Artifact Peaks Due to Minor Decomposition of Sample Diluent DMSO in Head Space-GC Analysis: Mass Spectrometric Investigation Using Deuterated DMSO and Quadrupole Time-of-Flight Mass Detection

14 June 2021, Version 1
This content is a preprint and has not undergone peer review at the time of posting.


Rationale: Head space gas chromatography (HS-GC) has become a widely used analytical technique for residual solvents determination in drug substances and drug products. During our method development of residual solvents by HS-GC for certain drug substances, four unknown peaks were observed when dimethyl sulfoxide (DMSO) was employed as sample diluent.

Methods: Use of other sample diluents replacing DMSO did not show these unknown peaks in the HS-GC analysis. HS-GC-MS was then utilized to investigate these peaks. As part of the investigation, DMSO-d6 was used to trace the origins of these unknown peaks to DMSO. A stress study of methanethiol and formic acid was carried out to provide further evidence that S-methyl methanethioate was one of the unknown peaks observed during the original HS-GC analysis.

Results: The four unknown peaks have been identified as methanethiol, dimethylsulfide, S-methyl methanethioate, and dimethyldisulfide, respectively, and it has been demonstrated that the four peaks are clearly related to DMSO through the use of its deuterated counterpart. Plausible formation mechanisms of these species are proposed.

Conclusions: The occurrence of the peaks is due to minor degradation of DMSO, facilitated by certain drug substances as analytes of the analysis. These peaks are artifacts, rather than genuine impurities of the drug substances. These artifact peaks could widely occur in HS-GC analysis, when DMSO is used as sample diluent.


Headspace GC
false positive
DMSO decomposition
stable isotope labeling

Supplementary materials

Artifact peaks of DMSO in Head Space GC analysis


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