Mobile Phase Expiry

[i79]

I work in a lab conducting LC-MS/MS. Mostly our work is reverse phase. We use a wide variety of mobile phases and columns, but nothing out of the ordinary.

Can someone give me an idea as to what expiry prepared mobile phases usually have in indusrty? Our SOP's state 1 week for all mobile phases regardless of organic / aqueous composition / buffer content / pH. We rarely notice and changes in RT due to evaporation of volatiles and bacterial growth appears to be rare. Are we being too conservative?

Thanks in advance

[Albany-12303]

Our lab gives an expiry date of 1 week unless otherwise specified.

I have found that mobile phases containing THF only last a couple days (because of the generation of peroxides that affect the baseline stability).

I am working now with a mobile phase that contains about 10g/L phosphate buffer (not my choice, but it is based on a USP method). It is a gradient method with a mixture of 98:2 buffer:acetonitrile in MP A and 78:22 buffer:Acetonitrile in MP B. I found that MP B is stable for at least a week while MP A is only good for 1 day (after which the baseline is unacceptable). I attribute this to algae growth in MP A, and I suppose that the 22% organic in MP B is enough to retard this.

I just checked a flasks of MP A and B that I left on my bench and have not discarded yet. MP A is cloudy while MP B remains clear.

[John]

We give ours 3 months. I don't think composition varies significantly due to evaporation as long as the MP is capped. I have seen no bacterial growth in MP of 15% organic upwards in 3 months storage. Of course these remain stored in the dark for most of that time. We see some nastiness growing in our injector rinse solutions, which are 5 % MeOH and sit on top of the LCs, in a few weeks.
We don't run LCMS though. I would imagine that MS would detect problems way more easily than the human eye.
For varying longevity with organic concentration, I use the following guide:
Beer 5% - good the next day
Wine 12% - good for a few days
Port 20% - few months
Gin 40% - Years

This is the second time in a week that I have used a drinks analogy in an LC forum. I may have a problem.

[Bruce Hamilton]

The expiry is usually decided during method development. If you use high quality water and have very little organic present in your mobile phases, their expiry is likely to be related to wildlife growing ( weeks ), and/or absorption of CO2 and other gases - which may affect unbuffered systems and/or UV characteristics.

If you have lots of organic present ( 10%+ ) then most mobile phases will last weeks to months - provided they are sealed and stored OK ( eg to prevent loss of volatiles ). Some organics ( eg ethers, acids ) can degrade or react, as will some buffers, and should be replaced more frequently. Many standard methods define the expiry.

Regardless of the lab rules, an auditor would want to see how you established the expiry date for all novel mobile phases. The easy solution is retain some old mobile phases during development/qualification and analyse samples with them and fresh mobile phase after several intervals. You may be surprised how long you can use many mobile phases.

HPLC grades of some ion pair reagents are fairly expensive, so making up just sufficient for your daily needs is a good idea, as work schedules can change.

Please keep having fun.

Bruce Hamilton

[HW Mueller]

This has been discussed extensively, recently, and, and...
i 79,
One more thing though: If your solution shows signs of microbe growth after one day it should give rise to the concern that somewhere you have massive amounts of bugs, enjouying life, where they shouldn´t be. Did you ever check the UV of your water against some other source of water?

[DR]

We get 1 month, although I've seen some that are quite good after 6 and others that go south faster than 1 month.

THF peroxide formation rates are actually slower in your MP than they are in the stock bottle (though it helps to keep things N or He sparged and in the dark).

If you have bugs in your phosphate, you had better make sure that there aren't any in your LC!

I suspect that the atmosphere, light and stuff entering MP jugs are responsible for more MP deterioration than bugs and TFA degradation (high PO4/low organic combos excepted).

[i79]

Not getting anywhere with lobbying for a bit of common sense on this issue. My managers seem to want to slap a generic one size fits all solution on the problem rather than allowing us Analysts to use some thought. Never mind, it's their cash that they are throwing away every week....

[Albany-12303]

We work in a tightly controlled GMP environment, and it is inconcievable (OK its a bit of a strong word) that we would use a mobile phase months after preparation.

Our SOP's state that all mobile phases must be given a 2 week expiry. I assume that this is normal across the pharmaceutical industry (or at least anyone that comes under the auspices of the FDA).

Even our solid chemicals, such as Sodium Chloride, are given a 5 year expiry date (even though many would be OK after millenia.

As far as my 'unstable' mobile phase goes (a heavy phosphate buffer, pH 7.1), I use bottled HPLC water to make it. I think that if my method was isocratic, it would be OK for a few days, but gradient methods tend to amplify any problems associated with MP stability.

[Peps]

A comment on the previous post. I also work in a pharmaceutical laboratory under GMP control and we have expiry dates for up to 3 months for our mobile phases depending on the organic content. What I want to say is that I don't believe that these long expiry dates interfere with GMP since you must always fulfil the (more or less) strict criteria set for the system suitability test... After all, what you want is for your system to perform identically from time to time...

/Peps

[HW Mueller]

Albany-..., but it´s conceivable that you use your stuff, short of two weeks, even if crud is in it?
Are these straight jackets created to do chemist´s work with cheap labor?

[Kostas Petritis]

In our lab the decision of mobile phase expiry is left to the researchers... For us it is more of a problem how much we are allowed to keep our mobile phase waste around (i.e. 90 days of max waste accumulation) than the mobile phase in our HPLC's.

Having said that, in general we are trying to avoid keeping highly aqueous solutions for too much... Another solvent that we are not keeping more than a month is 100% ACN with acid into it (i.e. TFA or formic acid...) due to the tendancy of ACN to polymerize and be insoluble in ACN...

[rc_12321]

In fact ,this is some what shocking .I do not think mobile phases can be stored for months together.Thay may not pose big problem in case of single peak analysis ,but when you are using it for related substances analysis , where in number of peaks ( prabably some of them are ph sensitive) are more, it is not practically good to use those mobile phases which has been stored for months together.

[Kostas Petritis]

What do you mean by "mobile phase can not be stored for months together"? Mobile phases with high organic solvent content are mainly stored either in the flamable cabinet while high aqueous it depends... they might be in the refrigerator or just the bench... As I also said depending on the mobile phase composition the expiry date might be different... so what exactly do you mean?

[Sunjay]

We are preparing the mobile phase sufficient for the required sample analysis. In this way we can tackele the problem of wastage and also giving expiry dates???

Generally we are using the mobile phase upto one monthe with organic content and 15 days without solvents, unless there is no precipitation.
Moreover, we have mentioned in our SOP that stored mobile phases shall only be used if ststem suitability passes.

But it is good practice if we prepare them for one time use only.

Regards

[HW Mueller]

Is it out of fashion to run standards regularily and often inbetween analyses? Certainly that will show whether the mobile phase is deteriorating. It has been mentioned many times: The lifetimes depend on a lot of complicated factors, one very important one is cleanliness. If you regulate this than you end up putting lifetimes on these solutions which are dictated by the worst slob in the business, etc.