Analysis and stability of the candidate sulfur mustard decontaminant S-330

• Published in: Journal of applied toxicology 1999-12, Vol.19 (S1), p.S89-S95
• Main Authors: Shih, Ming L., Korte, William D., Smith, J. Richard, Szafraniec, Linda L.
• Format: Article
• Language: English
• Subjects: Amides - analysis; Amides - chemistry; chloroamide; Chromatography, High Pressure Liquid; decontaminant; Drug Stability; glycoluril; LC-MS; Magnetic Resonance Spectroscopy; Mass Spectrometry; Mustard Gas - metabolism; Protective Agents - analysis; Protective Agents - chemistry; reactive topical skin protectant; S-330; Skin - drug effects; sulfur mustard
• ISSN: 0260-437X; 1099-1263
• DOI: 10.1002/(SICI)1099-1263(199912)19:1+3.0.CO;2-V

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°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.