A review of analytical methods for the determination

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1、AnalBioanalChem(2010)397:1191–1201DOI10.1007/s00216-010-3633-8REVIEWAreviewofanalyticalmethodsforthedeterminationof5-fluorouracilinbiologicalmatricesMassimoBreda&SimonaBarattèReceived:25May2009/Revised:24February2010/Accepted:3March2010/Publishedonline:1

2、1April2010#Springer-Verlag2010Abstract5-Fluorouracil(5-FU)isacytostaticagentthatthepast20years5-FUhasbeenusefulasacytostaticagenthasbeenwidelyusedinthetreatmentofvarioussolidinthetreatmentofsolidtumours,includingbreastcancer,tumoursformorethan20years,and

3、isstillconsideredtobegastrointestinaladenocarcinomaandsquamouscellcarcinomasamongthemostactiveantineoplasticagentsinadvancedoftheheadandneck[1–4].Recently5-FUinassociationwithcolorectalcancerandmalignanciesoftheheadandneck.Airinotecanandradiotherapyhasbe

4、enusedforthetreatmentoflargenumberofnon-chromatographicandchromatographicrectalcancer[5].methodsforthequantitationof5-FU,relatedprodrugsandtheirmetabolitesinbiologicalmatriceshavebeendevelopedMetabolisminthelast30yearstosupportpreclinicalandclinicalstudi

5、es.However,5-FUmonitoringhasnotbeenwidelyused,atleastToxicityremainsanimportantparametertobeconsiderednotintheUSA,andcertainlynotoutsidetheclinicalresearchwhen5-FUisadministered,as5-FUoftencausesseveresetting,giventheabsenceofsimple,fastandinexpensivegas

6、trointestinaltoxicityandmyelosuppression[6].Forthistestingmethodsfor5-FUmonitoring.Recentdevelopmentsreasontoxicityhasbeeninvestigatedinassociationnotonlywithtestingbasedonliquidchromatography–tandemmasswiththepharmacokineticsoftheparentcompoundbutalsosp

7、ectrometryandananoparticleantibody-basedimmunoassaywiththedrug’smetabolism.Themechanismofactionof5-FUmayfacilitateroutinemonitoringof5-FUindailyclinicalisbasedonanabolicconversionintocytotoxicnucleotides,practice.Inthisreviewtheadvantagesanddisadvantages

8、oftheusingseveralpyrimidinemetabolicpathwayenzymes.Asbioanalyticalmethodsdevelopedandusedfor5-FU,itsillustratedinFig.2,thesenucleotidescanbeformedbymetabolitesandrelatedprodrugsarediscussed.conversionandsequentialconversio