Introduction
Ethylene Glycol (EG) and Diethylene Glycol (DEG) are toxic industrial chemicals that should not be present at unacceptable levels in pharmaceutical products. They have historically been associated with contamination of liquid medicines, particularly oral liquid formulations such as syrups, suspensions and solutions.
The issue has received renewed international attention following multiple incidents involving contaminated medicines and pharmaceutical raw materials. In October 2025, the World Health Organization (WHO) issued a Medical Product Alert concerning three substandard oral liquid medicines identified in India in which DEG contamination was reported.
For pharmaceutical manufacturers, the key lesson is that raw-material qualification, supplier control, incoming-material testing and finished-product verification are critical components of pharmaceutical quality assurance.
What Are Ethylene Glycol and Diethylene Glycol?
Ethylene Glycol (EG)
Ethylene Glycol is a colourless, odourless liquid primarily used in industrial applications such as antifreeze and chemical manufacturing.
It is toxic when ingested and can cause serious systemic toxicity, including metabolic disturbances and kidney injury.
Diethylene Glycol (DEG)
Diethylene Glycol is another industrial chemical used in applications such as solvents and chemical manufacturing. Like EG, it is toxic when consumed and can cause severe health effects.
Neither EG nor DEG should be present in pharmaceutical formulations at unacceptable levels.
WHO identifies both compounds as toxic substances that can be fatal when consumed, particularly in children.How Can EG and DEG Enter Pharmaceutical Products?
Contamination can occur when pharmaceutical raw materials or excipients are contaminated, substituted, incorrectly supplied, or inadequately controlled. Particular attention is required for excipients such as:
- Propylene Glycol
- Glycerin/Glycerol
- Sorbitol
- Other liquid excipients where contamination or substitution is a potential risk
WHO has specifically advised manufacturers of oral liquid medicines to test incoming batches of at-risk raw materials for EG and DEG before using them in production.
Potential sources of contamination include:
- Contaminated raw materials
- Falsified or adulterated excipients
- Supplier quality failures
- Inadequate material qualification
- Incorrect identification of raw materials
- Poor supply-chain controls
- Cross-contamination during handling or storage
Therefore, EG/DEG control should begin at the raw-material stage, rather than relying only on finished-product testing.
Why Are EG and DEG a Serious Pharmaceutical Safety Concern?
EG and DEG contamination is particularly dangerous because affected products may appear normal in terms of colour, appearance, odour and packaging
Contamination may therefore remain undetected without appropriate analytical testing.
WHO has reported multiple incidents involving contaminated oral liquid medicines and has emphasized increased surveillance and diligence across pharmaceutical supply chains.
Potential toxic effects of EG/DEG exposure can include:
- Gastrointestinal symptoms
- Metabolic abnormalities
- Neurological effects
- Reduced or absent urine production
- Acute kidney injury
- Severe systemic toxicity
- Death in serious cases
Children may be particularly vulnerable because many contaminated products have historically involved paediatric oral liquid medicines.
Recent Regulatory and Global Safety Attention
The risk associated with EG and DEG is not a new pharmaceutical concern, but recent contamination incidents have reinforced the importance of robust analytical controls.
WHO reported in 2023 that multiple global medical product alerts had been issued concerning DEG/EG-contaminated oral medicines and developed analytical approaches to support testing capacity.In 2024, WHO again advised pharmaceutical manufacturers to test incoming batches of raw materials such as propylene glycol, sorbitol and glycerin/glycerol for EG and DEG before using them as excipients.
More recently, WHO’s October 2025 Medical Product Alert concerned DEG-contaminated oral liquid medicines identified in India.In March 2026, WHO also conducted regional training on EG/DEG detection in oral liquid medicines, including the use of thin-layer chromatography as a screening approach.
These developments demonstrate the continuing importance of EG/DEG surveillance and laboratory capacity.Which Pharmaceutical Products Should Be Monitored?
EG/DEG testing is particularly relevant for products and raw materials where contaminated liquid excipients could enter the formulation. Examples include:
Oral Liquid Formulations
- Cough syrups
- Paediatric syrups
- Oral solutions
- Oral suspensions
- Other liquid oral dosage forms
Pharmaceutical Excipients
- Propylene Glycol
- Glycerin/Glycerol
- Sorbitol
- Other relevant liquid excipients
Raw Materials
Incoming raw materials should be evaluated based on their contamination risk, supplier history, regulatory requirements and intended use.
