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DBL%20Hendrix%20small.png College chemistry, 1983

Derek Lowe The 2002 Model

Dbl%20new%20portrait%20B%26W.png After 10 years of blogging. . .

Derek Lowe, an Arkansan by birth, got his BA from Hendrix College and his PhD in organic chemistry from Duke before spending time in Germany on a Humboldt Fellowship on his post-doc. He's worked for several major pharmaceutical companies since 1989 on drug discovery projects against schizophrenia, Alzheimer's, diabetes, osteoporosis and other diseases. To contact Derek email him directly: Twitter: Dereklowe

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January 22, 2009

The Great Acetonitrile Shortage

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Posted by Derek

Now here’s a news item that I’m pretty sure you haven’t heard about unless you work in or near a laboratory. We’re in the middle of an extreme shortage of acetonitrile, a common solvent. This has been going on since back in the fall, but instead of gradually getting better, it’s been gradually getting worse: major suppliers are sending out letters like this one (PDF).

What’s the stuff good for? Well, it’s used on a manufacturing scale in some processes, so they’re in trouble for sure. Acetonitrile is a good solvent, since it’s fairly powerful at dissolving things but still reasonable low-boiling. (That’s the nitrile functional group for you; there’s nothing else quite like it). It’s no DMSO, but then again, DMSO’s boiling point is three times a lot higher, and compared to acetonitrile it pours like pancake syrup. Nobody does industrial-scale chemistry in DMSO if they can possibly help it.

Those properties mean that acetonitrile/water mixtures are ubiquitous in analytical and prep-sized chromatography systems. This is surely its most widespread use, and is causing the most widespread consternation as the shortage becomes more acute. Many people are switching to methanol/water, which usually works, but can be a bit jumpier. But that’s not always an option. Labs working under regulatory-agency controls (GLP / GMP) have a very hard time changing analytical methods without triggering a blizzard of paperwork and major delays. In many companies, it’s those people who are first in line for what acetonitrile may turn up.

So why are we going dry on the stuff? There seem to be several reasons, one of which, interestingly, is the summer Olympics. The industrial production that the Chinese government shut down to improve Beijing’s air quality seems to have included a disproportionate amount of the country’s acetonitrile production (for example). A US facility on the Gulf Coast was shut down during Hurricane Ike as well. But on top of these acute reasons, there's a secular one: yep, the global economic slowdown. A lot of acetonitrile comes as a byproduct of acrylonitrile production, which is used in a lot of industrial resins and plastics. Those go into making car parts, electronic housings, all sorts of things that are piling up in inventory and thus not being turned out at the rates of a year ago.

So taken together, there’s not much acetonitrile to be had out there. We’ve seen some glitches like this in the past, naturally, since chemical production can depend on a limited number of plants and on raw material prices. When I was an undergraduate, I remember professors complaining aboiut the price of silver reagents during the attempted Hunt brothers corner of that market, for example. But this one will definitely be near the top of the list, and it could be months before the Great Acetonitrile Drought lifts. If you've been saving some in your basement, it’s time to break it out.

Comments (109) + TrackBacks (0) | Category: Analytical Chemistry | Chemical News


1. R on January 22, 2009 9:17 AM writes...

Good post. Its shocking how the whole chemical industry can be affected by something seemingly minor and unrelated like the Olympics air quality. And also, its another impact of that rather overused phrase "the current economic climate".

Perhaps it is the incentive chemists need to move away from reliance on organic solvents, particularly in analytical chemistry, wherever possible. Nothing like a cost incentive to make people go green!

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2. Calvin on January 22, 2009 9:18 AM writes...

We've also noticed that diethyl ether is quite tricky to source at the moment. I'm not sure if that's connected to MeCN shortages. Bit of a pain really since ether sometimes purifies compounds better than other options. Oh well.

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3. Tim on January 22, 2009 9:31 AM writes...

Is this shortage going to stop production or just effect research? Will this lead to a price rise in medication?

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4. HelicalZz on January 22, 2009 9:34 AM writes...

My recollection is that we went through a similar ACN shortage in the early 90's. I was doing a lot of solid-phase oligonucleotide synthesis then, and ACN is the primary solvent for many of the reagents. Orders got quite expensive and were often delayed, as they are now. I think it only lasted for 3-6 months before supply settled down.


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5. MTK on January 22, 2009 9:49 AM writes...

While many vendors are out of acetonitrile, some still have acetonitrile with TFA added. So for those of you looking for some for HPLC purposes you might check into that.

