Standard Operating Procedure for pH Drift Analysis in Elixir Formulations

Department	Elixir Department
SOP No.	SOP/ELX/233/2025
Supersedes	SOP/ELX/233/2022
Page No.	Page 1 of 7
Issue Date	11/04/2025
Effective Date	15/04/2025
Review Date	11/04/2026

1. Purpose

To define the procedure for performing pH drift analysis of elixir formulations to monitor and evaluate the stability of pH under different storage conditions and time intervals as a part of formulation robustness and shelf-life assessment.

2. Scope

This SOP applies to the Quality Control and Formulation Development Departments for evaluating pH variation in elixirs during product development, scale-up, batch release, and stability testing.

3. Responsibilities

• QC Analyst:
  • Perform pH testing at designated intervals and record results accurately.
• Formulation Scientist:
  • Interpret results for formulation suitability and recommend buffering strategies.
• QA Officer:
  • Ensure that results are documented as per regulatory and internal SOPs.

4. Accountability

The QC Head is accountable for execution of the test as per this SOP. The QA Head is responsible for compliance of pH drift analysis results with internal quality and regulatory standards.

5. Procedure

5.1 Equipment and Materials

• Calibrated digital pH meter with temperature compensation
• Standard buffer solutions (pH 4.0, 7.0, 10.0)
• Elixir sample
• Glass beaker, magnetic stirrer, and thermometer

5.2 Calibration of pH Meter

1. Calibrate the pH meter daily before use using buffer solutions at pH 4.0, 7.0, and 10.0.
2. Ensure calibration slope is within acceptable range (95%–105%).
3. Document calibration details in the pH Meter Calibration Log.

5.3 Sample Storage for Drift Analysis

1. Store the same batch of elixir at multiple conditions:
   • 25°C ± 2°C / 60% RH ± 5% RH (long-term)
   • 40°C ± 2°C / 75% RH ± 5% RH (accelerated)
   • Refrigerated condition (if applicable)
2. Protect light-sensitive samples from exposure using amber containers or aluminum foil.

5.4 Time Points for pH Testing

1. Initial (0 Day)
2. 1 Day
3. 3 Days
4. 7 Days
5. 14 Days
6. 1 Month, 3 Months, 6 Months, and beyond (for real-time stability)

5.5 Testing Procedure

1. Take 50 mL of the elixir sample into a clean beaker.
2. Place the beaker on a magnetic stirrer and allow uniform mixing.
3. Insert the pH electrode and wait for a stable reading (±0.02 pH units variation).
4. Record the reading along with the storage condition and date.

5.6 Evaluation and Acceptance Criteria

1. Compare the pH values across all intervals.
2. Drift of ±0.3 pH units from initial value is acceptable unless otherwise validated.
3. Any trend of continuous drift must be investigated for formulation instability or microbial contamination.

5.7 Documentation

1. Enter the results in the pH Drift Monitoring Logbook (Annexure-1).
2. Attach graph of pH over time and include in formulation stability report.
3. Record calibration status and analyst initials for each reading.

6. Abbreviations

• SOP: Standard Operating Procedure
• pH: Potential of Hydrogen
• RH: Relative Humidity
• QA: Quality Assurance
• QC: Quality Control

7. Documents

1. pH Drift Monitoring Logbook (Annexure-1)
2. Stability Study Summary Report
3. pH Meter Calibration Log

8. References

• USP Chapter <791> – pH
• ICH Q1A(R2) – Stability Testing of New Drug Substances and Products
• 21 CFR Part 211.160 – Laboratory Controls

9. SOP Version

Version: 2.0

10. Approval Section

	Prepared By	Checked By	Approved By
Signature
Date
Name
Designation
Department

11. Annexures

Annexure-1: pH Drift Monitoring Logbook

Date	Batch No.	Storage Condition	Time Point	pH Value	Initial pH	Drift	Tested By	Verified By
11/04/2025	ELX-0425-050	40°C / 75% RH	Day 7	5.62	5.75	-0.13	Rajesh Kumar	Sunita Reddy

Revision History:

Revision Date	Revision No.	Revision Details	Reason for Revision	Approved By
01/01/2024	1.0	Initial SOP Release	New SOP Creation	QA Head
11/04/2025	2.0	Added long-term trend analysis and acceptance criteria	Scientific Enhancement	QA Head