Why Raw-Material Testing Is Critical
A major quality-control principle for EG/DEG is prevention rather than detection after manufacture.
If a contaminated excipient enters production, the contaminant may be distributed throughout multiple finished-product batches.
Testing incoming high-risk raw materials can therefore provide an important control point.WHO specifically recommends testing each batch of incoming at-risk raw materials for EG and DEG before they are used as pharmaceutical excipients.
A robust raw-material control programme should include:- Approved supplier qualification
- Supplier audit and performance monitoring
- Certificate of Analysis review
- Identity verification
- Risk-based contaminant testing
- Batch traceability
- Retention samples
- Defined acceptance criteria
EG/DEG Testing in Pharmaceutical Products
Analytical testing provides quantitative evidence of whether EG and DEG are present within the applicable specification or limit.
Testing may be performed on:
- Pharmaceutical excipients
- Raw materials
- Finished oral liquid formulations
- Suspect or investigation samples
- Stability samples, where appropriate
- Market surveillance samples
Analytical Techniques for EG and DEG
- Gas Chromatography (GC)
Gas Chromatography is a widely used analytical approach for determining EG and DEG in pharmaceutical products.
WHO identifies GC as a suitable and widely used technique for testing pharmaceutical products for EG and DEG. Depending on the analytical method and laboratory capability, GC may be configured with an appropriate detector and validated for the relevant matrix.- Thin-Layer Chromatography (TLC)
WHO has also developed a two-level approach for laboratories with limited access to GC.
In this approach:
TLC screening → Suspect samples → Confirmatory GC analysis
The International Pharmacopoeia includes a test for EG and DEG in liquid preparations for oral use. WHO has described TLC as a first-line screening approach, with confirmation using more definitive analytical techniques where required.
- Method Validation and Analytical Quality
Because EG/DEG testing may involve low-level contamination assessment, laboratories should ensure that the analytical method is appropriate for the intended application.
Important analytical performance characteristics may include:
- Specificity
- Accuracy
- Precision
- Recovery
- Linearity
- Limit of Detection (LOD)
- Limit of Quantification (LOQ)
- System suitability
- Robustness
The method should be demonstrated to be suitable for the specific sample matrix and intended regulatory or specification requirement.
EG/DEG Testing Across the Pharmaceutical Supply Chain
An effective control strategy should not rely on a single test.
- Stage 1 – Supplier Qualification
Assess the supplier’s manufacturing controls, quality systems, traceability and material specifications.
- Stage 2 – Incoming Raw Material Testing
Test high-risk excipients and materials before they are released for manufacturing.
- Stage 3 – Manufacturing Controls
Maintain appropriate segregation, identification, traceability and material-handling controls.
- Stage 4 – Finished Product Verification
Where required by risk assessment, product specification or regulatory expectations, verify finished oral liquid formulations.
- Stage 5 – Investigation Testing
Where contamination is suspected, analytical testing can support root-cause investigations and product-risk assessment.
How Eureka Analytical Services Supports EG/DEG Testing
Eureka supports pharmaceutical manufacturers and raw-material suppliers with analytical testing solutions for Ethylene Glycol and Diethylene Glycol.
Testing Support
- EG analysis
- DEG analysis
- EG + DEG testing
- Pharmaceutical raw-material testing
- Pharmaceutical excipient testing
- Oral liquid formulation testing
- Contamination investigation support
Application Areas
Testing can support:
- Propylene Glycol
- Glycerin/Glycerol
- Sorbitol
- Oral syrups
- Oral solutions
- Oral suspensions
- Paediatric liquid formulations
- Other relevant pharmaceutical matrices
Other relevant pharmaceutical matrices
Eureka can support manufacturers with:
- Incoming raw-material verification
- Supplier qualification testing
- Batch-release testing
- Regulatory compliance testing
- Contamination investigation
- Analytical method support
- Quality-control programmes
The appropriate testing scope and acceptance criteria should be established based on the applicable pharmacopoeial, regulatory, product and customer requirements.
Best Practices for Pharmaceutical Manufacturers
Manufacturers can strengthen EG/DEG risk management by:
- Qualifying raw-material suppliers before procurement.
- Testing high-risk incoming excipients before use.
- Verifying the identity and authenticity of critical raw materials.
- Maintaining complete batch traceability.
- Reviewing supplier Certificates of Analysis critically rather than relying on documentation alone.
- Implementing risk-based contaminant testing.
- Maintaining appropriate specifications and analytical procedures.
- Investigating any unexpected analytical result promptly.