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6. emjeff on January 22, 2009 9:53 AM writes...

Very interesting. The analytical method I used for the drug I studied in the '90s for my doctorate used acetonitrile - I went through tons of the stuff. I'd be hurting big-time if there had been a shortage...

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7. Sili on January 22, 2009 9:53 AM writes...

So did noöne see this coming at the time of the Olympics and buy up futures(?) in AcN?

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8. Sleepless in SSF on January 22, 2009 10:07 AM writes...

We do LC/MS protein analysis using ACN/water solvent systems. We actually had to break into one of three one liter bottles we have had kicking around the lab for years. Someone wrote a mid-2000 date on them, but nobody knows how long they were here before that. Fortunately, we do 75 um scale chromatography at 500 nl/min so a liter will last us a couple of months. Still, it would be nice if our pumps didn't rely on a split, since they are actually consuming ca. 150 ul/min and sending most of it to waste. I bet companies like Eksigent that make splitless nanoflow pumps are loving this.

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9. Chemjobber on January 22, 2009 10:23 AM writes...

There are ACN futures? Really?

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10. Anonymous on January 22, 2009 10:32 AM writes...

We've been having to scramble to source ACN for our analytical labs. It seems to be more unreliable than anything; we placed a big order (for us, a couple pallets is a big order)to an alternate vendor when our regular vendor told us they would be out, then the regular guy ended up having some after all.

I remember a similar problem with CCl4 in the early 90's; I was doing a radical chlorination and all of a sudden we couldn't buy it for a couple of months, and the rumor was that it wasn't going to be produced anymore. My boss ended up bringing some back that he scrounged on a company visit. Ultimatley, I did 'go green' in that I didn't use CCl4 after that, although I can't attest that the alternate was any better.

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11. CMC Guy on January 22, 2009 11:03 AM writes...

A general rule (unwritten?) in Process Development is to vet routes for potential unstable or restricted supply sources of materials as could save headaches down the road by choices of more readily available options although not always possible to control everything. Unfortunately ACN is a seemingly common solvent that does have underlying source issues as this post points out with the convergence of factors that made it worse (and hopefully temporary?). Usually there is correlation between price and security of supply and currently many proposals have had to add surcharges for the cost increase of ACN used in a production. THF and MTBE can have issues however normally not too bad for large scale work.

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12. sequiterpene on January 22, 2009 11:26 AM writes...

Calvin, Im not sure whats going on with the diethyl ether shortage. We couldnt get it back in November but luckily I got a Winchester just in time to start some Grignard reactions. Deliveries started again in January but prices from Fisher are something silly like 40 quid a bottle. Im in the UK so I dont know what the supply situation is like elsewhere- no one has really mentioned it as acetonitrile is the main concern at the moment...

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13. MTK on January 22, 2009 12:13 PM writes...


Sili may or may not have been kidding, but it wouldn't surprise me one bit if there was such a thing as acetonitrile futures. You can bet on just about anything in the financial markets.

My favorite is weather derivatives. They're evidently quite popular as risk management tools with companies whose business or costs may fluctuate depending on weather. Farmers, theme parks, heating oil companies, etc.

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14. andreew on January 22, 2009 12:30 PM writes...

Any chance of taking the waste solvent from HPLCs and rotavapping it into technical grade acetonitrile for in house use?

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15. Richard on January 22, 2009 12:59 PM writes...

Acetonitrile forms an azeotrope with water so if you tried to rotavap your HPLC waste you'd end up with acetonitrile containing at least 14 % water.

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16. Jordan on January 22, 2009 1:00 PM writes...

Great summary, Derek -- but I have to call you on this line:

It’s no DMSO, but then again, DMSO’s boiling point is three times higher

Saying that one boiling point is X times higher than another is meaningless unless its on an absolute scale. Convert the boiling points to Fahrenheit and you'll see what I mean.

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17. hibob on January 22, 2009 1:06 PM writes...

I heard a rumor about the problem back in October via VWR and decided it was worth ordering extra to last us a while. Our lab (all peptide synthesis/purification) should be OK until sometime in feb, and then we are ska-rewwed just like everyone else. The tricky problem my boss is having now is diplomacy with other PIs who want to borrow a bottle "just until our order arrives".

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18. The Inorganic Gardener on January 22, 2009 1:10 PM writes...

I have overheard "we can't get any ACN" from the mass-spec group in my department - they CAN get the 95% stuff but not the HPLC-grade they want. Obviously purifying it themselves is beyond them. Amateurs.

