Applications of IR spectroscopy in drug analysis MCQs With Answer

Introduction: Infrared (IR) spectroscopy is a core analytical technique in pharmaceutical analysis, essential for B.Pharm students studying drug identification, structural elucidation and quality control. IR (including FTIR and ATR) detects molecular vibrational modes and characteristic functional group absorptions—such as carbonyl (~1700 cm−1), O–H, N–H and C≡N—allowing fingerprint matching, polymorph differentiation, impurity profiling and salt form identification. Practical skills include sample preparation (KBr pellet, Nujol mull, ATR), spectra interpretation, understanding fingerprint region and troubleshooting band shifts from hydrogen bonding or conjugation. Mastery of IR applications supports stability studies, formulation testing and regulatory documentation. Now let’s test your knowledge with 30 MCQs on this topic.

Q1. What is the primary physical property measured by IR spectroscopy?

  • Electronic transitions in molecules
  • Molecular vibrational transitions measured as absorbance in wavenumbers (cm−1)
  • Mass-to-charge ratio of ionized fragments
  • Nuclear spin transitions in a magnetic field

Correct Answer: Molecular vibrational transitions measured as absorbance in wavenumbers (cm−1)

Q2. Which region of an IR spectrum is known as the fingerprint region?

  • 4000–3000 cm−1
  • 3000–2000 cm−1
  • 2000–1500 cm−1
  • Below 1500 cm−1

Correct Answer: Below 1500 cm−1

Q3. A strong, sharp peak near 1700 cm−1 typically indicates which functional group?

  • Alcohol (O–H)
  • Carbonyl (C=O)
  • Alkene (C=C)
  • Nitro (NO2)

Correct Answer: Carbonyl (C=O)

Q4. Which sample preparation technique is best for direct analysis of solid tablets with minimal sample destruction?

  • KBr pellet
  • ATR (attenuated total reflectance)
  • Nujol mull
  • Gas-phase cell

Correct Answer: ATR (attenuated total reflectance)

Q5. Hydrogen bonding typically causes which change in an O–H stretching band?

  • Shift to higher wavenumber and sharpening
  • Shift to lower wavenumber and broadening
  • No change in position but increased intensity
  • Disappearance of the band

Correct Answer: Shift to lower wavenumber and broadening

Q6. Which advantage is specifically associated with FTIR over dispersive IR?

  • Slower scan speed
  • Lower signal-to-noise ratio
  • Multiplex (Fellgett) advantage yielding faster scans and better S/N
  • Only usable for gases

Correct Answer: Multiplex (Fellgett) advantage yielding faster scans and better S/N

Q7. Which functional group gives a sharp, strong absorption near 2100–2260 cm−1?

  • Alcohol (O–H)
  • Nitrile (C≡N)
  • Carbonyl (C=O)
  • Aromatic C–H

Correct Answer: Nitrile (C≡N)

Q8. In pharmaceutical quality control, IR is most commonly used for which purpose?

  • Determining exact molecular mass
  • Quantitative trace metal analysis
  • Identification and confirmation of API and excipients
  • Measuring tablet hardness

Correct Answer: Identification and confirmation of API and excipients

Q9. Why is the fingerprint region valuable for drug identification?

  • It shows only broad O–H absorptions
  • It is highly unique to a molecule’s entire structural framework
  • It gives mass information of fragments
  • It is unaffected by sample preparation

Correct Answer: It is highly unique to a molecule’s entire structural framework

Q10. Which sampling technique uses mineral oil to suspend a solid sample for IR analysis?

  • KBr pellet method
  • Nujol mull
  • ATR
  • Diffuse reflectance (DRIFTS)

Correct Answer: Nujol mull

Q11. How does conjugation affect the C=O stretching frequency?

  • Conjugation usually increases the frequency
  • Conjugation usually decreases the frequency
  • Conjugation eliminates the C=O band
  • Conjugation converts C=O to C–O absorption

Correct Answer: Conjugation usually decreases the frequency

Q12. Which limitation applies to IR spectroscopy when analyzing drug impurities at trace levels?

  • IR is inherently element-specific
  • IR often lacks sensitivity for trace-level detection without enrichment
  • IR can readily quantify parts-per-billion impurities without calibration
  • IR produces no fingerprint information

Correct Answer: IR often lacks sensitivity for trace-level detection without enrichment

Q13. ATR-FTIR mainly measures which property of the sample?

  • Bulk transmission through thick slabs
  • Surface or near-surface absorption via evanescent wave interaction
  • Gas-phase rotational transitions
  • Magnetic resonance signals

Correct Answer: Surface or near-surface absorption via evanescent wave interaction

Q14. Which spectral change indicates protonation of an amine in a drug molecule?

  • Disappearance of all N–H bands
  • Shift and possible broadening of N–H and related bands due to salt formation
  • Appearance of a new C=C band at 1600 cm−1
  • Complete loss of fingerprint region features

Correct Answer: Shift and possible broadening of N–H and related bands due to salt formation

Q15. For quantitative IR analysis of an API, which practice is essential?

  • Using a mass spectrometer alongside
  • Establishing a calibration curve and controlling sample preparation
  • Only recording a single spectrum without standards
  • Measuring in the ultraviolet range

Correct Answer: Establishing a calibration curve and controlling sample preparation

Q16. Which band change is commonly used to detect ester hydrolysis in stability studies?

