Hi all,

Because of the specific nature of the project I am working on, I have to use 100% MTBE(methyl tertiary-butyl ether) or 100% Ethyl Acetate or combined MTBE/Ethyl acetate as the mobile phase for LC-MS/MS analysis of small molecules, which consequently push me to normal phase LC-MS field. I am using a Zorbax SB-CN 2.1 x 50mm column, flow rate 300ul/min, ESI-MS/MS on a TSQ Quantum instrment. My problem is that I have unstable spray and the signal intensity is low. I don't care separation too much, but I want to improve the signal stability and the sensitivity under 100% MTBE or 100% ethyl acetate as the mobile phase. IF you have any experience in normal phase LC-MS or LC-MS using such pure organic solvent as above, can you share with me your experience? I guess APCI probably will work better than ESI....What other ways to improve the signal stability and sensitivity?

thanks!

Typically, you should use APCI when doing normal LC/MS/MS, not ESI since your sample will be non-polar, correct? Switch to APCI and most of your problems will go away.

Good luck.

I have never done it, but have seen some threads on sci.techniques.mass-spec. Here are a couple of threads on Google Groups:

http://groups.google.com/groups?hl=en&lr=&ie=UTF-8&safe=off&threadm=6lc1ht%24er4%40acmey.gatech.edu&rnum=3&prev=/groups%3Fq%3Dnormal%2Bphase%2BLC-MS%26hl%3Den%26lr%3D%26safe%3Doff%26btnG%3DGoogle%2BSearch%26site%3Dgroups

http://groups.google.com/groups?hl=en&lr=&ie=UTF-8&safe=off&threadm=a8b5q1%24ka5%241%40news-int.gatech.edu&rnum=1&prev=/groups%3Fq%3Dnormal%2Bphase%2BLC-MS%26hl%3Den%26lr%3D%26safe%3Doff%26btnG%3DGoogle%2BSearch%26site%3Dgroups

or just go to groups.google.com and search for it.