Hello,
I've been working with methyl, ethyl and inorganic mercury compounds, trying to develop an APCI method using a mobile phase consisting of 50:50 water:methanol, containing 2-mercaptoethanol @0.01%. The instrument is an Agilent 1100, and the problem is two fold, though they are possibly linked: after an arbitrary amount of time the ion signal simply disappears. The instrument also goes out of tune after about 1 day of use in this method development work. Engineers have told me that tuning should be good for a month or so with an instrument of this type and vintage. I've generated spectra that match published data rather well, though the system as it stands is not at all robust. Any suggestions etc about what I could do to solve the two problems would be gratefully received. Thanks.

# 1 Disappearing signal: On the Agilent 1100, I've seen this happen with a dirty ion source. Next time this happens, try cleaning the atmospheric pressure side of the source if you aren't already. Use an abrasive cleaner on the parts that can handle it. A dirty source can cause a severe signal loss even when not visibly dirty. Conversely, a source can be visibly nasty and still work fine.

# 2 Going out of tune: By this, do you mean that the mass accuracy and/or resolution is failing? That could be all sorts of things. If it is simply failing due to low ion abundances, this is probably an extension of problem # 1 above.

If this is a problem that only arises when running this particular method, then I would suspect the 2-mercaptoethanol, assuming you aren't using this additive with other methods. I've never used it, but for what it's worth... A few years ago, I was looking at the effect of phosphate buffers on electrospray ionization. Of course, the nonvolatile phosphate salts cause a buildup of solid material in the ion source, and signal drops with time. A similar effect was observed with phosphoric acid, but with the acid alone I noticed buildup of a liquid film on the spray shield within the ion source, which was at ~ 350°C. Whatever it was did not appear to be volatile, nor did it crystalize into a solid upon cooling, but I never characterized it.

Anyway, I notice that 2-mercaptoethanol has a boiling point very close to that of phosphoric acid. Could the mercaptoethanol or a decomposition product thereof be coating surfaces in your MS?

Out of curiosity, why are you using the 2-mercaptoethanol?

Thanks for your input; I'll follow your suggestions re cleaning the atmospheric pressure side of the source. 2-mercaptoethanol forms compexes with mercury compounds and has been used to stop mercury sticking to injection loops, stainless steel column housings etc reducing memory effects. The complexes formed have been reported in the literature as being APCIable (Rapid Commun. Mass Spectrom. 12, 911-916 (1998)), and as our ICP-MS is down I've been trying this as a last ditched attempt. "Going out of tune" is as you mention above, with both mass accuracy and resolution not hitting the mark. I have noticed a build up of a white material on the spray heater that extends to a degree into the source. Any suggestions regarding other sulfur containing compounds with lower boiling points? Cysteine has been used in these methods, though not, to my knowledge, with APCI.

With your mass accuracy and resolution going out of spec. every day, this may or may not be related to your method. I'd suggest a service call if it continues.

You can see if your mobile phase is causing the buildup in the source, by starting with a clean source and running w/ no injections for a few hours. If you see buildup, you can probably blame the 2-mercaptoethanol. I've not used sulfur containing additives so can't recommend any. This is a tough problem. For your organic mercury analytes I would recommend switching to an acetate or formate additive, since your analytes are pre-formed cations they should ionize well without any special additive (you'd have to adjust your fragmentor etc for the M+ ions). But, I'm guessing the inorganic mercury is not going to behave well in RP-LC without a special additive.