uniquely identify the analyte in the presence of excipients, impurities, or other components.

2. Scope

This procedure applies to FTIR-based analytical methods in the Analytical Method Development (AMD) laboratory. It covers the comparison of API spectra against blanks, placebos, excipients, and reference standards for confirming unique identification.

3. Responsibilities

• Analytical Chemist: Performs the sample and placebo spectrum acquisition and overlays.
• Reviewer: Reviews spectral overlays, matches functional peaks, and evaluates interference.
• QA Officer: Ensures compliance with ICH guidelines and verifies data integrity.
• Head – AMD: Approves specificity validation results and method suitability.

4. Accountability

The Head of Analytical Method Development is accountable for confirming the specificity of FTIR methods used for product identification and ensuring results are scientifically and regulatory compliant.

5. Procedure

5.1 Sample Preparation

1. Prepare samples using KBr pellet or ATR method as per SOP/AMD/096 and SOP/AMD/097 respectively.
2. Ensure uniformity of samples and complete drying to eliminate spectral distortion.
3. Prepare blank (KBr only or clean ATR), placebo (excipients only), and standard/reference sample for comparative scanning.
4. Record preparation details in Annexure-1: Sample Preparation Log.

5.2 Background and Blank Spectrum

1. Run background spectrum using clean KBr or ATR crystal as applicable.
2. Ensure no significant absorbance in the functional group region (4000–1800 cm^-1) or fingerprint region (1800–600 cm^-1).
3. Scan and document blank in Annexure-2: Blank Spectrum Log.

5.3 Placebo and Excipients Spectrum

1. Scan excipient-only placebo using the same method used for API.
2. Compare its spectrum with API to identify potential overlapping peaks or interferences.
3. Acceptable if placebo does not contain peaks in critical fingerprint region or API signature peaks.
4. Document in Annexure-3: Placebo Spectrum Sheet.

5.4 Test Sample and Reference Spectrum

1. Scan API test sample and official reference standard under identical parameters.
2. Evaluate peak alignment, intensity, and overall shape across the entire spectrum.
3. Overlay the test spectrum with standard to verify match percentage (target ≥ 95%).
4. Accept if API spectrum is distinguishable from placebo and matches reference.
5. Document in Annexure-4: Specificity Evaluation Sheet.

5.5 Peak Interpretation and Match Criteria

1. Focus on fingerprint region: 1800–600 cm^-1.
2. Evaluate the following:
   • Peak positions ±5 cm^-1 from reference
   • No significant peaks in placebo spectrum at same wavenumbers
   • Relative peak intensity within ±10%
3. Document and comment on match quality in Annexure-5: Spectral Match Commentary.

5.6 Reporting Specificity

1. Specificity is confirmed when:
   • The analyte can be uniquely identified in the presence of other components.
   • Overlay with reference standard shows ≥ 95% match.
   • Placebo spectra do not interfere with major analytical peaks.
2. Generate a final report and obtain approval from department head and QA.

6. Abbreviations

• FTIR: Fourier Transform Infrared
• ATR: Attenuated Total Reflectance
• API: Active Pharmaceutical Ingredient
• SOP: Standard Operating Procedure
• cm^-1: Wavenumber

7. Documents

1. Sample Preparation Log – Annexure-1
2. Blank Spectrum Log – Annexure-2
3. Placebo Spectrum Sheet – Annexure-3
4. Specificity Evaluation Sheet – Annexure-4
5. Spectral Match Commentary – Annexure-5

8. References

• ICH Q2(R1) – Validation of Analytical Procedures
• USP <197K> – FTIR Identification Tests
• Internal FTIR Method SOPs

9. SOP Version

Version: 2.0

10. Approval Section

	Prepared By	Checked By	Approved By
Signature
Date
Name
Designation
Department

11. Annexures

Annexure-1: Sample Preparation Log

ID	Sample Type	Method Used	Operator
SPEC-099	API	ATR	Rajesh Kumar
SPEC-099-PL	Placebo	KBr	Sunita Reddy

Annexure-2: Blank Spectrum Log

Date	Type	Scan Range	Result
19/05/2025	ATR Blank	4000–400 cm-1	No Interference

Annexure-3: Placebo Spectrum Sheet

Peak (cm-1)	Intensity	Overlaps with API?
3450	Weak	No
1700	None	No

Annexure-4: Specificity Evaluation Sheet

Sample vs Standard	Overlay Match (%)	Status
SPEC-099 vs REF-STD	96.4%	Pass

Annexure-5: Spectral Match Commentary

Wavenumber	Assignment	Test Match	Placebo Interference
1702	C=O Stretch	Present	Absent
2900	CH Stretch	Present	Absent

Revision History:

Revision Date	Revision No.	Details	Reason	Approved By
04/05/2025	2.0	Added spectral match overlay percentage and placebo interference criteria	Annual Review