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Dear all,
We have developed a HPLC method for the analysis of 5-FU in human plasma
but we still have to overcome extraction problems (poor yield, lack of
selectivity, dreadful blank plasma threshold...).
Does anybody know a suitable solid/liquid extraction method? Since we need
this method for clinical pharmacokinetics purpose, a L.O.Q around 2 ng/ml
is required.
Most of the methods described in the literature are time consuming and
don't suit to therapeutic monitoring.
Any suggestion is welcome,
Pr. Jacques Catalin
Laboratoire de Toxicocin=E9tique et Pharmacocin=E9tique
Facult=E9 de Pharmacie
Marseille, France.
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[A few replies - db]
From: "Laurent Rivory"
Organization: Central Sydney Area Health Service
To: PharmPK.at.pharm.cpb.uokhsc.edu
Date: Wed, 16 Sep 1998 09:11:12 +1000
Subject: Re: PharmPK 5 fluoro-uracil extraction in plasma
Reply-To: lrivory.at.canc.rpa.cs.nsw.gov.au
Priority: normal
Dear Professor Catalin,
Have you considered the method published by E Gamelin et al J.
Chromatogr B 695:409-416 (1997). We haven't any experience with this
but it appears to be a well validated and optimised method.
Regards
Laurent Rivory
Senior Scientist
Sydney Cancer Centre
---
From: servicio farmacia
To: Multiple recipients of PharmPK - Sent by
,
"'PharmPK.-a-.pharm.cpb.uokhsc.edu'"
Subject: RE: PharmPK 5 fluoro-uracil extraction in plasma
Date: Wed, 16 Sep 1998 10:13:32 +0200
Encoding: 49 TEXT
Mime-Version: 1.0
Dear jacques:
We have recently developed a pk/pd study with 5-FU in cancer womans. We
used our own HPLC method, and although it was not precisely ideal, it did
work reasonably well for our purposes. We estimated a LOQ of 0.012 mcg/ml,
calculated by multiplying x3 the standard deviation of the lowest control
(0.05 mcg/ml). If your problem is sensitivity, you can change some
parameters (column...) to increase it. Our patients had 5-FU concentrations
after 1 hour of the administration (450 mg/sqm) of 0.05 - 0.1 mcg/ml.
If you are interested in specific details of our method, do not hesitate to
contact with us;
JP Ordovas Baines
Pharmacy Service
Hospital Universitario Dr. Peset
Valencia (Espana)
email: farmpese.-at-.san.gva.es
---
X-Sender: catalin.-a-.rousseau.timone.univ-mrs.fr (Unverified)
Date: Wed, 16 Sep 1998 11:10:57 +0200
To: PharmPK.at.pharm.cpb.uokhsc.edu
From: Catalin Jacques
Subject: extraction of 5-FU in plasma
Mime-Version: 1.0
Dear Dr. Mertes and Baines,
Thanks for your comments; we need this method for monitoring 5 days
400mg/day 5-FU infusions in patients. The Css is around 40ng/ml.
The current solid/liquid extraction method we've got gives good yield(thus
acceptable sensitivity) but rather poor selectivity, especially with
endogenous compounds.
Attempts to optimize the extraction selectivity affect dramatically the
recovery and involve counter-extractions or other time-consuming steps,
which doesn't meet the requirements of routine multi-samples analysis.
Optimization of mere chromatograhic parameters such as type of column
didn't improve much (better separation was obtained allong with beautiful
tailing effect), and since 5-Fu has a poor U.V absorbance, the detection
parameters can't be improved either.
I don't see the point in using a tritiated internal standard!
All the best,
Pr. Jacques Catalin
Laboratoire de Toxicocin=E9tique et Pharmacocin=E9tique
Facult=E9 de Pharmacie
27, Bd Jean Moulin
13385 Marseille cedex 05
France
Tel: (33) (0)4 91 83 55 09
Fax: (33) (0)4 91 83 56 67
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Dear Pr Catalin,
Our interest for 5 FU monitoring have recently led us to meet Ms Michele
BOISDRON, who collaborate with E. GAMELIN (see the reference in J. Chrom
B.indicated to you by L. Rivory), both of them being very up-to-date in
anticancer drug monitoring and particularly 5 FU monitoring.
I advise you to contact Michele at the CAC Paul Papin of Angers;
02/41/35/27/00. I am sure that her experience will be helpful to you.
Kind regards and "bonjour =E0 tous!".
Chantal Le Guellec
Laboratoire de pharmacologie
CHU Bretonneau TOURS, France.
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Just read your e-mail. I was involved in group evaluating 5FU by itself
and in the presence of ftorafur. Our research biochemist evolved a HPLC
assay which achieved the necessary sensitivities and which was highly
specific in the presence of ftorafur. An important part of the was the
sample preparation and clean up prior to use of the HPLC. The assay was
published in Journal of Pharmaceutical Sciences, 1981; 70:1163-1166.
The lead author's name was Cecil Hornbeck. Title = Serum Concentrations
of 5-Fluorouracil with an Improved Liquid Chromatographic Assay for
5-Fluorouracil in the Presence of Ftorafur.
Hope this is helpful.
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Just read your e-mail. I was involved in group evaluating 5FU by itself
and in the presence of ftorafur. Our research biochemist evolved a HPLC
assay which achieved the necessary sensitivities and which was highly
specific in the presence of ftorafur. An important part of the was the
sample preparation and clean up prior to use of the HPLC. The assay was
published in Journal of Pharmaceutical Sciences, 1981; 70:1163-1166.
The lead author's name was Cecil Hornbeck. Title = Serum Concentrations
of 5-Fluorouracil with an Improved Liquid Chromatographic Assay for
5-Fluorouracil in the Presence of Ftorafur.
Hope this is helpful.
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