Acetonitrile Shortage? If so what strategies are being adopted?

lizh

<p>In conversations with users I am hearing about the continuing shortage of acetonitrile and that it is predicted to extend through 2009. Initially at Waters, we had heard from customers that their orders would be partially filled and they might expect a reduced supply, but more recently we are hearing that orders are being drastically cut. Is this the case? </p><p></p><p>What is your company doing to alleviate the shortage and redistribute what supplies they have to critical applications?</p><p></p><p>At Waters we have discussing possible solutions. It is not easy to take a method that uses ACN to substitute methanol and expect the same selectivity, but scaling down column ID does offer a way to reduce solvent consumption dramatically without compromising the separation. With ACQUITY UPLC the use of 2.1 mm column ID's will reduce solvent usage and even existing 2.1 mm UPLC methods can be scaled to 1 mm column ID's.</p><p></p><p>There are of course implications for any method is change, however small. Are any of your Scientific Affairs personnel contacting Regulatory bodies to ask questions about similar strategies. </p><p></p><p>And what else should Waters be doing to help?</p>

ACQUITYEPM

Greetings Liz,

I realize that you are hoping for some, actual, customer commentary on this subject. My reply, merely, keeps the discussion "in the family", but this topic is also of interest to me and others in Waters R&D. The fact that, virtually, all of our Qualification protocols are acetonitrile based is generating some concern. At the moment we are only monitoring the situation, but may have to contemplate converting, or, at least demonstrating equivalency, to methanol based separations.

Which raises a question I would like to ask the Community. Would a change in solvent (ACN to MeOH) require a full re-validation of a method and assay? In theory, it should be possible (in many cases) to generate almost identical chromatography with either of the solvents. However, this would require some significant changes to the underlying parameters and conditions to achieve. I guess what I am really asking is whether changes in conditions or changes in the net results are more likely to trigger a validation effort. I'm sure this will vary from organization to organization and SOP to SOP. I also appreciate that the answer may simply be "Yes". Changes to either would mandate a re-validation. In any event, I would also like to hear from some folks who are "in the trenches" and having to struggle with this situation.

In your comment you mention some advantages offered by UPLC regarding this issue. ACQUITY also offers a "hidden" benefit that might not be, immediately, obvious. If the shortage in acetonitrile supply worsens, it may be necessary to convert some separations to methanol. Methanol/water based mobile phase systems are, typically, much more viscous than the equivalent ACN based application. Higher viscosity results in higher system backpressure. Any ACN based separation that runs in the upper third of the pressure range on a traditional HPLC system (6,000 psi), will, most likely, hit the pressure limit if converted to methanol. Isopropyl alcohol is even worse in this regard. If the same method was transferred to an ACQUITY, it would now have an additional 8 or 9 thousand psi with which to work.

Anyway, we should stop "talking amongst ourselves". I hope someone else "chimes in" on this discussion.

Regards,

pcb

MikeT

Yes well this has concerned me somewhat since hearing about this shortage. Luckily my volumes are not as high some commercial labs and I estimate we have a 6 month supply. One method (Pentobarbital) we have is backed up by a GCMS method and the other, Phosphadylglycerol, is not in production yet. But if the shortage continues for a long time that will delay offering the test.

One strategy I will be employing is recycling ACN "rinses" by filtering it with the appropriate filter device. I never saw the point in filtering before since I always used OPTIMA grade reagents for the mobile phase but now I guess I have.

Switching to MEOH would be very inconvenient. I WOULD have to revalidate methods but MEOH won't even work for Phosphadylglycerol. I've never tried it for Pentobarbital but like I said I don't want to.

regards

Mike

MikeT

Well from what I've been reading about the shortage it looks like I'm going to have to look at Methanol while I still have some ACN. As a starting point if I use an isocratic 30:70 5mM ammonium acetate (pH 10):ACN mobile phase and a 2.1 50mm BEH column what sort of gradient should I start out with using MEOH? If it matters I'm doing -ESI.

TIA

Mike

ACQUITYEPM

Greetings Mike,

Generally speaking, methanol has approximately half to two thirds the elution strength of acetonitrile (compound dependant). So, if you are running 30% ACN, I would suggest starting out around 50% methanol and see where that takes you. The same sorts of rules apply for gradients also. A final set of gradient conditions that go to 60% ACN would suggest 80% to 85% methanol. If the final conditions are 100% acetonitrile, there is nothing to do but call for 100% methanol and extend the gradient time by about a third.

Hope this helps,

pcb

lizh

Additionally, an answer from one of the Waters' chemists:

As an eluent MeOH is weaker than ACN. You can estimate the change in organic needed based on eluotropic strength.

% Methanol in Water	= % Acetonitrile in Water
10	6
20	14
30	22
40	32
50	40
60	50
70	60
80	73
90	86

I should point out that if one makes this transition they are essentially re-developing the method. The separation will change, RT, resolution, peak shape, and any other parameters you might measure are likely to change. As well, backpressure will increase, and in the case of MS, ionization efficiency could change as well (compound dependent).

Some people have found that they can use mixtures of 1:1 ACN/MeOH, 5% IPA in MeOH, 5% THF in MeOH to better mimic solvent strength. Changes in column temperature can also help as well. But always the chromatography is going to change. I would probably fall back to some good modeling software to help (Drylab etc).