by
krickos » Thu Sep 30, 2010 4:59 pm
Well first I would smack the chemist on the head for not being aware of the basic principles of residual solvent testing
Seriously I am only partly joking, cause such a choice of dissolution solvents may mask the residual solvents of intrest. In other words the chemist might have put you in trouble.
Possible quick and dirty approach:
First check a standard with said dissolution solvents + tert-butanol to check resolution.
Dissolve 0,1g of API in said solvents to 25ml.
Due to unknown water content inject 0,5µl with a 5ul syringe on a GC, injection temperature 250°C using a liner with glass wool (might need changing after each sample injection, and hope API stays in wool and do not degrade into interfering peaks).
Split ratio: start in area of 1:20-1:50
Column oven start at 40°C for 4-5 mins then increas oven temp 10°C/min up to max temp for column.
Columns typically like DB-1, DB-WAX,DB-624 may be used, column manufactures like Agilent keep a retention order index for residual solvents for those columns in their catalouges.
Doing it more properly (direct injection may work but headspace injection is more common):
a. Chose a different/less interfering dissolution solvent, ie DMF, DMSO or even water might work given the information (even CS2 can be considerd for direct injections). As headpsace is typicallly used solubility in room temp is not necessary as long as dissolution is obtain in headspace oven 40-80°C(ie sample directly weighed into vial).
b. Check USP chapter <467> or Ph Eur chapter 2.4.28 for screening methods. Chapter 5.4 Ph Eur and ICH Q3C guideline provides additional general info on residual solvent testing. These screening/limit test methods are based on the WAX/624 type columns.
Again, smack the chemist
, just to be clear, my slight annoyance is not aimed at Rob, I have spent considerble time and effort to understand my costoumers need and likewise explained our reality for them (ie we are not a CSI program on TV even though we can do magic at times
)
