Residual Solvent analysis in tablets

[CE Instruments]

The method I have for this is headspace however I do not have access to a headspace sampler. Can it be done as liquid injection ? Solvent extraction from the water ? If so any recommended method.

Residual MeOH, EtOH and CH2Cl2 Determination in Tablets

Detection levels needed 3 mg/10 mL of water

[chromatographer1]

What is the weight of tablets that will dissolve into water? 0.1 gram ??
or up to 2 grams per 10 mL would be nice.

If your sample weight was 0.3 grams per 10mL of water and you wanted to measure 3mg of solvent per the 10mL that would be 1% solvent by weight of tablet.

The problem would be the methylene chloride, and the methanol. Solubility limits at the temperatures you may prepare the solution and equilibria of the volatile components into the headspace of the vial are concerns that can be controlled.

I would suggest another solvent instead of water if possible. A 50/50 water - EG mono or di methyl ether or a similar mix of the like using pyridine or MEK would be a good alternative.

Keeping the methanol in the liquid solution and getting the CH2Cl2 into the solution are the issues here.

I did many years of residual solvent determinations and as long as the tablet completely dissolves and you do not have evaporation (of the analytes of interest) errors or dissolution errors the measurement can be made with great accuracy.

A porous polymer column, a "Q" type: (Hayesep Porapak or Chromsorb 102) should do very well. You should try to keep the tablet solution as dilute as possible to not foul the column. Alternately you could have a guard precolumn. Depending upon the tablet components a column should have an adequate lifetime before replacement.

I ran injector temp at 180°C and the column oven temp at 150-180°C helium 40cc/min using a 2-3m glass column 2mm ID the packings noted above for years doing this exact measurement using an Internal Std of n-Propanol or MEK. I usually kept the injection at 1µL or less if possible.

[xxx]

The method I have for this is headspace however I do not have access to a headspace sampler. Can it be done as liquid injection ? Solvent extraction from the water ? If so any recommended method.

Residual MeOH, EtOH and CH2Cl2 Determination in Tablets

Detection levels needed 3 mg/10 mL of water

SPME is another alternative,if you have access to it,with or without autosampler.