J. Cosmet. Sci., 61, 225–234 (May/June 2010) 225 Simplifi ed assay of diethylene glycol and ethylene glycol in various raw materials by capillary gas chromatography K. MOLEVER, Research and Development Department, The Dial Corporation, a Henkel company, 19001 N. Scottsdale Road, Scottsdale, AZ 85255. Accepted for publication November 16, 2009. Synopsis The FDA has recently taken steps to reduce risks due to raw materials affected by economically motivated adulteration (EMA). One area of great interest is diethylene glycol (DEG) or ethylene glycol (EG) adultera- tion of glycerin, propylene glycol, and solutions of sorbitol, for which the USP monographs have recently been revised (1). Such adulterations have occurred many times and in many countries, including a tragic episode between November 2008 and January 2009 in which 84 children in Nigeria died after ingesting teething syrup contaminated with DEG (9,10). To eliminate this problem, the FDA has required manufac- turers of fi nished products to assay and confi rm that incoming glycerin, propylene glycol, and sorbitol solu- tions meet the USP limits, and the FDA/USP has incorporated such testing into the identity requirements of its updated monographs. Unfortunately, even though USP test procedures detail a simultaneous DEG and EG assay for these materials, different standard solutions are specifi ed depending upon whether the incoming sample is glycerin, propyl- ene glycol, or a sorbitol solution in addition, a certain gas chromatography (GC) capillary phase is detailed for sorbitol solutions, while the assays for glycerin and propylene glycol use a different capillary phase, requir- ing column changeovers, separate GC systems, or front/rear column confi guration. In addition, NF mono- graphs for polyethylene glycols (PEG) and polyethylene glycol monomethyl ethers (MPEG) used in pharmaceutical products also require DEG and EG testing (detailing their own specifi c tests) three separate test procedures for these types of raw materials (the larger PEG-type polymers are assayed differently than their smaller counterparts), making assay at QC unwieldy. This paper describes a single, simple test procedure that is applicable to the simultaneous assay of DEG and EG in all types of the described raw materials, using one standard solution. The assay procedure involves straightforward isolation, trimethylsilylation, and simultaneous capillary gas chromatographic quantitation using capillary GC with fl ame ionization detection. Although the USP-NF limits are 0.10% DEG and 0.10% EG (and 0.25% total DEG plus EG for the PEG and MPEG products), in reality any EMA would be at levels signifi cantly higher than that, as low-level illegal EMA would not be economically advantageous. The scope of this project was not to fully validate this technique for inclusion in USP-NF, but just to dem- onstrate its applicability for those wishing to utilize it or take it further. INTRODUCTION The FDA has become more concerned about raw materials affected by economically mo- tivated adulteration (EMA)—willfully adulterating more expensive desired material by adding less expensive material. Many times, this adulteration is done using signifi cant scientifi c understanding, to produce adulterated material that passes most quality checks.

JOURNAL OF COSMETIC SCIENCE 226 This is problematic because such adulterated materials can present serious public health risks and consequences. Recent examples of EMA that resulted in deaths include the 2008 adulteration of milk and infant products with melamine (12), and the diethylene glycol adulteration of glycerin (Nigeria 2008–2009, Panama 2006, India 1998, and Haiti 1995) (9,10), which will be addressed here. In response to this, the FDA requested that the USP incorporate into the identity section of its glycerin monograph the require- ment for fi nished product manufacturers to assay and confi rm that DEG and EG meet the limit maximum of 0.10% (each) this updated glycerin monograph became offi cial in May 2009. In addition, the FDA/USP has incorporated similar DEG and EG require- ments into its updated monographs for propylene glycol and for sorbitol solutions, effective February 2010 (2,3). The monographs for these three materials detail a simul- taneous DEG and EG assay, but require different standard solutions depending upon whether the incoming sample is glycerin, propylene glycol, or a sorbitol solution. In addition, monograph GC tests for the DEG and EG in glycerin and propylene glycol use a G43 stationary phase while the test for sorbitol solutions details a G46 stationary phase. Polyethylene glycols (PEG) and polyethylene glycol monomethyl ethers (MPEG) have a USP-NF maximum level of 0.25% for the combination of DEG and EG their USP-NF test procedures utilize older technology, packed-column gas chromatography (GC). Higher-molecular-weight samples of PEG and MPEG require unwieldy, time- consuming vacuum distillation followed by separation and colorimetric quantitation of the total of DEG and EG (1). Current offi cial USP-NF test procedures (1) for these polyol-type materials detail: (1) Capillary GC using phase G43 for glycerin samples and propylene glycol samples (2) Capillary GC using phase G46 for sorbitol solutions (3) Packed-column GC using phase G13 for PEG samples with nominal molecular weight less than 450, with quantitation done by peak height (4) Packed-column GC using support S2 for MPEG samples with nominal molecular weight less than 600, with quantitation done by peak height (5) Complex vacuum distillation followed by colorimetric total assay for PEG sam- ples with nominal molecular weight 450 or above, but not more than 1000, and MPEG samples with nominal molecular weight 600 or above but not more than 1500 The FDA states that “a manufacturer may use an equivalent identifi cation procedure that includes a test to detect and quantify DEG provided it meets the relevant safety limit.” (3). Advances in capillary gas chromatography have greatly enhanced capabilities for re- solving complex mixtures frequently, the resolving capacity of capillary columns can eliminate the need for extensive sample preparations or cleanups. In reality, any EMA with DEG or EG would occur at levels much higher than the USP-NF limits, and so any test procedure that could simply determine levels at the USP-NF limits or higher should be able to be utilized if documented. Since the author had expertise (including publica- tions) for components similar to DEG and EG, and with matrices such as these, it was logical for this to be investigated using modern techniques. The sought-for analytes and the sample components themselves were reacted with BSTFA trimethylsilyl derivatizing agent, then taken for capillary GC analysis. The sample preparation is straightforward and requires approximately fi ve minutes, and GC quantitation is completely automated, including calculations of the DEG and EG levels.