Andrew/Richard - is removing that last 14% water that hard? Drying agents? I have no idea - but it must be possible I would have thought?

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19. AndrewC on January 22, 2009 1:11 PM writes...

Rotovap won't work, you will need to distill it. We have thought about it here but not worth it. I am surprised that some of the solvent waste companies aren't doing this, the current price for AcN is $1000/case of 4 4L.

We tried MeOH but it just wouldn't work for our compounds and we were able to pick up enough AcN to last us a few months. Hopefully this shortage doesn't last long but the price will not go back to the pre-summer level.


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20. Derek Lowe on January 22, 2009 1:21 PM writes...

Right you are, Jordan - this occurred to me during the morning, and I've added a fix.

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21. milkshake on January 22, 2009 1:52 PM writes...

We got only one case of acetonitrile (4x4L) over the last month and half, Fisher is making all kinds of promises about delivery date then never makes good on them. Other suppliers (VWR, Aldrich, Mallinckrodt) are even more hopeless. Given that our consumption average is 20-25 cases per month, is is miraculous we lasted until a week ago but now we are out. I asked a colleague to use MeCN+methanol 1:1 mix instead of MeCN for running prep HPLC to extend our last few bottles as much as possible.

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22. Jose on January 22, 2009 2:11 PM writes...

Time to fire up a catalyst- bed filled tube furnace!

Catalytic Synthesis of Acetonitrile by Ammonolysis of Acetic Acid


The influence of principal parameters [snip] on the yield of the desired product was studied in the reaction of acetonitrile synthesis from acetic acid over g-alumina. [snip] In this work it has been demonstrated that initial temperatures of 360-380°C are optimum to effectively carry out the process of acetonitrile synthesis.

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23. Ed on January 22, 2009 3:03 PM writes...

We're using 50% MeOH, 25% THF, 25% MeCN as a substitute for 100% MeCN in HPLC applications - thus far it works just fine.

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24. KC on January 22, 2009 3:04 PM writes...

@#22 - Jose, that sounds a heck of a lot like something slavemastersVarious Academic PIs would put their underpaid workforceGraduate Students to. What good are flunkies if not for producing solvents en mass? ;)

A couple oligo mfg'rs have used the shortage as an excuse to jack around prices. I think others, still, did the same, but just didn't apologize for it.

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25. milkshake on January 22, 2009 3:44 PM writes...

I don't like using THF for prep C18 HPLC: unstabilized THF grade has lots of peroxides, the stabilized one has BHT. I dont like to have solvent-related residues in my purified stuff, TFA is often bad enough.

Generally one would like to use a water-miscible solvent with low viscosity and as good UV transparency as possible. This pretty much limits the choice.

Part of the difficulties with Fisher is related to the fact that they rejected a train-load of acetonitrile in January that did not meet the specs.

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26. nitric oxide 99 on January 22, 2009 4:29 PM writes...

I've had a lot of success in the past using isopropyl alcohol for purifying relatively hydrophobic peptides with C18 HPLC columns. Obviously your flow rate needs to be attenuated (typically to around 70% of whats normal with MeCN).

Since the shortage I've also been considering other options - I'm thinking about exploring the use of IPA/MeOH mixtures as an MeCN alternative... Anybody have any info?

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27. Fred Drinkwater on January 22, 2009 5:23 PM writes...

My old industry used to get hit by things like this. A resin factory in Malaysia (if I remember right) burned down, and basically shut down all integrated circuit packaging worldwide. An earthquake in Taiwan shutdown Taiwan Semiconductor Manufacturing Corp. (TSMC) for about 10 days - they were the #1 fabrication line for small companies and experimental parts. (And my wafers were on the line when the quake hit. They all survived; lucky me.)

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28. Don on January 22, 2009 6:06 PM writes...

Found this post through Google Alert. I work at one of only two plants in the US that purifies aceto. The only reason aceto supply is short is because the market for acrylonitrile is horrible (acrylo mainly used in cars and homes) and the plants are running at reduced production rates. Aceto production is a function of acrylo production. Make less acrylo and you make less aceto (normally).

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29. N. Pelosi on January 22, 2009 9:17 PM writes...

The shortage is George Bush's fault (and that brooding Cheney guy). Should clear up soon, since he is back in Texas.

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30. Anonymous on January 22, 2009 9:55 PM writes...

One Vendor says ..

Acetonitrile Status Update, 01/12/09
As part of our effort to keep you informed about the impact of the ongoing global Acetonitrile (ACN) supply shortage, EMD Chemicals Inc. would like to take this opportunity to provide a brief status update.

