Chromatography Forum

Good day,

I am in the process of transferring a drug product, residual solvent, GC-HS method into our laboratory and have observed several shortcomings. We run residual solvents daily with an in-house developed method which is quite different (diluent:DMAC/column:624) from the one in question. This client supplied method is relatively new to our team and we continue to uncover potential problems.

Problem statement: A large "hump" is eluting prior to the DMSO (solvent peak).

Method details:
Sample & Std diluent: DMSO
Column: DB-1, 30m x 0.32mm x 5µm
Oven program: 60°C (0 min hold), 5°C/min to 100°C (0 min hold), 20°C/min to 180°C (0 min hold), 50°C/min to 250°C (2.6 min hold)
HS oven: 150°C
HS loop: 180°C
HS transfer line: 190°C
Split ratio: 2:1

Observations: A mostly stable baseline is observed upon the first injection of the day, subsequent injections present abnormal baseline immediately prior to DMSO peak. This irregularity, or "hump", is observed consistently throughout the remaining injections with comparable magnitude/shape. At times significant "junk" is eluting after the DMSO peak, this is seen occasionally at no regular interval on longer sequences. Please see below for representative chromatography.

Hypothesis: Polarity differences between column and DMSO are adversely affecting stationary phase retention/peak shape of DMSO.

Please let me know if I can provide any further information. Any insight into the cause and potential remedy to this problem is greatly appreciated!

Thank you, kindly, in advance!

Cheers,
Jeremy

Possibilities for problems are abundant. DMSO is quite 'sticky' and is liable to undergo reactions with many common matrix components.

This could be a residual DMSO eluting from the sample loop/transfer line/injection port/head of column contamination which might be retaining and releasing the DMSO slowly, continuously, as the vapor is partially retained and released. Any metal contact is especially dangerous.

A thorough cleaning and replacement of hardware can be a good thing to execute to determine if it might make an effect upon your problem.

I have preferred to avoid DMSO and use DMAc or DMF if possible.

good luck,

Rod

Do any of the target analytes elute at the same time as the hump ? If not I doubt that it will have any impact on results.

Peter

Rod and Peter,

Thank you for your replies to my questions.

Due to multiple reasons we will actually have the opportunity to develop a new method for this particular analysis. Will be looking to DMAC as a first choice on a 624 phase column, which is what we typically are running for residual solvents.

Thanks again!
Jeremy