Sulphated Ash Test (Residue on Ignition Test) In Pharmaceuticals: Why & How

Sulphated Ash Test In Pharmaceutical Analysis: The Sulphated Ash Test (also known as Residue on Ignition Test) is a quality control procedure used in pharmaceutical analysis to determine the amount of inorganic residue remaining after a sample is incinerated in the presence of sulfuric acid. This residue typically consists of metal salts and other inorganic impurities

Sulphated Ash Test In Pharmaceutical Analysis

The sulphated ash test is a pharmaceutical analysis technique used to quantify the amount of inorganic impurities present in a sample. Primarily applied in quality control, the test involves incinerating the sample in the presence of concentrated sulfuric acid, which facilitates the complete oxidation of organic matter into volatile gases. The remaining non-volatile residue, composed mainly of inorganic salts such as metal sulfates, is then weighed. This method plays a critical role in ensuring the purity and quality of pharmaceutical substances by detecting potential contaminants introduced during manufacturing, handling, or storage.

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Why is the sulphated ash test done?

The Sulphated Ash Test is performed to

• Detect and quantify inorganic impurities (e.g., metal oxides, silicates, and sulfates) that may come from:
  • Raw materials
  • Manufacturing processes
  • Contaminants
  • Containers or closures

• To ensure product purity and safety, especially for:
  • Active pharmaceutical ingredients (APIs)
  • Excipients
  • Finished drug products

• To comply with pharmacopeial standards like USP, BP, EP, or IP, which specify limits for inorganic residues.

Principle of the Sulphated Ash Test

The sample is ignited at a high temperature in the presence of concentrated sulfuric acid, which helps to convert inorganic materials into stable sulfates. The remaining residue is weighed, and its amount (as a percentage of the original sample) is calculated.

How is the sulphated ash test done?

Materials Needed:

• Silica or platinum crucible
• Muffle furnace
• Concentrated sulfuric acid (H₂SO₄)
• Analytical balance

Procedure:

1. Preparation:
   • Clean and ignite the crucible at about 600 ± 50 °C until it reaches a constant weight.
   • Cool in a desiccator and weigh (W₁).
2. Sample Addition:
   • Weigh a known quantity of the sample (e.g., 1–2 g) into the crucible.
   • Moisten with a small amount of concentrated sulfuric acid (typically a few drops).
3. Charring:
   • Heat gently over a low flame or hot plate to char the organic matter (avoid splattering).
   • After charring, transfer the crucible to a muffle furnace.
4. Ignition:
   • Ignite at 600 ± 25 °C for 30 minutes or until the sample is white or nearly white.
   • If necessary, repeat the addition of H₂SO₄ and ignition to ensure complete oxidation.
5. Cooling and Weighing:
   • Cool the crucible in a desiccator.
   • Weigh the residue (W₂)

Calculation Formula:

Acceptance Criteria

The result must comply with the pharmacopeial limit, often not more than 0.1–0.2%, depending on the substance.

Safety Precautions

• Use sulfuric acid in a fume hood due to toxic fumes.
• Avoid loss of sample during heating.
• Ensure complete combustion for accurate results.

Case Study: Sulphated Ash Test

To determine the percentage of sulphated ash in a given Active pharmaceutical ingredient (API):

Sample Details:

• Crucible weight (W₁) = 30.254 g
• Crucible + Sample before ignition = 32.254 g
• Sample weight = 32.254 g – 30.254 g = 2.00 g
• Crucible + Residue after ignition (W₂) = 30.276 g

Calculation:

Residue weight=W2​−W1​=30.276−30.254=0.022g

% of Sulphated Ash (Using formula -1) = (0.022/2.00) x 100 = 1.1%

Note: If the limit is NMT (Not More Than) 0.1%, then the API fails in the test

Difference Between Sulphated Ash and Residue on Ignition

Note:

• Use Sulphated Ash when precise determination of inorganic impurities is required, and sulfuric acid helps ensure full conversion to stable sulfates.
• Use Residue on Ignition for a broader assessment of total residue, especially when acid treatment is unnecessary or not specified.

Conclusion

The sulphated ash content of the tested pharmaceutical sample was found to be 1.10% w/w, calculated based on the residue remaining after ignition in the presence of sulfuric acid. This result provides a quantitative estimate of the total inorganic impurities present in the sample, which may originate from manufacturing residues, excipients, or contamination.

Upon comparing the result with the applicable pharmacopeial limit, it was observed that:

• If the pharmacopeial specification allows a maximum of 2.0%, the sample complies with the requirement.
• However, if the specified limit is not more than 0.1%, the sample does not comply and may indicate poor raw material quality or contamination during processing.

This test is crucial in ensuring the purity, safety, and quality of pharmaceutical substances. Results above acceptable limits necessitate further investigation and possibly corrective actions in the manufacturing or sourcing process.

FAQs on Sulphated Ash Test

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• The 7 Key Differences Between Validation and Verification

Reference:

• India Pharmacopoeia (IP)
• British Pharmacopoeia (BP)
• United States Pharmacopeia (USP