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[Still chemistry but.;-)..db]
Dear David
I am developing an HPLC method to look at the pharmacokinetics of
verapamil enantiomers.I need this agent for derivatizing verapamil to
separate to enantiomers.
with many thanks
Dr mostafavi
> This looks more like synthetic chemistry than PK/PD.
>
> David
>
> >The following message was posted to: PharmPK
> >
> >Hello all
> >
> >I'm trying to use (-)menthyl chloroformate (a chiral derivitizing
> >agent) for a project. I do not know what is its solvent. I've tried
> >a few solvents (such as chloform, acetonitril ethanol, ) but no
> >one is really work. If anyone know what is its solvent please let me
> >know.
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Dear Abolfazl,
(-)menthyl chloroformate is soluble in Acetonitrile. Please note that at
room temp chemical reaction will only take place between Norverapamil and
MCF. You may need to heat or use microwave oven for reaction between
Verapamil and MCF.
I will recommend using a chiral column.
Thanks,
Masood Bhatti
Group Leader
Pharmacokinetic Drug Metabolism
Purdue Pharma
New York
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Are you sure you need to derivatize?:
1: Brandsteterova E, Wainer IW.
Achiral and chiral high-performance liquid chromatography of verapamil and
its
metabolites in serum samples.
J Chromatogr B Biomed Sci Appl. 1999 Sep 24;732(2):395-404.
PMID: 10517362 [PubMed - indexed for MEDLINE]
2: Fried K, Wainer IW.
Column-switching techniques in the biomedical analysis of stereoisomeric
drugs:
why, how and when.
J Chromatogr B Biomed Sci Appl. 1997 Feb 7;689(1):91-104. Review.
PMID: 9061485 [PubMed - indexed for MEDLINE]
3: Schwartz JB, Capili H, Wainer IW.
Verapamil stereoisomers during racemic verapamil administration: effects of
aging and comparisons to administration of individual stereoisomers.
Clin Pharmacol Ther. 1994 Oct;56(4):368-76.
PMID: 7955798 [PubMed - indexed for MEDLINE]
4: Abernethy DR, Wainer IW, Longstreth JA, Andrawis NS.
Stereoselective verapamil disposition and dynamics in aging during racemic
verapamil administration.
J Pharmacol Exp Ther. 1993 Aug;266(2):904-11.
PMID: 8355215 [PubMed - indexed for MEDLINE]
5: Shibukawa A, Wainer IW.
Simultaneous direct determination of the enantiomers of verapamil and
norverapamil in plasma using a derivatized amylose high-performance liquid
chromatographic chiral stationary phase.
J Chromatogr. 1992 Feb 7;574(1):85-92.
PMID: 1629292 [PubMed - indexed for MEDLINE]
6: Chu YQ, Wainer IW.
Determination of the enantiomers of verapamil and norverapamil in serum
using
coupled achiral-chiral high-performance liquid chromatography.
J Chromatogr. 1989 Dec 29;497:191-200.
PMID: 2625456 [PubMed - indexed for MEDLINE]
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Greetings Abolfazl and Masood,
I would concur with Masood. A Chiralpac AD from Daicel Chemical Industries
provides excellent resolution of R,S Verapamil and R,S norverapamil and
obviates the need for pre-column chemistry.
Shubikawa and Wainer published an HPLC method using this column and
fluorescence detection in 1992.
See J. Chorm Bio App 1992;574:85 -92.
If the cost of the columns seems high, the cost of your derivitizing agent
does eventually add up if you are
doing this assay for a while. The chiral columns are really quite robust if
you take good care of them.
Hope this is of some help. Best regards to you both.
Patrick R. Mayo, B.Sc. (Pharm), Ph.D.
PharmPK Discussion List Archive Index page
Copyright 1995-2010 David W. A. Bourne (david@boomer.org)