Nuclear magnetic resonance (NMR) spectroscopy is a cornerstone technique in pharmaceutical analysis for B. Pharm students. NMR aids structural elucidation, identification of impurities and metabolites, assessment of purity and polymorphism, and quantitative NMR (qNMR) for precise drug assay. Key approaches include proton NMR (1H NMR), carbon-13 NMR (13C NMR), and advanced two-dimensional experiments (COSY, HSQC, HMBC) for complex molecules. Applications cover formulation development, quality control, stability and degradation studies, and metabolite profiling. Mastery of chemical shifts, coupling constants, integration, relaxation effects and sample preparation is essential for reliable interpretation. These MCQs focus on practical NMR applications and interpretation skills. Now let’s test your knowledge with 30 MCQs on this topic.
Q1. What is the primary physical principle underlying NMR spectroscopy?
- Absorption of infrared radiation by molecular vibrations
- Interaction of nuclear magnetic moments with an external magnetic field
- Scattering of electrons by atomic nuclei
- Emission of photons after electronic excitation
Correct Answer: Interaction of nuclear magnetic moments with an external magnetic field
Q2. Which nucleus is most commonly observed in routine NMR for organic drug molecules?
- 31P
- 13C
- 1H
- 19F
Correct Answer: 1H
Q3. In 1H NMR, which parameter primarily indicates the electronic environment of a proton?
- Integration value
- Chemical shift (δ)
- Line width at half height
- Signal-to-noise ratio
Correct Answer: Chemical shift (δ)
Q4. The n+1 rule in proton NMR predicts multiplicity based on:
- The number of chemically equivalent neighboring protons
- The number of carbon atoms in the molecule
- The number of non-hydrogen heteroatoms
- The total molecular weight
Correct Answer: The number of chemically equivalent neighboring protons
Q5. Which deuterated solvent is most frequently used for 1H NMR of polar pharmaceutical compounds?
- CDCl3 (deuterated chloroform)
- DMSO-d6 (deuterated dimethyl sulfoxide)
- benzene-d6
- acetone-d6
Correct Answer: DMSO-d6 (deuterated dimethyl sulfoxide)
Q6. What is the role of tetramethylsilane (TMS) in NMR?
- Solvent for solid-state NMR
- Internal chemical shift reference at 0 ppm
- Relaxation agent to speed data acquisition
- Noise suppressor for low-concentration samples
Correct Answer: Internal chemical shift reference at 0 ppm
Q7. Which 2D NMR experiment is most useful for identifying direct one-bond 1H–13C correlations in drug molecules?
- COSY
- NOESY
- HSQC
- DEPT-135
Correct Answer: HSQC
Q8. DEPT experiments in 13C NMR primarily help to:
- Quantify low-concentration impurities
- Differentiate CH, CH2 and CH3 carbon types
- Measure molecular diffusion coefficients
- Detect exchangeable protons like OH and NH
Correct Answer: Differentiate CH, CH2 and CH3 carbon types
Q9. Quantitative NMR (qNMR) is favored for drug assay because it:
- Requires no reference standard
- Provides absolute quantification with an internal standard
- Is immune to relaxation effects
- Works only for aromatic compounds
Correct Answer: Provides absolute quantification with an internal standard
Q10. In qNMR, which factor is critical for accurate integration of peaks?
- Use of low magnetic field strength
- Appropriate relaxation delay to allow full relaxation
- Suppressing all solvent signals by presaturation
- Recording only one scan to avoid saturation
Correct Answer: Appropriate relaxation delay to allow full relaxation
Q11. Which NMR technique can help distinguish between different polymorphic forms of a solid drug?
- Solution 1H NMR
- Solid-state 13C CP/MAS NMR
- UV–Vis spectroscopy
- Gas chromatography
Correct Answer: Solid-state 13C CP/MAS NMR
Q12. Solvent suppression techniques in NMR are used to:
- Remove all signals below 1 ppm
- Reduce intense solvent peaks that obscure analyte signals
- Increase the natural abundance of 13C
- Calibrate the magnetic field homogeneity
Correct Answer: Reduce intense solvent peaks that obscure analyte signals
Q13. Which of the following best explains why 13C NMR requires more scans than 1H NMR?
- 13C has higher natural abundance than 1H
- 13C has a lower gyromagnetic ratio and lower natural abundance, leading to lower sensitivity
- 13C signals are intrinsically narrower and require averaging
- 13C nuclei relax instantaneously and need more scans to detect
Correct Answer: 13C has a lower gyromagnetic ratio and lower natural abundance, leading to lower sensitivity
Q14. Nuclear Overhauser Effect (NOE) experiments are primarily useful for:
- Determining direct one-bond heteronuclear couplings
- Studying spatial proximities and conformations
- Quantifying percent purity in formulations
- Measuring diffusion coefficients
Correct Answer: Studying spatial proximities and conformations
Q15. Which NMR parameter provides direct information about the number of equivalent protons in a signal?
