As you are all aware of the global shortage of acetonitrile a few years ago, i felt it is the high time for everyone of us to look for alternate solvents like methanol or acetone for SMALL MOLECULE ANALYSIS by liquid chromatography tandem mass spectrometry to prevent such shortages ahead. Apart from methanol, acetone possibly could be a suitable alternate solvent for LC-MS/MS analysis. i have read very few articles in which they replaced acetonitrile with acetone for LARGE MOLECULE ANALYSIS by LC-MS/MS. we are planning to develop bioanalytical methods using acetone for small molecules although acetone is non-polar, which is not suitable for RP-HPLC and highly inflammable solvent (LC-MS/MS requires the application of different cone voltages) compared to acetonitrile. i would like to know whether anyone have ever tried acetone for small molecule analysis by RP-HPLC-MS/MS or just share your inputs on this.
Why do you need that ? This is the main question you need to ask yourself ?
You have an potential application that does not fit woth the use of MeOH of ACN ?
I like to use methanol or water when possible while developing LC/MS methods due to increased ionization and lower cost, but if I need to use acetonitrile, I certainly won't hesitate to do so.
Apart from the shortage of availability of Acetonitrile faced by the industry earlier, the usage of acetone is cost effective as it is economical compared to Acetonitrile. The physiochemical properties of acetonitrile and acetone are close to each other, the later one having certain advantages like the elutropic strength, vapour pressure and so on...the overall analysis run time would come down and so the cost per sample would decrease by using acetone. why not should i try to replace acetonitrile with acetone.
I think it is worth to try. I have at least seen one paper for peptide analysis where they used acetone with very good results.
Chromatographically speaking, it should work albeit with different selectivity (peak elution order) compared to acetonitrile. I don't know if acetone would affect polymeric based columns (cause them to swell), but it would work fine on silica based C18. Acetone does have a strong absorbance between ~220nm and ~300 nm (off memory) and so could interfere with UV detection- I think this would be the major issue with substituting acetone for acetonitrile.
For normal phase, acetone has a similar polarity as ethyl acetate and resides in the same selectivity group and so could be a substitute for ethyl acetate. There is a "hole" in the acetone UV absorbance allowing detection of compounds using detection at 205-210 nm, so it is useful when ethyl acetate would mask the absorbance of the desired compound.
What jack silver have written in very important and i had got point upto 95% , yes
acetone will cause swelling, also whenever acetone wash are applied other solvent wash are always need to bring back the medium in neutral conditions, but generally acetone treated samples will bring some matrix with them and which can cause in some molecules suppression effect, now it am not familiar to used acetone for general cases
Just to clarify things, my concerns about acetone swelling the packing applies only to polymeric reverse phase. Silica-bonded C18 has no such issues; I've used acetone on silica bonded C18 for non-aqueous reverse phase
I've used acetone for PTFE (Teflon) and PEEK fittings with no difficulties. Best to contact your HPLC manufacturer since the know what materials they used. You can also look up the compatibility if you have access to a Compass guide (lists solvent compatibility of a large number of plastics and metals and solvents), if you know what they use for polymers.
Here's a link to some solvent/polymer compatibility (click the polymer on the right side):
http://www.zeusinc.com/technicalservices/technicalbulletins/chemicalresistanceofpolymers.aspx
Acetone and THF are not compatible with several columns, for example polysaccharide coated columns. With ACN and MeOH you have a more widespread application.
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