Based on the most recent trends in ACN raw material availability, and the continued low demand for Acrylonitirile (which is the core commodity of which raw material ACN is a by-product) in the plastics and fibers industries, it is expected that the shortage may continue through at least the 3rd Quarter of 2009.

In order to minimize the adverse impact of this supply shortage on our customers, we are continuing to actively investigate additional options for mitigating the effects of the shortage.

EMD Chemicals will continue to keep you informed regarding any changes in the status of the market and our ACN service levels. We appreciate your continued patience and understanding during this challenging period

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31. Lucifer on January 23, 2009 12:59 AM writes...

Pfizer and Wyeth in a tree

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32. Jose on January 23, 2009 2:47 AM writes...

WSJ says Satan is telling no lies. Sweet jesus, mary and joseph.

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33. baby bird on January 23, 2009 4:17 AM writes...

Use MeOH:
at least here it seems that pretty much all the HPLC here will work with MeOH as the organic modifier instead, of course this is no good if you are gmp glp and have chosen acetonitrile, you will have to do method development. LC-MS with APCI definately prefers Acetonitrile, ESI doesn't seem to mind either way. don't know anything much about big molecule HPLC but don't see why it won't work.

historically MeOH was used as much as acetonitrile then everyone kind of forgot about it, probably because people are lazy and just run acetonitrile gradient as the mobile, because since Uni they always have and it works just fine.

MeoH has a low viscosity compared to IPA, has a very short wavelength cut-off, doesn't collapse RP columns so frequently and is cheap.

I have bought MeOH futures

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34. Martin on January 23, 2009 8:28 AM writes...

We use acetonitrile/water for all HPLC as we do mixtures of peptidic and non-peptidic stuff. Reason we don't use MeOH is that it's not compatible with our freeze driers (at least the ones with -90 degree C traps). MeOH/water mixtures don't stay frozen. If your method lets you heat the whole wet mess on a rotavap to remove the solvent then fine, use methanol. But if you have a peptide that you want to keep cold and lyophilise and get a fluffy powder out the end, methanol ain't your friend.

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35. Sili on January 23, 2009 3:44 PM writes...

I have no idea, if there's such a thing as AcN futures. But if the Olympics had any influence on the shortage, someone should have seen it coming and tried to make a buck.

Even if it's 'only' a byproduct of acrylonitrile someone should have noticed that that there'd be a shortage when the financial downturn set in.

I'll be optimistic and hope that this does indeed lead to less waste and more recycling.

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36. frozenraisin on January 23, 2009 10:35 PM writes...

I've used MeOH instead of MeCN for some HPLC method. The main problem is the high UV cutoff for MeOH. At higher wavelengths, I didn't trust the HPLC purity anymore.

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37. Abhiram on January 25, 2009 8:48 AM writes...

Can anyone let me know how long does this crisis lasts.? What would be the price in February.? Is this the right time to stock more at this high price.?

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38. milkshake on January 25, 2009 8:51 AM writes...

I had a nice conversation with an engineer from Waters about their prep C18-column being used with methanol, and he suggested that we use thermostat heater for the column to compensate for drawbacks of replacing MeCN with MeOH: higher pressure, propensity of compounds to precipitate on the column, prolonged retention times (due to higher polarity of MeOH). He also advised us that the lifetime of heated columns will decrease as they degrade faster at higher temperatures.

For the time being we are using 1:1 MeCN+MeOH mix instead of acetonitrile, without the heating, and this mix actually does require somewhat steeper gradient (at least by 10%) to achieve comparable retention times but so far the precipitation or high pressure are not a problem

Also, Mallincrodt/Doe Ingalls gave us a valid quote until Jan 30, but they QUINTUPLED their price within two weeks since their quote and they even did not bother to tell us that we are charged $708 per case (4x4L) until after they delivered the product. This is a poorly-devised shake-down attempt, and I am afraid our Accounts Payable folks will not be pleased with such chutzpah

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39. Bruce Hamilton on January 25, 2009 1:06 PM writes...

The main reason I use acetonitrile for HPLC is that the pressure doesn't change so much during a gradient, with collateral problems.

Most HPLC books have nomographs that give equivalent solvent strengths for CH3CN:H20,
MeOH:H2O, and THF:H20 use in reverse phase mode.

The issue of selectivity can often be overcome by blends, and is covered in standard texts like "Practical HPLC Method Development " by Lloyd R. Synder and others.