- Chemical shift
- Integration (area under the peak)
- Coupling constant
- Line width
Correct Answer: Integration (area under the peak)
Q16. In the context of drug metabolite identification, which advantage does NMR offer over MS?
- Greater sensitivity for trace metabolites
- Direct structural information about connectivity and stereochemistry without fragmentation patterns
- Lower instrument cost
- Faster acquisition time for complex mixtures
Correct Answer: Direct structural information about connectivity and stereochemistry without fragmentation patterns
Q17. Which experiment helps correlate protons that are J-coupled to each other (through-bond proton–proton correlations)?
- COSY
- HSQC
- HMBC
- NOESY
Correct Answer: COSY
Q18. What effect does increasing temperature typically have on NMR spectra of a compound undergoing slow conformational exchange?
- Splitting of peaks into multiple unresolved components
- Coalescence of separate signals into averaged peaks as exchange rate increases
- Complete disappearance of all signals
- Increase in number of signals due to decomposition
Correct Answer: Coalescence of separate signals into averaged peaks as exchange rate increases
Q19. Which parameter is measured in DOSY NMR and is useful for distinguishing free drug from aggregates or excipient complexes?
- Chemical shift
- Diffusion coefficient
- Coupling constant
- Relaxation time T1
Correct Answer: Diffusion coefficient
Q20. For accurate detection of trace impurities by NMR, which strategy improves sensitivity most effectively?
- Reducing sample concentration
- Using a cryoprobe or higher-field magnet to increase sensitivity
- Shortening acquisition time dramatically
- Using non-deuterated solvents
Correct Answer: Using a cryoprobe or higher-field magnet to increase sensitivity
Q21. Which relaxation time is most relevant when choosing repetition delay for quantitative 1H NMR experiments?
- T2 (spin–spin relaxation time)
- T1 (spin–lattice relaxation time)
- T3 (spin–phonon relaxation time)
- NOE buildup time
Correct Answer: T1 (spin–lattice relaxation time)
Q22. In HMBC experiments, correlations are typically observed through how many bonds?
- One bond only
- Two to three bonds (commonly 2J and 3J heteronuclear correlations)
- Four to five bonds exclusively
- No bonds; HMBC measures spatial proximity
Correct Answer: Two to three bonds (commonly 2J and 3J heteronuclear correlations)
Q23. A broadened, weak NH signal that disappears on adding D2O indicates:
- The proton is part of an aliphatic CH3 group
- An exchangeable proton such as NH or OH
- A highly shielded aromatic proton
- Presence of paramagnetic impurities
Correct Answer: An exchangeable proton such as NH or OH
Q24. Which NMR observable is most directly used to determine stereochemistry about a double bond?
- Integration ratios
- Vicinal coupling constant (3JHH) between vinylic protons
- 13C chemical shift of methyl carbons
- Solvent residual peak position
Correct Answer: Vicinal coupling constant (3JHH) between vinylic protons
Q25. When selecting an internal standard for qNMR in drug analysis, the compound should be:
- Reactive with the analyte to form adducts
- Chemically inert, well-resolved from analyte peaks, and of known purity
- Present in trace amounts only
- Identical to the solvent used
Correct Answer: Chemically inert, well-resolved from analyte peaks, and of known purity
Q26. Heteronuclear decoupling during 13C acquisition is commonly used to:
- Introduce splitting from 1H–13C couplings
- Simplify the 13C spectrum by removing proton coupling and giving singlets
- Enhance solvent peaks only
- Measure diffusion rates
Correct Answer: Simplify the 13C spectrum by removing proton coupling and giving singlets
Q27. Which factor can cause unexpected downfield shifts (higher ppm) of protons in a drug molecule?
- Proximity to electron-donating groups only
- Deshielding by electronegative substituents or aromatic ring currents
- Use of deuterated solvent exclusively
- Lowering temperature always upfield
Correct Answer: Deshielding by electronegative substituents or aromatic ring currents
Q28. In impurity profiling by NMR, a practical advantage is that NMR can:
- Detect impurities only if they are volatile
- Provide structural identification of unknown impurities without prior separation
- Only quantify impurities above 50% abundance
- Replace the need for any chromatography
Correct Answer: Provide structural identification of unknown impurities without prior separation
Q29. Chiral shift reagents in NMR are used to:
- Increase signal-to-noise ratio for achiral compounds
- Differentiate enantiomers by inducing diastereomeric shifts
- Remove impurities selectively
- Convert 13C signals into 1H signals
Correct Answer: Differentiate enantiomers by inducing diastereomeric shifts
Q30. Which practice improves reproducibility of NMR-based stability studies for a drug formulation?
- Varying sample concentration between runs
- Standardizing sample preparation, temperature, solvent and acquisition parameters
- Using different internal standards for each time point
- Randomizing magnetic field strength for each analysis
Correct Answer: Standardizing sample preparation, temperature, solvent and acquisition parameters
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.
Mail- Sachin@pharmacyfreak.com