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.

[1]  Shaorong Liu,et al.  A generic static headspace gas chromatography method for determination of residual solvents in drug substance. , 2010, Journal of chromatography. A.

[2]  A. Van Schepdael,et al.  Liquid paraffin as new dilution medium for the analysis of high boiling point residual solvents with static headspace-gas chromatography. , 2011, Journal of pharmaceutical and biomedical analysis.

[3]  A. M. Gillespie,et al.  RAPID CLEAN-UP OF FAT EXTRACTS FOR ORGANOPHOSPHORUS PESTICIDE RESIDUE DETERMINATION USING C18 SOLID-PHASE EXTRACTION CARTRIDGES , 1991 .

[4]  C. B'hymer,et al.  Residual Solvent Testing: A Review of Gas-Chromatographic and Alternative Techniques , 2003, Pharmaceutical Research.

[5]  M. Langhorst,et al.  Development of a headspace gas chromatography method to determine residual aliphatic amines in oligonucleotides. , 2005, Journal of chromatography. A.

[6]  A. M. Gillespie,et al.  Explanation of the matrix-induced chromatographic response enhancement of organophosphorus pesticides during open tubular column gas chromatography with splitless or hot on-column injection and flame photometric detection , 1993 .

[7]  S. Lehotay,et al.  Combination of analyte protectants to overcome matrix effects in routine GC analysis of pesticide residues in food matrixes. , 2005, Analytical chemistry.

[8]  B. Kersten.  Drug matrix effect on the determination of residual solvents in bulk pharmaceuticals by wide-bore capillary gas chromatography. , 1992, Journal of chromatographic science.

[9]  Jayalakshmi Somuramasami,et al.  Static headspace gas chromatographic method for the determination of low and high boiling residual solvents in Betamethasone valerate. , 2011, Journal of pharmaceutical and biomedical analysis.

[10]  Huiyuan Yao,et al.  Determination of 266 pesticide residues in apple juice by matrix solid-phase dispersion and gas chromatography-mass selective detection. , 2005, Journal of chromatography. A.

[11]  E. Doelker,et al.  Residual solvents in pharmaceutical products: acceptable limits, influences on physicochemical properties, analytical methods and documented values , 1997 .

[12]  Juliane Jung.  Gas Chromatographic Headspace Analysis , 2016 .

[13]  F. Lanças,et al.  Matrix effects observed during pesticides residue analysis in fruits by GC. , 2009, Journal of separation science.

[14]  Jitka Zrostlíková,et al.  Matrix effects in (ultra)trace analysis of pesticide residues in food and biotic matrices. , 2003, Journal of chromatography. A.