SOP Guide for Pharma

Analytical Method Development: ATR-FTIR Method SOP – V 2.0

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Analytical Method Development: ATR-FTIR Method SOP – V 2.0

SOP for Attenuated Total Reflectance (ATR) FTIR Analysis in Analytical Method Development


Department Analytical Method Development
SOP No. SOP/AMD/097/2025
Supersedes SOP/AMD/097/2022
Page No. Page 1 of 14
Issue Date 19/05/2025
Effective Date 20/05/2025
Review Date 19/05/2026

1. Purpose

This SOP defines the standard procedure for conducting ATR-FTIR (Attenuated Total Reflectance – Fourier Transform Infrared) analysis for qualitative spectral fingerprinting and identity confirmation of Active Pharmaceutical Ingredients (APIs)

and excipients in the Analytical Method Development (AMD) laboratory.

2. Scope

This SOP is applicable to all APIs, excipients, and intermediates analyzed by ATR-FTIR spectroscopy in the AMD lab. It includes spectrum acquisition, fingerprint region comparison, and spectral overlay for conformity analysis.

3. Responsibilities

  • Analytical Chemist: Performs sample mounting, spectrum scanning, and initial data analysis.
  • Reviewer: Validates peak interpretation and comparison with reference standard.
  • QA Officer: Ensures documentation compliance and audit readiness.
  • Head – AMD: Reviews and approves spectrum interpretation and records.

4. Accountability

The Head of Analytical Method Development is accountable for the reliability, integrity, and regulatory compliance of ATR-FTIR spectral analyses performed within the lab.

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5. Procedure

5.1 Instrument Qualification and Readiness

  1. Ensure the ATR-FTIR instrument is qualified as per the equipment qualification SOP.
  2. Verify crystal integrity, cleanliness, and absence of scratches or contamination.
  3. Calibrate using polystyrene film (peaks at ~1601 cm-1 and 1154 cm-1) for wavelength accuracy.
  4. Record in Annexure-1: Instrument Qualification Log.

5.2 Sample Preparation and Handling

  1. Use finely powdered dry API or excipient material (moisture-free).
  2. Do not grind hygroscopic substances under high humidity; store in desiccator prior to use.
  3. Clean ATR crystal with isopropyl alcohol and lint-free tissue before sample application.
  4. Mount a small amount of sample (approx. 1–2 mg) onto the crystal ensuring full contact.
  5. Apply pressure using the integrated pressure arm of the ATR unit.
  6. Record sample details in Annexure-2: Sample Log Sheet.

5.3 Background and Sample Scan

  1. Background Collection: Run background scan using clean ATR crystal. Ensure spectrum is free of moisture or CO2 interference.
  2. Sample Scan Parameters:
    • Scan Range: 4000–400 cm-1
    • Resolution: 4 cm-1
    • Number of Scans: 32–64 (as per sensitivity requirement)
    • Mode: Absorbance
  3. Record scan settings in Annexure-3: Scan Parameter Log.
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5.4 Fingerprint Region Evaluation

  1. Focus interpretation in the fingerprint region (1800–600 cm-1) which is compound-specific.
  2. Evaluate peak position, intensity, and overall profile.
  3. Key functional groups:
    • C=O: ~1700 cm-1
    • CH stretching: ~2900–3000 cm-1
    • OH/NH stretch: ~3200–3500 cm-1
  4. Overlay with reference standard spectra to confirm match.
  5. Document observations in Annexure-4: Spectral Interpretation Sheet.

5.5 Acceptance Criteria

  1. Peak pattern and intensity must match reference standard.
  2. Relative intensity of major peaks should be consistent (±10% tolerance).
  3. Presence of any unexpected peaks indicates possible contamination or polymorphic variation.
  4. Overlay match ≥ 95% required for identity confirmation.
  5. Record overlay results in Annexure-5: Spectrum Comparison Report.

5.6 Precautions

  1. Do not overload crystal with sample; a thin uniform layer is sufficient.
  2. Handle samples with gloves to prevent contamination.
  3. Use desiccated storage for both samples and standards.
  4. Clean ATR crystal immediately after each scan.

6. Abbreviations

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

7. Documents

  1. Instrument Qualification Log – Annexure-1
  2. Sample Log Sheet – Annexure-2
  3. Scan Parameter Log – Annexure-3
  4. Spectral Interpretation Sheet – Annexure-4
  5. Spectrum Comparison Report – Annexure-5
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8. References

  • ICH Q2(R1) – Validation of Analytical Procedures
  • USP <197K> – Infrared Spectrophotometry
  • Pharmaceutical FTIR Analysis Texts
  • ATR-FTIR Instrument Manufacturer’s Manual

9. SOP Version

Version: 2.0

10. Approval Section

Prepared By Checked By Approved By
Signature
Date
Name
Designation
Department

11. Annexures

Annexure-1: Instrument Qualification Log

Date Check Performed Standard Used Result
19/05/2025 Wavelength Accuracy Polystyrene Pass

Annexure-2: Sample Log Sheet

Sample ID Compound Name Preparation Method Operator
ATR-097 Ibuprofen ATR Direct Application Rajesh Kumar

Annexure-3: Scan Parameter Log

Scan Range Resolution No. of Scans Mode
4000–400 cm-1 4 cm-1 64 Absorbance

Annexure-4: Spectral Interpretation Sheet

Wavenumber (cm-1) Functional Group Peak Intensity Comment
1708 C=O Stretch Strong Expected
2952 CH Stretch Medium Expected

Annexure-5: Spectrum Comparison Report

Sample Spectrum Reference Spectrum Match (%) Status
ATR-097 STD-097 97.5% Pass

Revision History:

Revision Date Revision No. Details Reason Approved By
04/05/2025 2.0 Integrated overlay match criteria and improved precautionary guidelines Annual SOP Review
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