methods to ensure product stability and regulatory compliance.

2. Scope

This SOP applies to the Analytical Method Development and Quality Control departments responsible for moisture determination in raw materials, intermediates, and finished powder formulations.

3. Responsibilities

• QC Analyst: Performs moisture content testing using LOD or Karl Fischer titration.
• Analytical Scientist: Develops and validates moisture determination methods.
• QA Executive: Reviews data and ensures compliance with pharmacopeial standards.

4. Accountability

The Head of Analytical Method Development is accountable for ensuring accurate and validated moisture content testing, proper instrument calibration, and adherence to specifications.

5. Procedure

5.1 Method Selection

• Loss on Drying (LOD): Suitable for thermally stable compounds; used for routine analysis.
• Karl Fischer Titration: Preferred for thermolabile or hygroscopic materials and for water-specific quantification.

5.2 Loss on Drying (LOD) Procedure

1. Switch on the LOD oven and set temperature as per specification (usually 105°C unless stated otherwise).
2. Weigh 1–2 g of sample into a pre-dried and tared LOD dish.
3. Dry in the oven for 3 hours or as validated.
4. Cool in desiccator and reweigh.
5. Calculate % moisture using the formula:
   Moisture (%) = [(Initial weight – Final weight) / Initial weight] × 100

5.3 Karl Fischer Titration Procedure

1. Use volumetric or coulometric KF titrator based on sample moisture content.
2. Weigh 50–300 mg of sample directly into titration vessel (or use methanol solution).
3. Titrate with Karl Fischer reagent until endpoint is reached (stable drift).
4. Calculate moisture content in % using software or manual calculation based on titrant volume and sample weight.

5.4 Validation Parameters

1. Specificity: Ensure no interference from excipients or volatile solvents.
2. Precision: RSD ≤ 2.0% for 6 replicates.
3. Accuracy: Recovery 98%–102% using water-spiked samples.
4. Linearity: For Karl Fischer method over 0.1%–10% moisture.

5.5 Acceptance Criteria

• Moisture content should comply with pharmacopeial or in-house specification (e.g., NMT 5.0%).

6. Abbreviations

• LOD: Loss on Drying
• KF: Karl Fischer
• RSD: Relative Standard Deviation
• QA: Quality Assurance

7. Documents

1. Moisture Content Raw Data Sheet – Annexure-1
2. LOD Weight Log – Annexure-2
3. Karl Fischer Titration Record – Annexure-3

8. References

• USP <921>: Water Determination
• ICH Q2(R1): Validation of Analytical Procedures
• Ph. Eur. 2.5.32: Loss on Drying

9. SOP Version

Version: 2.0

10. Approval Section

	Prepared By	Checked By	Approved By
Signature
Date
Name	Aditi Thakur	Rajiv Menon	Sunita Reddy
Designation	QC Analyst	QA Reviewer	Head – AMD
Department	Analytical Method Development	QA	Analytical Method Development

11. Annexures

Annexure-1: Moisture Content Raw Data Sheet

Sample ID	Initial Wt. (g)	Final Wt. (g)	% Moisture	Method	Status
MC-289-01	1.256	1.210	3.67%	LOD	Pass

Annexure-2: LOD Weight Log

Includes calibration, blank trial, and sample weights for each run. Oven temperature set and monitored at 105°C ± 2°C.

Annexure-3: Karl Fischer Titration Record

Sample ID	Wt. (mg)	Volume of KF (mL)	% Water	Result
MC-289-KF01	210	0.45	2.14%	Pass

Revision History:

Revision Date	Revision No.	Details	Reason	Approved By
21/05/2025	2.0	Added dual-method approach and updated validation criteria	Annual Review	Sunita Reddy
01/12/2022	1.0	Initial SOP Release	New SOP	QA Head