logD and mobile phase pH
Posted: Tue May 14, 2019 7:35 am
by Rufus
I saw some articles mentioning how logD can help select the appropriate staring pH of the mobile phase.
Can someone explain, preferably on an example, how this works?
Re: logD and mobile phase pH
Posted: Tue May 14, 2019 6:36 pm
by vmu
logD can help select the appropriate staring pH
-logKa (i.e. pKa) can help select the appropriate staring pH.
For an ionizable compound, logD itself depends on pH and on pKa of the compound. The ionic form of the substance has lower logD than the neutral one. The ionic form is more weakly retained in RPLC than the neutral form.
Re: logD and mobile phase pH
Posted: Wed May 15, 2019 10:24 pm
by Rufus
OK, so what can I conclude from the pKa/logD diagram for this molecule? In terms of starting mobile phase pH,
Ibuprofen
pKa = 4.9
https://docs.chemaxon.com/display/docs/ ... n_logD.jpg
Re: logD and mobile phase pH
Posted: Thu May 16, 2019 5:33 am
by vmu
You can conclude that at pH less than about 3.9 (pH < pKa - 1) the carboxylic groups of most of the molecules (>90%) are protonated. The molecules are in a neutral form, which is more hydrophobic (larger logD) and is more strongly retained in RPLC than the negative ion (existing at high pH). You need to use the mobile phase (or its aqueous part) with pH less than 3.9 (e.g. 3.0). It is a rule of thumb to use the eluent with pH less than pKa - 1 to protonate an acid, make it more hydrophobic, and obtain good peak shape and retention in RPLC.
Note that, when choosing the mobile phase pH, you have to take into account the values of pKa of all the compounds to be separated and to think about some column-related issues (e.g. stability of the stationary phase at chosen pH).
