GC Head-space analysis (Ph.Eur. method 2.4.24)

[RaphaelDivekar]

GC Head-space analysis of Residual Solvents (Acetone, Methanol) according to BP Appendix VIII L (Ph.Eur. method 2.4.24) does not satisfy the required RSD of the Ref.solution injections (≤ 15% limit).

What may be the possible reasons for this? I hope to get a valuable solution.

[Peter Apps]

The possibilities are legion, and a hardy perennial on this forum. Try a search of the archives.

Peter

[RaphaelDivekar]

I have gone through the archieve but has not helped me solve my problem. To be specific, I am doing an GC Headspace analysis according to Ph.Eur. method 2.4.24. Solution preparations are in water as the drug substance is water soluble. Sample preparation (agitator) temperature is 80ºC for a time interval of 60 minutes. Injection volume is 1 mL and split is 1:5. Column temperature in gradient mode from 40ºC up to 240ºC and detector at 250ºC. RSD of the difference in areas of the replicate injections of reference solution and sample solution achieved is more than 15% and is not acceptable according to the requirement.I have crossed checked the sample preparation, the syringe, the liner leakage but all seems to be perfect. What may be the other reasons? I do not want to change the method as I want to avoid its validation thereafter.

[Peter Apps]

I am presuming that you have some kind of automated headspace sampler ?? If so, what type is it ?

A list of problems that have already been aired on the forum are, working from the sample prep to the detector:

Poor quantitative technique in sample prep
Loss of volatile analytes during sample prep
Leaky vials
Poor temperature control in the sampler
Interactions between sample components during equilibration
Leaks in the sampler
Blocked needles
Pressure problems
Absorbtion and adsorption in the loop and transfer line
Connection of transfer line to inlet
Split ratio
Flow rate
State of column
Detector set up and sensitivity fluctuations.

Some people do not have access to the official methods, so referring to them does not provide any information about what you are doing.

Peter

[RogerBardsley]

I would also check the split ratio as it may be placing too much water on the system causing your high %RSD for methanol and acetone. In a sense, these compounds elute with the water peak which is very broad and not "seen" by the FID. I have increased my split to 10:1 and have seen improvements in RSD for these early eluting compounds.

Best Regards,
Roger Bardsley
Headspace Applications Chemist
Teledyne Tekmar