I'd be pretty annoyed at opportunity pricing by a chemical supplier, and would start on the path of finding a long-term alternative supplier.

My acetonitrile supplier has rationed supplies to historical users ( setting a monthly maximum of 70%, based on last year's consumption ), and is charging near-normal prices. That means they keep my business, but it seems there are, at least, several Wall Street chemical companies around.

Bruce Hamilton

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40. Yoav on January 25, 2009 2:24 PM writes...

Well , friend of me and myself have noticed the
problem before it apear and we bought a vast quantity from China and we are now sell it in the USA and Europe.
I can tell you that most of the ACN is produced in China as it is a by-product of Acrylonitrile .
The HPLC grade how ever , is producing in the US, Europe and Israel.
And China is a vast market for it.
But, their is another thing, and this , that Acetonitrile can be produced industrially without any conection to Acrylonitrile , this has never been took place because when the product was a by-product of something else it was not economic to produce it.
Now it is and indeed we are start produce it on this February on.

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41. Kicker of Elves on January 26, 2009 10:11 AM writes...

Your english is frightening. I wouldn't buy MeCN from you. You sound like someone who would sell me water from the sink in an unlabeled bottle.

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42. Yoav on January 27, 2009 8:01 AM writes...

to number 41

If your judgment of either to buy or not from a person
Based on his spelling mistakes or dull languish .
You are in trouble and must look for a good shrink.
Anyway, I was and am not going to have a polemic with you.
Shame on you

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43. Pierrade on January 29, 2009 4:54 AM writes...

To Yoav:

I won't comment on your "languish", however I will tell you this: if I understand well you are a speculator and had a great intuition on the ACN shortage. Well done buddy! but maybe you shouldn't brag about it on a chemistry blog... you won't get much recognition from us end users, after all you are making money off of us right now!

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44. Nigel O Body on January 29, 2009 8:23 AM writes...

In the uk at least, Remsol seems to eb tryign to pool resources to recycle HPLC waste MeCN



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45. PHARMA1 on January 30, 2009 10:47 PM writes...

Changing the wash solvents and needlewash to MeOH made no difference, even when using CH3CN in both mobile phases. It's a quick way to save on solvent for now, without having to change any of the methods.

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46. ashraf on January 31, 2009 5:19 AM writes...

I agree with 45, it saves a lot of MeCN to wash with MeOH or IPA, especially that the washing step requires a high percentage of MeCN.

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47. AMIT SINGH on February 1, 2009 2:53 AM writes...

We are one of the leading manufacturers of acetonitrile hplc based out of India , we had anticipated this shortagwe and procured a lot of raw material which we are now converting into HPLC grade, we can supply the quantities out of India , kindly send your enquiries to

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48. amit singh on February 1, 2009 3:01 AM writes...

To 28, Don,

When do you anticipate that the demand for acrylo to pick up , and what abt the plant which was closed down due to hurricane , has it now started.

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49. yoav on February 3, 2009 3:16 PM writes...

to Pierrade
Respect your answere and yet, I did not not publish my E-Mail and did not try to make profit from what I was saying.
Also, I am and was not a "speculator",
I bought for my own production and sold to customers friends ( yes friends) who need it and why not?
Is it a crime to sell with a reasonable profit ?
Come on.

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50. Lorna Bankole on February 3, 2009 5:01 PM writes...

Whatever next? Will the acetonitrile shortage mean that on a worst case scenario people will be made redundant!
Please do not let this happen, we need our jobs as a lot of us have mortgages to pay!

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51. Mark W on February 4, 2009 9:26 AM writes...

It takes a shortage to focus the mind. For years solvent recyclers for HPLC have been sold on environmental grounds with little effect. Now things have changed somewhat! I hope after this that they continue to be used

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52. Steve on February 4, 2009 10:12 AM writes...

I think it is shocking, absolutely shocking that people haven't considered ACN recyclers before.

Ever since I got in to this industry I have been thinking about the environmental impacts of HPLC. I know it's not suitable for gradient elution but in my experience the bulk of the problem will be caused by those using the isocratic method.

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53. Tom Dirmyer on February 5, 2009 10:21 AM writes...

I have three containers available. Call me at 281.558.4474.

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54. Jose on February 5, 2009 12:39 PM writes...

"Ever since I got in to this industry I have been thinking about the environmental impacts of HPLC."

Eh? I think driving a car has a much larger impact?

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55. James on February 5, 2009 1:26 PM writes...

We can offer ACN regularly in quantity 50mt per month. just contact me at

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