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The following message was posted to: PharmPK
Hello,
I am using Human, Rat and Mice plasma for determining the extraction
efficiency of the standard drugs. I am finding the differences in the
values obtained between different plasma.
It will be useful if i have the information about what is
contributing for this difference.
So if any one has the information or the reference about the contents
of the plasma proteins in different species, if it can be shared then
it will be of great help.
looking forward for the positive reply,
Bye,
B.L.Suresh
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The following message was posted to: PharmPK
It all depends on the type of extraction you are using. I suggest that you
examine the following aspects.
1. Type of solvent -- Acid base extraction or organic extraction.
2. Plasma - Extracting ratio
3. If you are using acid-base partition extraction you should examine the pH
effect.
4. Before jumping into the conclusion of species dependent organic
extraction efficiency, perform relevant statistical tests to document
significant species differences.
Personally I doubt if there exists such a species difference in extraction
recoveries as once you add sufficient organic solvent protein denaturation
occurs liberating all the drug available for partition into the organic
solvent.
Hope this helps.
Prasad NV Tata, Ph.D.
Mallinckrodt, Inc.
P.O. Box: 5840
675 McDonnell Blvd.
St. Louis, MO 63043
e-mail: prasad.tata.-at-.mkg.com
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hi
regarding the differences in the extraction recovery of the drug from the
various plasma it appears that these factors could be playing a
significant role.
a) the ratio of aqueous to organic volumes taken. greater ratios
sometimes gives better extraction of the drug from the matrix.
b) the extraction solvent being used
c) the degree to which you add a base or acid to bring the drug in the
unionized state.
even more there seems a less likelyhood that the proteins retain their
normal structure when you add a solvent to extract the drug. so i dont
feel that the nature of binding is affecting the release of drug from the
binding site. unless there is a covalent binding between the drug and the
plasma protein things get a bit complex. that is pretty rare.
Did you try protein precipitation technique for all three different
plasmas. Addition of acetonitrile/methanol to denature the plasma
proteins is another way to get good recovery. my experiences say that
this method gives pretty consistent results in terms of extraction
recovery from plasma of various species. with this technique if you find
no significant differences in your extraction recoveries between the
three biomatrices then i dont think it would be species difference but
could be the factors i mentioned above.
hope this helps u.
best of luck
manish issar
post doc associate
department of pharmaceutics
university of florida
box 100494
gainesville-32610
FL, USA
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The following message was posted to: PharmPK
Hello,
I remember something about differences in plasma binding in a paper
we did we Tom Tozer.
You could check
Reigner B.G., Bois F., Tozer T.N., 1993,
Pentachlorophenol carcinogenicity: Extrapolation of
risks from mice to humans,
Human and Experimental Toxicology, 12:215-225.
F. Bois
Frederic Y. Bois,
Unite de Toxicologie Experimentale, responsable
INERIS
Parc ALATA, PB2
60550 Verneuil en Halatte
FRANCE
tel: + 33 (0)3 44 55 65 96
fax: + 33 (0)3 44 55 66 05
email: frederic.bois.-at-.ineris.fr
web: http://sparky.berkeley.edu/users/fbois, http://www.ineris.fr
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