Hi,

When you are about to develop a method, you usually use pH to control the retention, in the litarature you find many things about this.

So my question is the following: How do I see if a product is a basic component, or acid, or neutral?

And another question: How do I find the pKa values from my components? Are there some databases on the web, or can I find this value by some experiments?

Thanx to all.

not for neutral samples.

I have the same question at the moment: What happen if you have a drug which has a pKa of 7.03? Do you treat it as an acid or a base? My colleague said althought it is very weakly acidic, but since it is an amine (has a nitrogen group), so I should treat it as a base. Is it true? Do I differentiate if a drug is an acid or a base just by its pKa?

It is because the text-books will tell us, if it is a base, we should add more basic buffer to get it neutralized, then it will be absorbed by the organic solvent in the liquid-liquid extraction; however, you do other things if it is an acid. So I would like to seek your advice as to how to tell from a drug's structure or its pKa to see if it would act as an acid or as a base.

Thank you for your help!

In the first place, a N per se doesn't directly prove that it's a base. For example, imidazole contains both an acidic and a basic N.

As far as how to go about determining whether a compound is an acid or a base, the first line of attack is to check for ionization properties from a tabulated list of acids and bases. You won't necessarily find the compound you're interested in but certainly you should be able to find some close analog if you've got an extensive tabulation. My favorite place to look for pKa values is: Lange's Handbook of Chemistry but the recent additions of the Handbook of Chemistry and Physics by CRC Press also have a fairly extensive listing. The Merck Index also has pKa values for some drugs. If all else fails, one can certainly sort out whether something is an acid or a base by determining the effect of pH on retention in a reversed phase system (adjusting the pH so as to increase ionization should reduce retention). Of course, if there are multiple ionizable groups present interpretation of the pH influence could be more complex. Another option is to study the compound vs. pH using NMR.

You can also look at the retention pattern in reversed phase as a function of pH. If the molecule is neutral it will have more retention than when it is charged. Similarly, multiple charges give usually less retention than single charges. For example, benzoic acid is not charged at pH 2 and shows a lot of retention. At pH 7 it is completely ionized and exhibits much less retention. The opposite is true for a base, such as benzylamine. AT pH 10, it is not charged, at pH 7 it is charged. Therefore it has much less retention at pH 7 than at pH 10.
For your compound with the pK of 7, just change the pH to 6.5 and to 7.5 and you will know if it is an acid or a base.

I worked on a base whose pKa is 1.76; I also worked on a acid whose pKa was 9.8 9phenols). Botton line: pKa does not always indicate a base or acid.

When do we talk about an acid or a base??
Do someone have a definition of this material?

JL Shen

Nobody was suggesting that pKa alone would tell you whether a compound is an acid or a base. The point is that a bit of chemistry knowlege (eg. knowing that a carboxylic acid, a phenol, an alcohol and a sulfonamide are all acids) combined with a good tabulation of pKa's will allow one to accurately estimate the pKa of a compound in the table and thus predict the optimum pH for a separation. Some pKa tables will give you this information but you still need to know a bit of chemstry to figure out which pKa belongs to which ionizable group when multiple pKa values are involved

Thanx for all your help!

dear sir/mam,
i am new to chromatography,can i have an e-mail address where i can contact a chromatographer and get my basic questions cleared regarding GC,HPLC,LC-MS/MS

Here is one!