Chromatography Forum

Hello All,

with the current acetonitril shortage we are thinking about changing to a different solvent with about the same properties. To keep re-development as low as possible.
I read about MeOH + 5% IPA or THF to get the same solvent strength.

Any other ideas?

Best regards

Ace

Hello All,

with the current acetonitril shortage we are thinking about changing to a different solvent with about the same properties. To keep re-development as low as possible.
I read about MeOH + 5% IPA or THF to get the same solvent strength.

Any other ideas?

Best regards

Ace

Why bother with trying to achieve a solvent with matching strength, just adjust the %B? If you happen to be running isocratic with ACN at 25% try methanol at 35%. If a gradient, adjust your ramp or increase your initial % organic and you can (many times) reproduce the chromatography. Or simply settle for an increased RT. I try and keep things simple and avoid mixing mobile phases.

MeOH has other chromatographic properties other than ~10% less solvent strength. It can also have an effect on peak selectivity. If you just tried to adjust the %B, you may end up altering the peak elution order. I have an example of a glimepiride impurty method where the elution order for acetonitrile is A,C,F,D,E,B and for MeOH is A,C,D,B,F,E. Same method, same column, same pH, same temperature.[/img]

MeOH has other chromatographic properties other than ~10% less solvent strength. It can also have an effect on peak selectivity. If you just tried to adjust the %B, you may end up altering the peak elution order. I have an example of a glimepiride impurty method where the elution order for acetonitrile is A,C,F,D,E,B and for MeOH is A,C,D,B,F,E. Same method, same column, same pH, same temperature.[/img]

I certainly did not mean to insinuate that methanol could always be substituted for ACN. Instances such as you have mentioned with multiple components would be such a case. However, I developed and validated a method recently where prior to validation I evaluated MEOH vs ACN, 50 mm vs 100 C18 column and flow 0.2 or .25 mL/min. I settled in using a 100 mm column and a methanol mobile phase but the method would easily have run successfully with either.

Tell me, in your example, do you think that elution order of components would match that of ACN if you used a methanol mobile phase adjusted to the same solvent strength with IPA and/or THF?

[quote]Tell me, in your example, do you think that elution order of components would match that of ACN if you used a methanol mobile phase adjusted to the same solvent strength with IPA and/or THF?[/quote]

Maybe/Maybe Not.

It all depends on the polarity of the compound and the polarity of the mobile phase. There is no way to assess other than trial and error.

The following publication was written after trying to understand solvent selectivity. However, you can also read it from the aspect of avoiding major selectivity effects.

U. D. Neue, A. Méndez, “Selectivity in Reversed-Phase Separations: General Influence of Solvent Type and Mobile Phase pHâ€

I've seen a suggestion that (5:2) 1-propanol : EtOH is a good substitute for ACN. Like others have mentioned, use of the alcohol system will raise back pressure and affect selection.