Ethyl chloride content of an API by Headspace GC

[Graham]

We are trying to determine ethyl chloride content in an API. We have bought a standard that is 250ppm in nitrogen with the intent of purging a headspace vial with this. The API will be in a suitable solvent, say 5ml, in a headspace vial. The standard vial will have the same volume of the same solvent in the same sized headspace vial. We are struggling to relate the standard concentration of 250ppm in nitrogen to give a ppm (w/w) calculation of ethyl chloride in the solid API. Anyone got any ideas of a suitable calculation? We have several but can't agree between us which is correct!

Thanks in advance for any thoughts

[JI2002]

Convert the ppmv to mass:

mass (mg) = ppmv * MW * V/24.45

where MW is the molecular weight of the analyte,

V is the volume (in m^3) of the standard added to the headspace.

[walter]

To fall back on the advice of a professor from grad school, the only stupid questions are the ones not ask, what is an API?

[Graham]

To fall back on the advice of a professor from grad school, the only stupid questions are the ones not ask, what is an API?

Very sorry - broke my own rule of not using unexplained abbreviations! API = Active Pharmaceutical Ingredient. For the purposes of this query, = solid material.

[walter]

When we analyze solids by headspace GC we typically put about a half a gram of the solid in a 20 ml vial and add a couple of grams low vapor pressure headspace solvent such as DMF (dimethylformamide) or DMSO (dimethylsulfoxide). A response factor for the analyte is then determined by the method of standard addition. Seems to work well for us.

[krickos]

Hi

Well given that it does have a bp of like 12 degrees celsius, you might be chasing a ghost in my experiance in drug substance manufacturing. In most cases I would expect that it would go out by the process vent, but yes sometimes you need the data to prove it.
One example would be that you have ethanol in a "dry" toluene/tionylchloride reaction, in any case sampling the final dry drug substance (aka API) might be good/bad depending if the reaction of intrest is done in a appropiate temperature and the solvent of intrest may get into the crystal form of the final dryed substance. Otherwise you are better off sampling a completely filled vial of the reaction fluid,kept cooled/freezed,minimazing a loss to headspace, directly sent for analysis.

Standard addition is normally the way to go but in a normal ie USP/EP procedures QC residual solvent testing enviroment I would expect that accuracy/precison would be poor if not precations are made. So I would rather suggest going for a liquid injection with GC/MS as an in process control than on the final substance.