department and covers redox titration methods using oxidizing or reducing agents such as potassium permanganate, iodine, potassium dichromate, and sodium thiosulfate in accordance with pharmacopoeial procedures.

3. Responsibilities

• Analytical Chemist: Develops and performs redox titration procedures, prepares reagents, documents observations, and compiles validation data.
• Reviewer: Ensures method reproducibility, accuracy of calculations, and regulatory compliance of the documentation.
• QA Officer: Verifies SOP alignment with regulatory and GMP requirements.
• Head – AMD: Authorizes the developed and validated method for implementation in QC or for regulatory submissions.

4. Accountability

The Head of the Analytical Method Development department is accountable for ensuring the robustness, reliability, and regulatory compliance of oxidation-reduction titration methods developed in the laboratory.

5. Procedure

5.1 Method Selection

1. Identify the analyte’s oxidation-reduction behavior and its compatibility with available titrants.
2. Select suitable redox reagent based on the redox potential, reaction conditions, and endpoint visibility. Examples:
   • Potassium permanganate (KMnO₄) – strong oxidizer, self-indicating
   • Sodium thiosulfate – reducing agent for iodine titrations
   • Potassium dichromate – used in presence of diphenylamine indicator
3. Document rationale in Annexure-1: Method Selection Record.

5.2 Reagent Preparation and Standardization

1. Prepare volumetric solutions of redox titrants using analytical-grade chemicals and TOC-free water.
2. Standardize:
   • KMnO₄ using oxalic acid
   • Sodium thiosulfate using iodine or potassium dichromate
   • Iodine using arsenic trioxide or sodium thiosulfate
3. Store reagents in amber bottles to avoid photodegradation where applicable.
4. Log preparation and standardization details in Annexure-2: Reagent Standardization Log.

5.3 Sample Preparation

1. Weigh the appropriate quantity of sample (e.g., 100–500 mg based on label claim).
2. Dissolve in compatible solvent such as water, dilute sulfuric acid, or dilute hydrochloric acid.
3. Apply heat or stirring if necessary to obtain complete dissolution.
4. Filter or centrifuge if the solution contains insoluble matter.
5. Record procedure in Annexure-3: Sample Preparation Log.

5.4 Titration Procedure

1. Transfer a known aliquot of the prepared sample solution to a titration flask.
2. Add appropriate medium (e.g., dilute H₂SO₄ for KMnO₄ titrations).
3. If required, add an indicator such as starch, diphenylamine, or ferroin.
4. Titrate slowly with standardized titrant until a stable color change occurs:
   • KMnO₄: Colorless to faint pink
   • Iodine: Blue to colorless (with starch)
   • Dichromate: Violet to green endpoint (with diphenylamine)
5. Repeat titration in triplicate and document volumes.
6. Enter titration data in Annexure-4: Titration Observation Sheet.

5.5 Calculation

% Assay = (V × N × Eq. Wt × 100) / W × 1000
Where:
V = Volume of titrant (mL)
N = Normality of titrant
Eq. Wt = Equivalent weight of analyte
W = Sample weight (mg)

5.6 Method Optimization

1. Optimize conditions by assessing:
   • Temperature effect on reaction completion
   • Stability of end-point color
   • Interference from excipients or matrix
   • Reaction completion time
2. Test alternative indicators where applicable and adjust titration speed.
3. Document observations in Annexure-5: Method Optimization Record.

5.7 Method Validation

1. Specificity: Test placebo or excipient matrix to ensure no endpoint interference.
2. Precision:
   • Repeatability (intra-day, six replicates): RSD ≤ 2.0%
   • Intermediate Precision (inter-day, analyst): RSD ≤ 2.0%
3. Accuracy: Spike recovery experiments at 80%, 100%, and 120% levels; acceptance criteria: 98–102%.
4. Linearity: Analyze 5 concentrations across 50–150% range; R² ≥ 0.999.
5. Robustness: Vary titrant concentration, indicator volume, and temperature ±5°C.
6. Summarize in Annexure-6: Validation Summary Report.

6. Abbreviations

• SOP: Standard Operating Procedure
• AMD: Analytical Method Development
• RSD: Relative Standard Deviation
• Eq. Wt: Equivalent Weight
• TOC: Total Organic Carbon

7. Documents

1. Method Selection Record – Annexure-1
2. Reagent Standardization Log – Annexure-2
3. Sample Preparation Log – Annexure-3
4. Titration Observation Sheet – Annexure-4
5. Method Optimization Record – Annexure-5
6. Validation Summary Report – Annexure-6

8. References

• USP <541> – Titrimetry
• IP Appendix 3.6 – Redox Methods
• Ph. Eur. 2.2.20 – Redox Titrations
• ICH Q2(R1) – Validation of Analytical Procedures

9. SOP Version

Version: 2.0

10. Approval Section

	Prepared By	Checked By	Approved By
Signature
Date
Name
Designation
Department

11. Annexures

Annexure-1: Method Selection Record

Analyte	Titrant	Indicator	Medium	Analyst
Ascorbic Acid	Iodine	Starch	Water	Sunita Reddy

Annexure-2: Reagent Standardization Log

Reagent	Strength	Standardized Against	Date
0.1 N KMnO₄	0.1001 N	Oxalic Acid	12/05/2025

Annexure-3: Sample Preparation Log

Sample	Weight	Solvent	pH
Ferrous Sulfate	250 mg	1 N H₂SO₄	~1.5

Annexure-4: Titration Observation Sheet

Trial	Volume Used (mL)	Endpoint Observed	% Assay
1	15.2	Pale pink	99.1%

Annexure-5: Method Optimization Record

Parameter	Tested Variation	Observation	Conclusion
Temperature	Room vs. 40°C	Faster reaction at 40°C	Recommended

Annexure-6: Validation Summary Report

Parameter	Criteria	Result	Status
Accuracy	98–102%	99.3%	Pass
Precision	RSD ≤ 2.0%	0.84%	Pass
Linearity	R² ≥ 0.999	0.9991	Pass

Revision History:

Revision Date	Revision No.	Details	Reason	Approved By
04/05/2025	2.0	Expanded titrant list and validation parameters	Annual SOP Review