- Reviewing supply-chain risks when sourcing from new suppliers.
- Applying enhanced controls to liquid oral and paediatric formulations where appropriate.
Why EG/DEG Testing Should Be Part of a Risk-Based Quality Programme
EG and DEG contamination illustrates why pharmaceutical quality cannot depend solely on finished-product inspection.
A strong control strategy combines:
Supplier Qualification → Raw Material Verification → Analytical Testing → Manufacturing Controls → Finished Product Testing → Traceability
This approach helps manufacturers identify contamination risks earlier and reduce the possibility of unsafe products entering the market.
Key Takeaways
- Ethylene Glycol (EG) and Diethylene Glycol (DEG) are toxic contaminants of serious pharmaceutical safety concern.
- Oral liquid medicines and certain liquid excipients require particular attention. WHO has repeatedly emphasized stronger surveillance and testing following international contamination incidents.
- Propylene glycol, glycerin/glycerol and sorbitol are among the raw materials specifically highlighted by WHO for contamination-risk control.
- Gas Chromatography (GC) is a widely used analytical technique for EG/DEG determination.
- WHO's testing strategy also describes TLC as a screening approach followed by confirmatory testing, where appropriate.
- Testing incoming high-risk raw materials before use is an important preventive quality-control measure.
- A risk-based EG/DEG testing programme can strengthen pharmaceutical quality assurance and patient safety.
Frequently Asked Questions (FAQ)
1. What are Ethylene Glycol (EG) and Diethylene Glycol (DEG)?
EG and DEG are industrial chemicals that are toxic when ingested. They are not intended ingredients in pharmaceutical formulations and can pose serious health risks when present as contaminants.
2. Which pharmaceutical products are most at risk of EG/DEG contamination?
Particular attention is required for oral liquid formulations and raw materials such as propylene glycol, glycerin/glycerol and sorbitol, where contamination or substitution can introduce EG or DEG into the manufacturing process.
3. Should pharmaceutical raw materials be tested for EG and DEG?
WHO advises manufacturers of oral liquid medicines to test each batch of incoming at-risk raw materials for EG and DEG before using them as excipients.
4. How are EG and DEG detected?
Gas Chromatography is a widely used analytical technique for EG/DEG testing. WHO also describes a tiered approach in which TLC can be used for screening, followed by confirmatory testing where required.
5. Why is EG/DEG testing important for paediatric medicines?
Many historical contamination incidents have involved oral liquid medicines intended for children. Because EG and DEG are highly toxic, contamination of paediatric formulations can have severe consequences.
6.Can EG/DEG testing be performed on pharmaceutical excipients?
Yes. Testing can be performed on relevant pharmaceutical excipients and raw materials, including materials such as propylene glycol, glycerin/glycerol and sorbitol, depending on the risk assessment and intended application.
7. Can finished oral liquid formulations also be tested?
Yes. EG/DEG analysis can be applied to finished oral liquid formulations where required for regulatory compliance, quality control, investigation or risk assessment.
Official References
- World Health Organization (WHO) – Medical Product Alert N°5/2025: Substandard (Contaminated) Oral Liquid Medicines
- WHO – Diethylene Glycol (DEG) and Ethylene Glycol (EG) Contamination: Analytical Methods Developed for Testing Paediatric Medicines
- WHO – Medical Product Alert N°1/2024: Falsified/Contaminated USP/EP Propylene Glycol
- WHO – The International Pharmacopoeia, 12th Edition: Test for Diethylene Glycol and Ethylene Glycol in Liquid Preparations for Oral Use
- WHO Good Manufacturing Practices for Excipients Used in Pharmaceutical Products
- United States Pharmacopeia (USP) – Pharmaceutical Quality Standards for Relevant Excipients and Preparations
- European Pharmacopoeia (Ph. Eur.) – Applicable Requirements for Pharmaceutical Excipients and Preparations
Conclusion
The continuing occurrence of EG/DEG contamination incidents demonstrates the importance of robust pharmaceutical supply-chain controls and analytical verification.
For manufacturers of oral liquid medicines, testing should begin with the raw materials most susceptible to contamination, rather than relying solely on finished-product testing. Supplier qualification, material authentication, risk-based analytical testing, appropriate manufacturing controls and complete traceability together provide a stronger framework for preventing contamination.
With appropriate analytical testing and quality-control systems, pharmaceutical manufacturers can identify potential EG/DEG contamination risks before affected materials enter production and help protect the safety and quality of medicines.