  • Increase in C=O ester band intensity at 1740 cm−1 without any other changes
  • Disappearance or shift of the ester C=O and appearance of carboxylic acid O–H and C=O bands
  • Appearance of strong nitrile band at 2250 cm−1
  • Loss of all C–H stretching bands above 3000 cm−1

Correct Answer: Disappearance or shift of the ester C=O and appearance of carboxylic acid O–H and C=O bands

Q17. Which instrumental component splits and disperses IR radiation in a dispersive spectrometer?

  • Interferometer
  • Diffraction grating
  • Mass analyzer
  • Polarizer

Correct Answer: Diffraction grating

Q18. Which statement about transmittance vs absorbance in IR spectra is correct?

  • Transmittance increases when absorbance increases
  • Absorbance is the negative logarithm of transmittance
  • They are unrelated scales
  • IR instruments only report absorbance not transmittance

Correct Answer: Absorbance is the negative logarithm of transmittance

Q19. Which IR technique is most suitable for powdered samples without pellet formation?

  • Gas-phase IR
  • ATR-FTIR or DRIFTS
  • Liquid cell transmission only
  • UV-Vis spectroscopy

Correct Answer: ATR-FTIR or DRIFTS

Q20. Which of the following cannot be detected by IR spectroscopy?

  • Hydrogen-bonded O–H stretching
  • Homonuclear diatomic molecules like N2 or O2 in their ground state
  • Carbonyl functional groups
  • Nitrile groups

Correct Answer: Homonuclear diatomic molecules like N2 or O2 in their ground state

Q21. How can IR help distinguish between polymorphic forms of a drug?

  • Polymorphs show identical IR spectra always
  • Polymorphs can show small shifts or intensity changes in characteristic bands due to different intermolecular interactions
  • Polymorphs are only distinguishable by mass spectrometry
  • Polymorphs alter atomic number making IR useless

Correct Answer: Polymorphs can show small shifts or intensity changes in characteristic bands due to different intermolecular interactions

Q22. Which factor most commonly causes band broadening in an IR spectrum of a pharmaceutical sample?

  • Instrument having too high resolution
  • Hydrogen bonding and sample heterogeneity
  • Perfect crystalline order
  • Low sample concentration always sharpens bands

Correct Answer: Hydrogen bonding and sample heterogeneity

Q23. In ATR-FTIR, penetration depth of the evanescent wave depends primarily on which parameter?

  • Sample pH only
  • Refractive indices of crystal and sample and wavelength
  • Mass of the sample
  • Magnetic susceptibility

Correct Answer: Refractive indices of crystal and sample and wavelength

Q24. Which absorption is diagnostic for aromatic rings in IR spectra?

  • Sharp strong band at 1700 cm−1 only
  • Multiple bands in 1600–1450 cm−1 region and C–H out-of-plane bends 900–650 cm−1
  • Single band at 2250 cm−1
  • No bands appear for aromatics

Correct Answer: Multiple bands in 1600–1450 cm−1 region and C–H out-of-plane bends 900–650 cm−1

Q25. When matching an unknown drug spectrum to a reference, which practice improves confidence?

  • Matching only one characteristic peak
  • Comparing multiple characteristic peaks including fingerprint region and sample-handling consistency
  • Using only peak intensity without wavenumber checks
  • Ignoring sample form differences (salt vs free base)

Correct Answer: Comparing multiple characteristic peaks including fingerprint region and sample-handling consistency

Q26. What effect does salt formation typically have on an acid or base drug IR spectrum?

  • No observable effect
  • Shifts in acid or base related bands and changes in intensity due to ionic interactions
  • Creates peaks only above 4000 cm−1
  • Eliminates the fingerprint region entirely

Correct Answer: Shifts in acid or base related bands and changes in intensity due to ionic interactions

Q27. Which IR method is useful for analyzing coatings or thin films on tablets?

  • Transmission through thick pellet only
  • ATR-FTIR with appropriate contact or micro-ATR accessories
  • Gas chromatography
  • Atomic absorption spectroscopy

Correct Answer: ATR-FTIR with appropriate contact or micro-ATR accessories

Q28. Which band is characteristic of primary amines in the 3300–3500 cm−1 region?

  • Single sharp O–H band
  • Two N–H stretching bands often appearing as two peaks
  • Strong carbonyl band
  • No bands in this region for amines

Correct Answer: Two N–H stretching bands often appearing as two peaks

Q29. For IR spectral interpretation, which complementary technique often helps confirm functional group assignments?

  • Mass spectrometry (MS) and NMR spectroscopy
  • Colorimetry only
  • Thermal gravimetric analysis alone
  • Polarimetry only

Correct Answer: Mass spectrometry (MS) and NMR spectroscopy

Q30. What is a common reason for baseline drift or noise in an IR spectrum of a tablet?

  • Perfect instrument alignment
  • Inadequate background correction, atmospheric water/CO2, or poor contact in ATR
  • Using KBr pellet correctly
  • Presence of only pure API with no excipients

Correct Answer: Inadequate background correction, atmospheric water/CO2, or poor contact in ATR

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