consistency and regulatory compliance.

2. Scope

This SOP applies to the Analytical Method Development (AMD) department involved in designing, validating, and transferring pH measurement methods for all sterile injectable formulations, including solutions, suspensions, and emulsions.

3. Responsibilities

• Analytical Scientist: Develops and validates the pH measurement method, including buffer preparation and calibration.
• QC Analyst: Performs routine testing based on the developed method post-validation.
• QA Executive: Reviews pH data and ensures adherence to ICH and pharmacopeial standards.

4. Accountability

The Head of Analytical Method Development is accountable for finalizing the method, overseeing its validation, and ensuring pH testing for injections is accurate and GMP-compliant.

5. Procedure

5.1 Instrumentation and Calibration

1. Use a pH meter with automatic temperature compensation (ATC) and a combined glass electrode.
2. Calibrate the meter daily before use with standard buffer solutions at pH 4.00, 7.00, and 9.20 (Annexure-1).
3. Record slope, offset, and calibration validity. Acceptable slope range: 95%–105%.

5.2 Sample Preparation

1. Withdraw 2 mL of the injection solution aseptically into a clean beaker.
2. If the injection is viscous or opaque, dilute 1:1 with Water for Injection (WFI), unless otherwise specified.
3. Bring the solution to 25 ± 2°C before measurement.

5.3 Measurement

1. Rinse electrode with distilled water and blot dry with lint-free tissue.
2. Immerse electrode in sample ensuring complete submersion of the bulb and reference junction.
3. Allow reading to stabilize (within 30 seconds to 2 minutes).
4. Record pH value, sample ID, and time of measurement.
5. Rinse and recondition electrode if used continuously for more than 30 minutes.

5.4 Acceptance Criteria

• The pH of the injection must comply with the range specified in the product monograph or pharmacopeial monograph.
• Common injectable pH range: 3.0 – 9.0 depending on formulation type.
• Deviation outside specified range requires investigation and documentation.

5.5 Method Validation

1. Specificity: Method should give reproducible pH reading for API solution without interference from excipients.
2. Repeatability: RSD ≤ 0.5% over six replicates.
3. Robustness: Test with variations in temperature (±2°C) and stirring speed.

6. Abbreviations

• pH: Potential of Hydrogen
• ATC: Automatic Temperature Compensation
• QA: Quality Assurance
• AMD: Analytical Method Development
• WFI: Water for Injection

7. Documents

1. pH Measurement Log – Annexure-1
2. Calibration Record Sheet – Annexure-2
3. Validation Summary Report – Annexure-3

8. References

• USP <791>: pH Measurement
• ICH Q2(R1): Validation of Analytical Procedures
• Ph. Eur. 2.2.3: Potentiometric Determination of pH

9. SOP Version

Version: 2.0

10. Approval Section

	Prepared By	Checked By	Approved By
Signature
Date
Name	Neha Kulkarni	Vishal Pandey	Sunita Reddy
Designation	Analytical Scientist	QA Reviewer	Head – AMD
Department	Analytical Method Development	QA	Analytical Method Development

11. Annexures

Annexure-1: pH Measurement Log

Sample ID	Batch No.	Temperature (°C)	pH	Status
INJ-267-01	21052301	25.0	6.8	Pass

Annexure-2: Calibration Record Sheet

Buffer pH	Theoretical Value	Observed Value	Slope (%)	Status
4.00	4.00	4.01	100.1	Pass
7.00	7.00	7.01	—	—
9.20	9.20	9.18	99.8	Pass

Annexure-3: Validation Summary Report

The pH method was validated for injectable formulations including ceftriaxone and paracetamol injections. Results showed consistent readings within ±0.02 units, RSD ≤ 0.3%, and no impact from excipients or preservatives. Suitable for QC release and stability testing.

Revision History:

Revision Date	Revision No.	Details	Reason	Approved By
21/05/2025	2.0	Added robustness criteria and Annexure-3 summary	Annual Review	Sunita Reddy
01/04/2022	1.0	Initial SOP Release	New SOP	QA Head