Hi All,

I have been experimenting a bit with chemicalize and have not found the LogP, LogD, and pKa results to be as consistent with literature reported experimental results as I had hoped. I suppose the values at least put me in the right neighborhood to better plan my approach for HPLC method development. However, if I were to take the LogD data from chemicalize at face value in the example below, I would assume that the compound could not be adequately retained using buffers with pH below 7.4. However, the USP monograph method uses buffer at pH 3.0 (35:15:50 MeOH:ACN:Buffer). So, I would be way off base!!

Is there a rule of thumb as to how much error is associated with these values from chemicalize? When interpreting LogD results from chemicalize, what value of LogD would you consider to be too low to make RPLC at that pH an option? Or, is it not safe at all to make that assumption based on the predicted values? Based on my own assessment across several compounds, I think I would only discard the possibility of RPLC at a specific pH with a LogD of -1.75. At that point, I may consider HILIC or adjusting the pH.

Below is a specific example for Amlodipine:

Chemicalize Results:
Strongest pKa = 9.43 (only two microspecies)
LogP = 1.64
LogD at pH 1.7 = -1.40
LogD at pH 4.6 = -1.39
LogD at pH 7.4 = -0.37

Literature:
pka = 8.6
LogP = 3.00, 2.96, and 3.17
LogD at pH 7.4 = 1.41 and 1.11

Would be interested to hear from others as to how useful you find these calculators.

Thanks in advance for your thoughts!