Sample analysis resolution vs standard resolution

[megz7169]

Hi there,

I'm trying to perform residual solvents testing of radiopharmaceuticals via GC-FID. When I inject my mixed standard containing Ethanol and Acetonitrile in water, there is some peak tailing being seen in the Ethanol peak.

When I perform injection of the sample, the peaks attributed to Ethanol and Acetonitrile are very poorly resolved (pretty much merging into another) and the Acetnoitrile peak is showing double humps. The sample is based on a NaCl matrix.

My current method parameters are based on a 30 x 0.53 x 3mm column, on N2 carrier gas (due to cost rises and availability of He), with a 250deg C FID and a 150deg C injection port. The column oven is isothermal at 40degC and the injection volume is 1uL.

Ive tried changing the liner,o-ring and septa to no avail.

Can anyone advise of any other steps I can take to try and mitigate the above sample issue? Im restricted by method stipulations in the Marketing Authorisation as per the below, but any guidance/recommendations would be appreciated!!!


Column: 30m x 0.53/0.32 x 1-3
Column stationary phase: Fused silica capillary column coated with cross-linked 6% of polycyanopropylphenylsiloxane and 94% polydimethylsilloxane.
Injector temperature: 150 - 250deg C
Injector volume: >=1ul
Oven pressure: 0.1 - 8bar
Flow rate: 1-15ml/min
Split ration: 5 (may be adjusted provided satisfactory detection)
FID temperature: 200-300degC

[James_Ball]

Is the standard prepared in the same concentration NaCl as the samples contain?

[megz7169]

Hi James,

The standard at present is prepared in water, not NaCl

[Consumer Products Guy]

First of all: 1ul is a huge injection for an aqueous matrix. I'd go to 0.5ul as a start.

Also, we assayed for ethanol in hand sanitizers using ACN as the internal standard, based on a USP method (have no idea why USP did not use 1-propanol as internal standard, but that's another story, and my supervisor wanted us to sty close to the USP procedure to speed our validation). And we had no problems with peak shape or resolution.

So try the 0.5ul injection size first, from a 1ul syringe.

[megz7169]

Thanks for your input!

I’m afraid the marketing authorisation I’m working to limits me to injection size >=1ul.

I’ll try a 0.5ul injection and if this resolves the issue I can see if a variation to the MA can be made.

Thanks

[James_Ball]

The matrix of the standard should match the matrix of the sample, or you can see differences in response and chromatography sometimes. If only the samples give problems, then try a matrix matched standard and see if the problem is present in that, to make certain it isn't the matrix causing the problem.