title: Analysis and stability of the candidate sulfur mustard decontaminant S-330.
abstract: The chloroamide compound 1,3,4,6-tetrachloro-7,8-diphenyl-2, 5-diiminoglycoluril (S-330) was found to be a strong reactant in dermal formulations for the decontamination of sulfur mustard (HD). In this report, we present analytical methodologies applicable to the characterization, purity determination and quantitation of S-330 in bulk material or formulations. High-performance liquid chromatography-mass spectrometry (LC-MS) coupled with atmospheric pressure chemical ionization (APCI) interface or ultraviolet detector and nuclear magnetic spectroscopy (NMR) were used to identify and characterize S-330 and impurities in the synthetic lots or degradation products in formulations. Bulk synthesis using a chlorination process has yielded a product of 90% purity. The major impurity has been separated and identified structurally as the trichloro analog of S-330. Higher purity S-330 can be made using column chromatography, but this does not appear to be economical for large-scale production. Factors affecting the stability of S-330 in topical formulations include water content, pH, alcohols and UV light. Chloroamide S-330 decomposes at 50-60 degrees C and is not amenable for GC analysis. The HPLC technique is superior to NMR or active chlorine assay in the purity determination for S-330 in bulk material or formulations. In topical formulations containing S-330, 5-10% of water can be tolerated, but alcohols and acidic and basic conditions should be avoided.
authors.affiliation: U.S. Army Medical Research Institute of Chemical Defense, APG, MD 21010, USA.
authors.forename: M L
authors.initials: ML
authors.lastname: Shih
authors.forename: W D
authors.initials: WD
authors.lastname: Korte
authors.forename: J R
authors.initials: JR
authors.lastname: Smith
authors.forename: L L
authors.initials: LL
authors.lastname: Szafraniec
mesh_terms: D000577:Amides / Q000032:analysis* / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid; D004355:Drug Stability; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D009151:Mustard Gas / Q000378:metabolism*; D020011:Protective Agents / Q000032:analysis* / Q000737:chemistry; D012867:Skin / Q000187:drug effects*
chemical_list: D000577:Amides; D020011:Protective Agents; C405262:chloroamide S-330; D009151:Mustard Gas