or UV spectrophotometry.

2. Scope

This SOP applies to the Analytical Method Development and Quality Control departments involved in the sampling, testing, and evaluation of blend uniformity for solid oral dosage forms (e.g., tablets and capsules).

3. Responsibilities

• Formulation Chemist: Provides blended powder and sampling plan for analysis.
• Analytical Scientist: Develops and validates the assay method and performs blend analysis.
• QA Executive: Verifies compliance with regulatory standards and approves results.

4. Accountability

The Head of Analytical Method Development is accountable for ensuring that blend uniformity results accurately reflect the homogeneity of the final dosage form and support batch release decisions.

5. Procedure

5.1 Sampling Strategy

1. Collect 10–20 samples from different locations of the blender (top, middle, bottom, left, right, center).
2. Each sample should weigh at least 1.0 g or as per assay requirement.
3. Use sampling thieves or in-line sampling systems, following GMP protocols.

5.2 Sample Preparation

1. Accurately weigh a portion of each blend sample equivalent to one dosage unit.
2. Dissolve in suitable solvent (e.g., diluent: methanol or phosphate buffer), sonicate, and filter through 0.45 µm membrane.
3. Dilute to desired concentration for analysis.

5.3 Standard Preparation

1. Prepare a stock solution of API in the same diluent.
2. Prepare working standard to match the sample concentration.

5.4 HPLC/UV Conditions

• HPLC Column: C18, 250 mm × 4.6 mm, 5 µm
• Mobile Phase: Buffer:Acetonitrile (60:40) or as optimized
• Detection: UV at λmax of the API (e.g., 254–280 nm)
• Injection Volume: 20 µL

5.5 Evaluation Criteria

1. Calculate % label claim of each sample against standard.
2. Determine % Relative Standard Deviation (RSD) across all samples.
3. Acceptance Criteria:
   • Each sample should be within 85%–115% of target content.
   • RSD should not exceed 5.0% (unless otherwise justified).

5.6 Validation Parameters

1. Specificity: Assay method should distinguish API from excipients.
2. Linearity: r² ≥ 0.999 over 50%–150% of working concentration.
3. Accuracy: Recovery within 98%–102% for spiked placebo blends.
4. Precision: RSD ≤ 2% for replicate analysis.
5. Robustness: Minor changes in flow rate, detection wavelength, or pH should not affect results.

6. Abbreviations

• API: Active Pharmaceutical Ingredient
• RSD: Relative Standard Deviation
• GMP: Good Manufacturing Practice
• HPLC: High Performance Liquid Chromatography

7. Documents

1. Blend Uniformity Sampling Log – Annexure-1
2. Blend Uniformity Assay Report – Annexure-2
3. Method Validation Summary – Annexure-3

8. References

• ICH Q2(R1): Validation of Analytical Procedures
• FDA Guidance for Industry: Blend Uniformity Analysis
• USP <905>: Uniformity of Dosage Units

9. SOP Version

Version: 2.0

10. Approval Section

	Prepared By	Checked By	Approved By
Signature
Date
Name	Yogesh Pawar	Priya Dey	Sunita Reddy
Designation	Analytical Chemist	QA Reviewer	Head – AMD
Department	Analytical Method Development	QA	Analytical Method Development

11. Annexures

Annexure-1: Blend Uniformity Sampling Log

Location	Sample ID	Weight (mg)	Time	Operator
Top Left	BU-282-01	105	10:15 AM	Ravi Sharma

Annexure-2: Blend Uniformity Assay Report

Sample ID	% Assay	Acceptance Limit	Status
BU-282-01	98.5%	85–115%	Pass

Annexure-3: Method Validation Summary

The HPLC method for blend uniformity testing was validated for specificity, linearity, precision, and accuracy. All parameters met ICH Q2(R1) standards. Suitable for use in process validation and batch release.

Revision History:

Revision Date	Revision No.	Details	Reason	Approved By
21/05/2025	2.0	Integrated sampling strategy and updated validation ranges	Annual Review	Sunita Reddy
10/06/2022	1.0	Initial SOP Release	New SOP	QA Head