Table 7.

Potential mechanisms for reduction of DMTS concentration in DMTS-PS80 formulations

General mechanism	Evidence for	Evidence against
Chemical degradation	No substantial evidence	Very little formation of dimethyl disulfide or dimethyl tetrasulfide over time No major chemical degradation products identified by NMR or GC-MS Addition of buffer did not stabilize formulation Stability did not change with pH
Evaporation	When outer vial is opened, DMTS smell is apparent, suggesting leaking into outer vial Some A samples, which were contained in slightly larger outer vials, contained condensate and showed larger reduction in DMTS concentration over time Some DMTS detected in headspace measurements ~2 to 5 % volume loss after 29 weeks	Large amounts of DMTS not detected in headspace measurements
Precipitation	Precipitation increased over time and with increasing temperature Large vesicle formation demonstrated in TEM images Precipitate composed of DMTS and PS80	Only a small amount of DMTS (385 ± 36 µg DMTS, N = 3) found in precipitate material
Adsorption	Some DMTS found in vial caps	Only 31 ± 2 µg DMTS (N = 3) extracted from vial caps

DMTS dimethyl trisulfide, GC-MS gas chromatography-mass spectrometry, NMR nuclear magnetic resonance, TEM transmission electron microscopy