SOP Guide for Pharma

Elixir Department: SOP for Preservative Content Assay – V 2.0

Elixir Department: SOP for Preservative Content Assay – V 2.0

Standard Operating Procedure for Assay of Preservative Content in Elixir Formulations

Department Elixir Department
SOP No. SOP/ELX/230/2025
Supersedes SOP/ELX/230/2022
Page No. Page 1 of 8
Issue Date 11/04/2025
Effective Date 15/04/2025
Review Date 11/04/2026

1. Purpose

To outline a validated procedure for the quantitative estimation of preservatives (e.g., methylparaben, propylparaben, benzoic acid, sorbic acid) in elixir formulations using High Performance Liquid Chromatography (HPLC) or other appropriate analytical techniques.

2. Scope

This SOP applies to the Quality Control Department for testing preservative content during batch release, stability studies, and formulation development of elixirs containing antimicrobial preservatives.

3. Responsibilities

  • QC Analyst:
    • Prepare samples and standards, perform the assay, and record observations.
  • QC Supervisor:
    • Verify calibration, system suitability, and review results for compliance.
  • QA Officer:
    • Review analytical results, ensure alignment with specification, and approve for batch release.

4. Accountability

The QC Head is accountable for the accuracy and reliability of the preservative content assay. The QA Head ensures regulatory compliance and documentation integrity.

5. Procedure

5.1 Equipment and Materials

  • HPLC system with
UV detector
  • Column: C18, 250 mm × 4.6 mm, 5 µm
  • Preservative reference standards (e.g., methylparaben, propylparaben)
  • Mobile phase: typically methanol:buffer or acetate buffer mixtures
  • Filtration system with 0.45 µm filters
  • 5.2 Preparation of Standards

    1. Weigh and dissolve appropriate quantity of preservative standard in mobile phase.
    2. Prepare working standard solution at expected concentration range (e.g., 50–150% of label claim).

    5.3 Sample Preparation

    1. Accurately measure and dilute elixir sample using mobile phase.
    2. Filter the solution through a 0.45 µm membrane before injection.

    5.4 Chromatographic Conditions

    • Detector wavelength: 254 nm (typical for parabens and benzoates)
    • Injection volume: 20 µL
    • Flow rate: 1.0 mL/min
    • Run time: 10–20 minutes depending on separation profile

    5.5 System Suitability

    1. Resolution between preservatives: NLT 1.5
    2. RSD of peak area from 5 injections of standard: NMT 2.0%
    3. Retention time of preservative peaks within validated range

    5.6 Calculation

    Preservative Content (%) = (Sample peak area / Standard peak area) × (Standard concentration / Sample concentration) × 100

    5.7 Acceptance Criteria

    1. Methylparaben: 90–110% of labeled amount
    2. Propylparaben: 90–110% of labeled amount
    3. Benzoic acid/Sorbic acid: Within validated range or pharmacopeial limits

    5.8 Documentation

    1. Record chromatograms, peak areas, and calculation details in the Preservative Assay Logbook (Annexure-1).
    2. Attach printouts and retain with BMR.
    3. Document standard preparation details and system suitability parameters.

    6. Abbreviations

    • SOP: Standard Operating Procedure
    • HPLC: High Performance Liquid Chromatography
    • QC: Quality Control
    • QA: Quality Assurance
    • RSD: Relative Standard Deviation

    7. Documents

    1. Preservative Assay Logbook (Annexure-1)
    2. Instrument Calibration Record
    3. Batch Manufacturing Record (BMR)

    8. References

    • USP Monographs for Methylparaben, Propylparaben, Benzoic Acid, Sorbic Acid
    • ICH Q2(R1) – Validation of Analytical Procedures
    • 21 CFR Part 211.165 – Testing and Release for Distribution

    9. SOP Version

    Version: 2.0

    10. Approval Section

    Prepared By Checked By Approved By
    Signature
    Date
    Name
    Designation
    Department

    11. Annexures

    Annexure-1: Preservative Assay Logbook

    Date Batch No. Preservative Claim (%) Found (%) Pass/Fail Tested By Verified By
    11/04/2025 ELX-0425-048 Methylparaben 0.15% 0.148% Pass 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 Inclusion of alternative preservatives and system suitability Method Extension QA Head
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