasing molecular weight to prevent fragmentation
• By binding analytes irreversibly to ionization sources

Correct Answer: By producing more volatile and thermally stable derivatives with characteristic fragmentation patterns in EI-MS

Q8. Which statement best describes silylation reagents like BSTFA or MSTFA regarding moisture?

• They are highly moisture-sensitive and are hydrolyzed by water, reducing derivatization efficiency
• They are inert to water and perform equally well in aqueous solutions
• They require water to activate the silyl group for reaction
• They form stable hydrates that improve GC peak shape

Correct Answer: They are highly moisture-sensitive and are hydrolyzed by water, reducing derivatization efficiency

Q9. Which solvent often acts both as reaction medium and acid–base catalyst for silylation reactions?

• Pyridine
• Hexane
• Water
• Methanol

Correct Answer: Pyridine

Q10. Which derivatization reagent is commonly used to introduce an electron-capturing pentafluorobenzyl (PFB) group to enhance detection by electron capture or negative-ion MS?

• PFBBr (pentafluorobenzyl bromide)
• BSTFA
• Diazomethane
• Imidazole

Correct Answer: PFBBr (pentafluorobenzyl bromide)

Q11. What is a primary advantage of on-line (injection port) derivatization compared with off-line derivatization?

• Greater automation with reduced manual handling and lower contamination risk
• Ability to use larger reaction volumes for higher yield
• Long reaction times without effect on throughput
• Complete elimination of reagent side-products

Correct Answer: Greater automation with reduced manual handling and lower contamination risk

Q12. Which classes of pharmaceutical analytes typically require derivatization before GC analysis?

• Polar and thermally labile compounds such as alcohols, carboxylic acids, amines, sugars and phenols
• All small non-polar hydrocarbons
• Only inorganic salts and metal complexes
• Proteins and large polypeptides without prior hydrolysis

Correct Answer: Polar and thermally labile compounds such as alcohols, carboxylic acids, amines, sugars and phenols

Q13. In quantitative GC, incomplete derivatization most commonly results in what analytical problem?

• Underestimation of analyte concentration due to mixture of derivatized and underivatized species
• False increase in analyte concentration due to reagent contamination
• Complete loss of chromatographic resolution of all peaks
• Transformation of analytes into the same single peak

Correct Answer: Underestimation of analyte concentration due to mixture of derivatized and underivatized species

Q14. Which nucleophilic catalyst is commonly used to accelerate silylation reactions?

• Imidazole
• Sulfuric acid
• Hydrochloric acid
• Sodium chloride

Correct Answer: Imidazole

Q15. For sterically hindered or more stable silyl derivatives that resist hydrolysis, which reagent is preferred?

• MTBSTFA (gives tert-butyldimethylsilyl derivatives)
• BSTFA (gives trimethylsilyl derivatives)
• PFBBr
• Acetic anhydride

Correct Answer: MTBSTFA (gives tert-butyldimethylsilyl derivatives)

Q16. Which detector is particularly enhanced by perfluoroacylation or pentafluorobenzylation of analytes?

• Electron capture detector (ECD) / negative-ion MS (ECNI)
• Flame ionization detector (FID) only
• Thermal conductivity detector (TCD) exclusively
• Refractive index detector

Correct Answer: Electron capture detector (ECD) / negative-ion MS (ECNI)

Q17. What common chromatographic artifact may indicate incomplete or competing derivatization reactions?

• Multiple peaks for a single analyte corresponding to underivatized, partially-derivatized and fully-derivatized species
• Single, sharp peak with unusually high intensity
• Total suppression of all analyte signals only
• Complete co-elution of solvent with all analytes

Correct Answer: Multiple peaks for a single analyte corresponding to underivatized, partially-derivatized and fully-derivatized species

Q18. Which reagent is commonly used to quench residual silylation reagent after the reaction is complete?

• Methanol (to hydrolyze excess silylating agent)
• Sulfuric acid (to protonate the derivatives)
• Hexane (to precipitate reagents)
• Pyridine (to further catalyze the reaction)

Correct Answer: Methanol (to hydrolyze excess silylating agent)

Q19. Typical reaction conditions to achieve complete silylation with reagents like MSTFA or BSTFA are often:

• Moderate heating (e.g., 60–80 °C) for tens of minutes to an hour
• Cryogenic temperatures to stabilize reactive intermediates
• Very high temperatures above 200 °C for rapid conversion
• Strictly anaerobic conditions at room temperature for days

Correct Answer: Moderate heating (e.g., 60–80 °C) for tens of minutes to an hour

Q20. Which of the following safety statements about diazomethane is correct?

• Diazomethane is toxic, potentially explosive and must be generated and handled with strict precautions in a fume hood
• Diazomethane is non-toxic and safe to use on open bench with no precautions
• Diazomethane decomposes into harmless gases at room temperature and does not require special disposal
• Diazomethane is a mild acid used to catalyze silylation reactions

Correct Answer: Diazomethane is toxic, potentially explosive and must be generated and handled with strict precautions in a fume hood

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