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Dear Sirs,
I am studying dihydropyrimidine dehydrogenase (DPD) activity by means
of the measure of uracil/dihydrouracil in plasma samples of patients
treated with capecitabine. We tried to develop a chromatographic
method based on Ciccolini et al (A simple and rapid HPLC method for
5FU assay in plasma and possible detection of patients with impaired
dihydropyrimidine dehydrogenase (DPD) activity (Joseph Ciccolini, C
Mercier,M F Blachon, R Favre J Clin Pharm Ther. 2004 Aug;29(4):
307-15.) The mobile-phase consisted of a KH(2)PO(4) salt solution
(0.05 M) + 0.1% triethylamine (TEA) pumped at 0.4 mL/min (25 cm RP-18
column). U and UH2 elution was monitored at 210 nm
Anyway we have some specifity problems since we could not separate an
interference at the same retention time of UH2 in plasma. I do not
know if HPLC methods are used , in a routine clinical setting, to
estimate DPD activity (or if some group have any experience with
another chromatographic system)
I would appreciate some help on this topic.
regards,
Dr Guillermo Bramuglia
Profesor Adjunto
Catedra de Farmacologia
Facultad de Farmacia y Bioquimica
UBA
Buenos Aires. Argentina
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Dear Guillermo,
You can find an intersting paper dealing with uracil and dihydrouracil
determination to predict 5-FU toxicity:
Gamelin E, Boisdron-Celle M, Guerin-Meyer V, Delva R, Lortholary A,
Genevieve F, Larra F, Ifrah N, Robert J.Correlation between uracil and
dihydrouracil plasma ratio, fluorouracil (5-FU) pharmacokinetic
parameters, and tolerance in patients with advanced colorectal cancer:
A potential interest for predicting 5-FU toxicity and determining
optimal 5-FU dosage.J Clin Oncol. 1999 Apr;17(4):1105.
You can also find, by the same authors, a paper dealing with an HPLC
method used in routine to determine plasma concentrations of
halogenopyrimidines (mainly used for the 5-FU plasma concentration
determination):
Gamelin E, Boisdron-Celle M, Turcant A, Larra F, Allain P, Robert
J.Rapid and sensitive high-performance liquid chromatographic analysis
of halogenopyrimidines in plasma.J Chromatogr B Biomed Sci Appl. 1997
Aug 1;695(2):409-16.
This group (Gamelin and Boisdron-Celle) is working on DPD thus there
are other papers you can find in Pubmed that might help you.
Hope this helps
Elisabeth Rouits
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