Itraconazole precursor ion

[konkous]

Hi to all,

I'm currently developing a method for the quantitative determination of itraconazole and its hydroxy-metabolite in human plasma. During the tuning procedure of the mass spectrometer i performed a Q1 scan in order to see my compounds. I noticed that the most abundant m/z was equal to 705 and i noticed the isotopic pattern of the chlorine atoms. The molecular weight of itraconazole according to the RX list is 705.64. Can anyone explain the reason why i don't get a m/z equal to 706.64 in ESI + mode but a m/z equal to the molecular weight of my compound?

[Kostas Petritis]

At the beginning I wanted to say that your calibration is probably off but according to this article : http://medicine.iupui.edu/clinical/Itroconazole.pdf they also observe the itraconazole at m/z 705 and I confirmed that it's MW is the one that you mentioned. So at this point I do not know why exactly but it seems that what you see it is correct.

In general you can observe such a thing if your molecule is already charged by itself (i.e. if it contains a tetrabonded nitrogen). At this case, you can observed the M+ and not M+H+ in electrospray ionization. Looking at the chemical structure though I didn't see such a case (although I didn't look very carefully...).

[MG]

The 705.64 is the average molecular weight. Chemfinder lists the molecular formula of Itraconazole (CAS# 84625-61-6) as C35H38Cl2N8O4, which calculates to a monoisotopic molecular weight of 704. Thus, your observation of 705 seems to be an ordinary M+H ion. The chlorines are causing the average mw to be significantly higher than the monoisotopic mw in this case.

Without having to calculate, another clue is the number of nitrogens. Under the nitrogen rule, the neutral molecule* should have an even molecular weight because it has an even number of nitrogens.

*[as should the odd-electron M+ ion, but that doesn't matter here]

[konkous]

Thank you very much sir, you have been most helpful. You are absolutely right, i really appreciate it.