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Dear Group
I need your advise related to calculation of %ionized for compounds having multiple pKa values (more than 1). The basic Henderson-Hasselbalch equation describes the calculation of %ionized for compounds with only one pKa (weakly acidic or basic) at particular pH. If the compound has multiple pKa values, is there any extended Henderson-Hasselbalch for calculation of %ionized?
If not, is there any other method for calculation of %ionized?
Thank You
Best Regards Sivacharan Kollipara Scientist Pharmaceutical and Analytical Development Novartis Healthcare Pvt Ltd Hyderabad, India.
[Maybe the applets on http://www.boomer.org/c/d1/
will help - db]
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The following message was posted to: PharmPK
Dear Sivacharan,
the toolsof software MarvinSketch
[ChemAxon] give you all the % of different ionized forms changing the pH.
I hope this can help you.
Best regards
Elena Strocchi
--
Elena Strocchi - Pharmacokinetics and Metabolism Lab
Organic Chemistry Dept. - University of Bologna
Viale Risorgiemnto 4- 40136 Bologna- Italy
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The following message was posted to: PharmPK
Dear Sivacharan
There are plenty of these available in the literature but not all
correct.
Leo Berezhkovskiy provides a nice summary together with the reasoning
behind the equations (which corresponds to the approach that has been
taken within Simcyp simulations for many years):
Berezhkovskiy (2010) The Corrected Traditional Equations for Calculation
of Hepatic Clearance that Account for the Difference in Drug Ionization
in Extracellular and Intracellular Tissue Water and the Corresponding
Corrected PBPK Equation. JPharmSci
Regards
David Turner PhD
Principal Scientist
Simcyp Limited
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The following message was posted to: PharmPK
Sivacharan, physical pharmacy by Alfred Martin is a good reference for this. It has some solved examples as well for this. In general, if multiple pKas are present, the molecule can get mono or di or multiple protonated a or deprotonated.
Regards, Ayyappa Chaturvedula
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Hi Sivacharan,
Of course for multiple pKa drug, generalized Handerson-Hasselbalch (HH) equation does not suffice. For, such coumpound an expression derived by pooling individual HH equation will avail the percent ionized total as well as % ionized with respect to each group. You can plot Pjerrum plot of the % ionized versus pH for each group of which the intersection gives the net ionized and individual ionized species at particular pH. You can find standard equations in literature for this as well.
Hope this will help.
Amrit
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The following message was posted to: PharmPK
Hi,
You can try by using GLPKa instrument (mfg by Sirius).
Regards,
S.Basu
Principal Scientist (DMPK & TOX)
Sai Advantium Pharma Ltd.,
Hinjewadi, Pune - 57.
E-Mail : sudipta.b.-a-.saiadvantium.com
[Updated to the Sirius T3 http://www.sirius-analytical.com/products/SiriusT3.shtml
- db]
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