Standard Operating Procedure for Degradation Product Identification in Tablets

Department	Quality Control
SOP No.	SOP/TAB/108/2025
Supersedes	SOP/TAB/108/2022
Page No.	Page 1 of 7
Issue Date	01/03/2026
Effective Date	06/03/2026
Review Date	01/03/2027

1. Purpose

To define the procedure for identifying degradation products in tablet formulations, ensuring that degradation products are detected and quantified in accordance with regulatory standards.

2. Scope

This SOP applies to the identification and quantification of degradation products in tablets using appropriate analytical techniques, such as High-Performance Liquid Chromatography (HPLC), Gas Chromatography (GC), or Mass Spectrometry (MS).

3. Responsibilities

• Quality Control (QC): Responsible for performing the degradation product identification and ensuring compliance with established specifications for tablet formulations.
• Quality Assurance (QA): Reviews and approves the degradation product analysis results and ensures adherence to regulatory standards.
• Laboratory Personnel: Responsible for sample preparation, conducting the tests, and ensuring the accuracy of the analytical techniques used for degradation product identification.

4. Accountability

The QC Manager is accountable for ensuring that degradation product identification is performed accurately and in compliance with product specifications. The QA Manager is responsible for reviewing and approving the results before the product can be released.

5. Procedure

5.1 Sample Preparation

1. Obtain a representative sample of the tablets to be tested (usually 10–20 tablets depending on batch size).
2. Crush the tablets into a fine powder using a mortar and pestle or mechanical grinder to ensure homogeneity.
3. Weigh an appropriate amount of the powdered sample (e.g., 100 mg) for analysis.
4. Prepare a dissolution solution or extraction solvent as per the degradation product analysis method (e.g., water, methanol, or a mixture of solvents).
5. Dissolve or extract the sample as per the method required for degradation product identification.

5.2 Analytical Method Selection

1. Choose an appropriate analytical method based on the nature of the degradation products. Common methods include:
   • HPLC for polar and moderately non-polar degradation products.
   • GC for volatile degradation products.
   • MS for detailed structural analysis and identification.
2. Ensure that the analytical method is validated and capable of detecting degradation products at the required levels of sensitivity and specificity.

5.3 Degradation Product Analysis

1. Run the prepared sample through the selected analytical instrument according to the method-specific conditions (e.g., column type, mobile phase, flow rate for HPLC, temperature conditions for GC, or mass spectrometer settings).
2. Record the chromatographic or spectral data generated during the analysis.
3. Monitor the retention times, peaks, and spectra for potential degradation products.
4. Compare the results with the chromatogram or spectrum of a blank sample and a standard reference to identify and quantify degradation products.

5.4 Data Interpretation

1. Identify peaks corresponding to known degradation products or new peaks that may suggest the presence of degradation products.
2. Compare the results with the product’s stability specifications and established degradation pathways to determine if any identified products are within acceptable limits.
3. Quantify the degradation products by comparing the peak areas or heights with the calibration curve for each degradation product.
4. If necessary, perform further analysis using advanced techniques (e.g., MS or NMR) to confirm the structure of the identified degradation products.

5.5 Acceptance Criteria

1. Ensure that the amount of each degradation product identified does not exceed the predetermined limits set by regulatory standards (e.g., <0.1% or <1% of the total content depending on the drug and degradation profile).
2. If the degradation products exceed acceptable limits, initiate an investigation and corrective actions as necessary.
3. Document any deviations in the deviation report (Annexure-1) and evaluate the potential impact on product quality and safety.

5.6 Documentation and Record-Keeping

1. Document all degradation product analysis results, including the chromatographic or spectral data, identification and quantification of degradation products, and any deviations in the batch record (Annexure-2).
2. Ensure that all records are signed, dated, and stored according to the company’s record retention policy for future audits and inspections.
3. Maintain raw data, including chromatograms, spectra, and calibration curves, for regulatory compliance and future reference.

5.7 Post-Test Actions

1. Clean the laboratory equipment and instruments used in the degradation product analysis according to the equipment’s SOP to avoid cross-contamination between tests.
2. Dispose of used samples, solvents, and reagents according to the company’s waste disposal procedures.
3. Ensure that the laboratory instruments used for degradation product analysis are calibrated and maintained according to their respective SOPs.

6. Abbreviations

• SOP: Standard Operating Procedure
• GMP: Good Manufacturing Practice
• QC: Quality Control
• QA: Quality Assurance
• API: Active Pharmaceutical Ingredient
• HPLC: High-Performance Liquid Chromatography
• GC: Gas Chromatography
• MS: Mass Spectrometry

7. Documents

1. Batch Record (Annexure-2)
2. Deviation Report (Annexure-1)

8. References

• USP <701> – Dissolution Testing of Tablets
• 21 CFR Part 211 – Current Good Manufacturing Practice for Finished Pharmaceuticals (US FDA)
• European Pharmacopoeia (EP) – Specifications for Degradation Products

9. SOP Version

Version: 2.0

10. Approval Section

	Prepared By	Checked By	Approved By
Signature
Date
Name
Designation
Department

11. Annexures

Annexure-1: Deviation Report

Deviation Date	Batch Number	Deviation Description	Corrective Action	Responsible Person
15/12/2025	Batch 001	Degradation product exceeded limit	Investigated and reformulated	Jane Doe

Annexure-2: Batch Record

Batch Number	Degradation Product Identified	Concentration (ppm)	Result
Batch 001	Degradation Product A	0.05	Pass

Revision History:

Revision Date	Revision No.	Revision Details	Reason for Revision	Approved By
01/01/2024	1.0	Initial Version	New SOP Creation	QA Head
01/02/2025	2.0	Updated Analytical Method	Improved detection method for degradation products	QA Head