hello friends

[Bhargav]

Hello every body

I would like to know how to calculate the pka value of any compound (active pharmaceutical ingredient) in pharmaceutical field. And what is the effect on your analysis

please inform me in briefly.

My e-mail address is b3vd1008@yahoo.co.uk

Thanking you,

Bhargav

[pipettemonkey]

Do you wish to measure and report dissasociation constants OR, are you just looking to improve a method by adjusting mobile phase pH according to pKa's?

[pipettemonkey]

[crlar]

As Bhargav, I am also interested in knowing how to calculate the pKa of any organic compound in a easy way. It is a very important think to know in order to depelop SPE and HPLC analytical methods but usualy I don't have this information of the pharmaceutical drugs I study.
I have searched for any free software in internet but I haven't found any.
Does anybody knows how to do it?
Thank you!

[pipettemonkey]

As Bhargav, I am also interested in knowing how to calculate the pKa of any organic compound in a easy way. It is a very important think to know in order to depelop SPE and HPLC analytical methods but usualy I don't have this information of the pharmaceutical drugs I study.
I have searched for any free software in internet but I haven't found any.
Does anybody knows how to do it?
Thank you!

http://www.ap-algorithms.com/

Of all the free software I have encountered, this is the best by far. The demo has a searchable library w/ 30,000 pharmaceutical compounds. Calculates ionization, logD, solubility, as well as phys chem and bio-availability..

[Uwe Neue]

There is commercial software available from ACD, for example. How accurate do you need the information? For chromatography, it is sufficient to look at the structure of the compound and estimate: aliphatic carboxylic acid 4.5 to 5, aromatic carboxylic acid 3.5 to 4 etc.

[tom_mizukami]

What is all of the interest in CALCULATING the pKa. It seems to me that for HPLC development you just need to know the base pKa values for the common acidic and basic groups and a rough estimate of the inductive effects.

In the time it would take to input all of the parameters to calculate an inaccurtate value you could probably load an autotitrator 5 times and know the actual pKa.

[crlar]

Thank you Pipettemonkey for the web address. It looks the one I searched for.
Related to the other comments:
- Tom_mizukami, knowing the pKa of the compound I think is important to develop an SPE method of purification: if you know if the product is ionized or not at a pH, you can use "logical" values of this parameter to separate this compound from other interferences. The same in HPLC developement (a good pH of the eluent improves the shape of the peaks, the separation, etc). And what is useful to develope this is to know, not the actual pKa but the % of the ionic forms related to the pH.
- Uwe Meue: if you have a molecule with several ionizable groups, it is not so easy to know the pKa (or pKas) (that's my opinion)

Thank you all for the comments!

[pipettemonkey]

And what is useful to develope this is to know, not the actual pKa but the % of the ionic forms related to the pH.
-Thank you all for the comments!

Knowledge of % ionization as a function of pH is something that follows directly from knowlege of pKa. In other words,

% ionization = (1+ 10^pH-pKa)^-1 *100
You can't arrive at this expression without first stumbling over the pKa.

Instead, if you were referring to knowledge of distribution as a funtion of pH as being more useful than pka, I think this is mostly true for studies such as drug absorption, solubility, permeability (bbb, intestine,), where pKa-alone is insufficient. A place where the pKa is most critical would be investigating drug and molecular target interaction.

A very good value for logD can readily be determined using HPLC. However, determining pKa using HPLC isn't as trivial.

[tom jupille]

However, remember that the pKa in pure water is not the same as the pKa in your HPLC mobile phase. Even an "accurate" pKa value provides only an approximation to what will happen chromatographically.