How I could derivatize alkaloids working with LC/MS/MS?

[Enriqueta]

Hi,
I would like to analyse 8-dihydroxy ergotamine in plasma by LC/MS. I need to increase the LLOQ and for this reason I need to derivatize the molecule. Does anybody have experience with these kind of molecules? I do not know if there are options....
Thanks a lot for your time and help

[trozen]

it should ionize pretty well in ESI+, what's your desired LLOQ and current LLOQ? do you know your recovery and matrix effects?
I would first look into sample prep if it can be optimized

on your LC part, do you use water-ACN or water-MeOH mobile phase? any salts?
switching to water-MeOH with 0.1% formic acid and no salt alone can give you a 5x sensitivity increase

I would consider derivatization as the last resort. Theoretically, you can acetylate with acetic anhydride / pyridine; this would increase hydrophobicity of your analyte making it elute at higher % organic, which it turn would increase your signal

[Enriqueta]

Hi,
Thanks a lot for your reply. I a am working with ESI+ (Mobile Phase gradient with Water/Formic Acid 0.1, ACN/Formic Acid 0.1). Column C16. In solution the LLOQ is 150 pg/mL. In matrix will be lower.
I have to optimize the extraction (I am working in plasma) and LLE with MTBE could work. In any case, I would need to derivatize the sample. I have tried with Dansyl chloride , but it did not work. Maybe my molecule is big...
What do you think? Have you worked with similar molecules?
Thanks a lot for your help!!!