We are doing analysis of glimeperide using lc/ms/ms, at m/z 491>352 and 494>369, using 10mM ammonium acetate and ACN (25/75). We are getting interference at both m/z while running blank plasma, with ether extraction. We also tried as, Salem I I et al. and also thought about contamination, thus cleaned thoroughly. But still getting problem. Does any one have experience of this problem or did glimeperide analysis in lc/ms/ms? Please suggest me to overcome this problem. Waiting for response

What column are you using?

I am using C18 (2.1X100mm, 3micrometer).

I am still trying with other mobile phase. Is the poor solubility of drug can contribute this problem? I mean after each analyis there may be some remaing drug particle intrapped in the column. What is your views on glimepiride?

Can I use DMSO (Dimethysulfoxide) in low concentration in the mobile phase? As the glimepiride is highly soluble in it, but poorly soluble in ACN, Methenol and water. I hope some one could guide me.

I doubt solubility is the problem. Since you are using a triple-quad, I assume you are working at ng/mL or lower concentrations. (Though I have no specific knowledge of your analyte). I have experienced this problem plenty of times with biological matrices. It is quite possible that you have an endogenous compound with the same parent and daughter ions as your drug, that also happens to coelute. If available, you could try a different daughter ion and see if the interference disappears. Otherwise, you have to change your chromatography to separate the interferent from your drug.

It could also be autosampler carryover. To check this, run a solvent blank immediately after running a high level spike or standard. If you haven't already, you should probably check for carryover before assuming it's something else.

Thank you MG, I am also thinking in this line. I found little carryover, so I am willing to use DMSO in mobile phase and wash solvent too. As the analyte is highly soluble in it, it may decrease the chances of carryover( I found decrease interference while using DMSO in wash solvent). I am still confused to use it in Mobile phase.It will damage my column or not?
Regarding the similar endogenous parent and daughter ions, it may be. I would like to include here, the interference is high in one m/z (491>352), than other. I will try with other daughter ions. But one more important thing, I am getting similar (but less) problem with distilled water (extracter in the same manner. ( I am using diethyl ether for extraction). I will add more after trying all process once again. But in the mean time, if you find anything special please add here.
Waiting for comment.

Regarding DMSO, I'm not sure how that would behave as a mobile phase additive. I guess it would be a very strong eluting solvent. It might also dissolve any polymeric tubing or injection valve seals in your system. I've never heard of anyone using it in their mobile phase, so can't recommend it. As a needle wash, it might be okay depending on your autosampler configuration, and whether the wash solvent would contact any seals or tubing incompatible with DMSO.

But, I am not sure if flushing things with DMSO will fix your problem. You said you found little carryover, so I assume that is not your problem. You said you see the interferent in blank water extracts. What happens if you take that same distilled water and inject it without extraction? What about injecting an aliquot of your mobile phase? The answers to these will help diagnose the problem. I assume from your original post that this is an isocratic LC method. If it's a gradient instead, try also running the gradient with no injection.

Dear friends
sorry for being late!
I solved the problem. Specially thankful to mr MG. It was major problem of tube materials. I was surprized by it. Finally I used falcon tubes. I also changed the extraction solvent using mixture of diethyl ether and dicloro methane.
I did not use DMSO. I successfully analyzed samples from bioequivalence study.
I need some help on FDA format for validation of study. If any body has it please send me. Preferebly in excel format.

i am developing method for prep isolation of one of glimepiride impurity from its bulk drug.i got good separation in a (acidic water:acn) mobile phase. but problem is that for prep i require sample conc of 50-100mg/ml and it is not dessolving in the mobile phase.should i use some quantity of DMSO in my dilunt.
i will be thankful if someone can guide me.

Solubility is a common problem in preparative chromatography. However, there are ways to get around it. We have developed the method of at-column dilution to get around this problem. Please look at our article in Chromatographia Supplement Vol 57 (2003), S121-S127.