Overcoming matrix effects: GC method development for the determination of triethylamine and dimethyl sulfoxide in a drug substance.

A direct injection gas chromatography method was developed for the determination of triethylamine and dimethyl sulfoxide (DMSO) in a drug substance (ML-189). Matrix effects were found to result in the overestimation of DMSO when methanol was used as diluent. Multiple approaches to eliminate matrix effects were unsuccessful; these included changes in sample size, split ratio, injector temperature and injector liner (e.g., deactivated liner). Ultimately, matrix effects were eliminated after the diluent was changed from methanol to acetone. A mechanism was proposed and discussed.