Residual Solvents by HS-GC

Chromatography Forum: GC Archives: Residual Solvents by HS-GC
Top of pagePrevious messageNext messageBottom of pageLink to this message  By Montse on Wednesday, October 24, 2001 - 02:07 am:

I am developing a HS-GC method for residual solvents (methanol, isopropanol, methylene chloride, toluene, DMF and acetic acid) in a drug substance. I have problems choosing the proper solvent for the sample: the drug is not soluble in water, it also reacts with DMSO leading to a peak (it could be dimethyl sulfide) that coelutes with isopropanol, and DMF is one of the residual solvents I'm looking for. In this case, the European Pharmacopeia recommends the use of DMI (1,3-dimethyl-2-imidazolidinone) but I have observed that it is not stable with temperature and blank peaks grow with time. Neither with DMSO nor with DMI, I cannot achieve clean blank chromatograms, because in addition to the degradation peaks, in both cases there are several small peaks in the beginning of the chromatogram that interfere with the more volatile residual solvents.
Does anybody have any suggestion?


Top of pagePrevious messageNext messageBottom of pageLink to this message  By Sunil Kumar on Thursday, October 25, 2001 - 04:34 am:

You can try the solid approach i.e.you can keep a known amount of drug substance in head space vial without adding any solvent.In a solvent the concentration of OVI gets diluted.Then for quantification, you can try the standard addition method wherein you can spike the original drug substance with known amounts of OVI at different concentration levels.Another way is to use the
total vapourization technique for the standards and do Multiple Headspace Extractions(MHE) from the same vial for standards .MHE for the drug substance is to be performed in the same way.In MHE ,the matrix effect is nullified and quantification is achieved with a high degree of accuracy.


Top of pagePrevious messageNext messageBottom of pageLink to this message  By Rodney George on Monday, November 5, 2001 - 06:00 am:

Not knowing the amounts you are trying to measure this may or may not be a good idea, but try using Dimethylacetamide as the dissolution solvent.
Quality lots of DMAc contain little or no DMF. Perhaps that is one approach. Also if your analytes and drug are stable to pH changes you may be able to select a buffer as a solvent.
DMDS or DMS can form with extended heating times from DMSO. Trying reducing the equilibration time.


Top of pagePrevious messageNext messageBottom of pageLink to this message  By Rodney George on Monday, November 5, 2001 - 06:38 am:

Not knowing the amounts you are trying to measure this may or may not be a good idea, but try using Dimethylacetamide as the dissolution solvent.
Quality lots of DMAc contain little or no DMF. Perhaps that is one approach. Also if your analytes and drug are stable to pH changes you may be able to select a buffer as a solvent.
DMDS or DMS can form with extended heating times from DMSO. Trying reducing the equilibration time.


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