Ethylene glycol and diethylene glycol, chemical cousins, are mostly used as industrial antifreeze agents and solvents. They are highly poisonous because they cause acidosis in the body, kidney failures, and neurological damage, and thus are very dangerous when ingested. Historically, tragic events, which have occurred where DEG has been incorrectly or falsely replaced with safer and more costly glycerin or propylene glycol in medicinal syrups, have resulted in mass poisoning and fatalities. This has, in turn, necessitated strict regulatory systems wherein manufacturers and regulators test raw materials (particularly, glycerin, sorbitol, and propylene glycol) and finished products due to trace contamination of EG/DEG.
Fundamental Principles
Testing is because EG and DEG exhibit different chemical characteristics, which can be used to separate and identify them at low concentrations (parts per million, ppm) in complex matrices. The fundamental concept is the chromatographic separation with selective detection. The small, polar, and polyhydroxylated compounds EG and DEG are isolated as small molecules based on the difference between their partitioning with the mobile and stationary phases. Detection takes advantage of their inability to have a robust chromophore (for certain techniques, some derivatization is required) or their susceptibility to mass spectrometric or charged aerosol detection.
Regulatory Limits and Compliance
There are extremely strict regulatory limits because the compounds are toxic. In the case of pharmaceutical-grade glycerin, a generally acceptable value for each individual of EG and DEG is 0.1% (1000 ppm) or less. There are authorities and other tougher internal company specifications with limits as low as 10-50 ppm. It will not be possible to comply with the test; the absence of the test or the fact that the result is higher than the limit will require quarantine of the material batch as mandatory, investigation, and reporting. Warnings and advice that come with this testing are issued by the World Health Organization (WHO) and government agencies such as the FDA and EMA in various nations.
Challenges in Testing
Complexity of the matrix: Samples such as syrups have high contents of sugars, flavours, and active ingredients that may interfere with the analysis, thus demanding a good sample cleanup. Semblance to Other Substances: To separate EG and DEG not only between the two compounds and other glycols (such as triethylene glycol) but also between the two compounds and sugar alcohols, chromatographic resolution is needed. Sensitivity Requirements Sensitive instrumentation and careful technique are needed to detect the trace levels (ppm) to prevent contamination of the background.
Global Health Significance
A good example of a pharmaceutical quality assurance measure that has a direct impact and saves lives is EG/DEG testing. It is an essential control measure in the prevention of a familiar public health hazard. WHO contains the testing reagents in its Model List of Essential Medicines ,and international procurement agencies (such as The Global Fund) require testing on the products they buy. This not only renders EG/DEG testing a technical process but also an essential part of the global drug safety and access programs.
