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=46rom: fabrice lagrange
Date: Thu, 20 Sep 2001 10:11:36 +0200
Subject: Re: PharmPK Ketoprofen SR
The first question is: do you really need a stereoselective method ?
see the algorythm of Karim A. Enantioselective assays in comparative
studies of racemic drugs formulation: nice to know or need to know? J
Clin Pharmacol 1996;36:490-499.
There are several ketoprofen HPLC methods available with derivatization or
without chiral columns. Since our operating procedure is in french, Read:
Davies NM Methods of analysis of chiral NSAIDs. Clin
P=E9hourcq F, Lagrange F, Labat L, Bannwarth B. Simultaneous
measurement of flurbiprofen, ibuprofen, and ketoprofen enantiomer
concentrations in plasma using L-leucinamide as the chiral coupling
component. J Liq Chromatogr ; 1995; 18 :
Lagrange F, Fabre T, P=E9hourcq F, Durandeau A, Bannwarth B. In
vitro distribution of ketoprofen enantiomers in articular tissues of
osteoarthritic patients. J Pharm Biomed Anal 2001 26:719-725.
There is a more recent method from Pehourcq F Jarry, and Bannwarth B,
without derivatization. But I don't know if it is published yet.
You have to take to account that method may use derivatization instead
of column with chiral stationnary phases. The major problem, however, is tha=
you should avoid stereoconversion during the extration or
It is important to Read:
Ducharme J, Fernandez C, Gimenez F et al. Critical issues in chiral
drug analysis in biological fluids by HPLC. J Chromatograph B Biomed
Wright MR, Jamali F. Limited extent of stereochemichal conversion of ch=
NSAIDs induced by derivatization methods employing ethyl chloroformate.
J. Chomatograph. 1993;616:59-65
There is also a problem with the stability of the acylglucuronides metabolit=
see: Hayball PJ Formation and reactivity of acyl glucuronides: the
influence of chirality
=46rom: "Tom Dowling"
Date: Thu, 20 Sep 2001 12:54:45 -0400
Subject: Re: PharmPK Ketoprophen
The following message was posted to: PharmPK
=46or our ketoprofen PK study (single oral dose, 200mg), we analyzed
plasma samples using the following HPLC/UV procedure:
MP: 40% ACN, 2% THF, in 50mM sodium acetate buffer.
Extraction: double liquid-liquid, using M-t-butyl ether:hexane (4 mL
x 2), evap under N2, recon in MP, inject onto C18 column. UV
detection at 254 nM.
Conc. range: 100 - 3000 ng/mL.
Hope this helps,
Thomas C. Dowling, PharmD, PhD
Department of Pharmacy Practice and Science
Pharmacokinetics and Biopharmaceutics Laboratory
University of Maryland School of Pharmacy
100 N. Penn St., Rm. 540D
Baltimore, MD 21201
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