Elixir Department: SOP for Heavy Metal Testing – V 2.0

Standard Operating Procedure for Heavy Metal Testing in Elixir Formulations

Department	Elixir Department
SOP No.	SOP/ELX/222/2025
Supersedes	SOP/ELX/222/2022
Page No.	Page 1 of 9
Issue Date	11/04/2025
Effective Date	15/04/2025
Review Date	11/04/2026

1. Purpose

To define the procedure for the qualitative and/or quantitative testing of heavy metals in elixir formulations using validated analytical methods such as ICP-MS, AAS, or colorimetric methods, in accordance with pharmacopeial and regulatory requirements.

2. Scope

This SOP applies to finished elixir products that are tested for the presence of heavy metals including, but not limited to, lead (Pb), arsenic (As), mercury (Hg), and cadmium (Cd) as part of batch release and stability studies.

3. Responsibilities

QC Analyst:
- Prepare samples and standards, conduct testing, and record results.
QC Supervisor:
- Verify test methods, calibration status, and ensure result accuracy.
QA Officer:
- Review and approve final reports, investigate OOS results if required.

4. Accountability

The QC Head is accountable for the execution and review of heavy metal testing procedures. The QA Head is responsible for ensuring regulatory compliance and batch release decisions based on test outcomes.

5. Procedure

5.1 Sample Preparation

Take an appropriate quantity of the elixir sample (as per method SOP, typically 10–20 mL).
Digest the sample using wet digestion method with nitric acid and hydrogen peroxide under a fume hood.
Filter and dilute the digest to a known volume with deionized water before analysis.

5.2 Standard Preparation

Prepare calibration standards for lead, arsenic, mercury, and cadmium at known concentrations as per validation protocol.
Include a blank and quality control standards in each analytical run.

5.3 Instrumental Parameters (ICP-MS/AAS)

ICP-MS: Preferred for trace level detection; sensitivity up to ppt.
AAS: Use graphite furnace or hydride generation as per analyte requirement.
Ensure instruments are calibrated and performance-verified before use.

5.4 Colorimetric Method (Optional)

Follow USP <231> or other validated method for total heavy metal estimation (as Pb).
Compare color intensity with lead reference standard after reaction with sodium sulfide or dithizone reagent.

5.5 Acceptance Criteria

Heavy metal content should comply with product specification:
- Lead (Pb): NMT 0.5 ppm
- Arsenic (As): NMT 1.5 ppm
- Mercury (Hg): NMT 0.1 ppm
- Cadmium (Cd): NMT 0.2 ppm
For total heavy metals (as Pb), NMT 10 ppm unless otherwise justified.

5.6 Documentation

Record all data in the Heavy Metal Testing Logbook (Annexure-1).
Attach chromatograms, calibration curves, and raw data to the batch file.
Cross-verify results with QA before batch release.

6. Abbreviations

ICP-MS: Inductively Coupled Plasma Mass Spectrometry
AAS: Atomic Absorption Spectroscopy
SOP: Standard Operating Procedure
QC: Quality Control
QA: Quality Assurance
ppm: Parts Per Million

7. Documents

Heavy Metal Testing Logbook (Annexure-1)
Instrument Calibration Records
Batch Manufacturing Record (BMR)

8. References

USP Chapter <233> – Elemental Impurities
ICH Q3D – Guideline for Elemental Impurities
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: Heavy Metal Testing Logbook

Date	Batch No.	Pb (ppm)	As (ppm)	Hg (ppm)	Cd (ppm)	Method	Tested By	Verified By
11/04/2025	ELX-0425-040	0.3	0.8	<0.05	0.1	ICP-MS	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	QA Head
11/04/2025	2.0	Inclusion of ICP-MS and updated limits per ICH Q3D	Regulatory Alignment	QA Head