Fast and comprehensive multi-residue analysis

JournalofChromatographyA,1248(2012)104–121ContentslistsavailableatSciVerseScienceDirectJournalofChromatographyAjournalhomepage:∗,SaraRodríguez-Mozaza,DamiàBarcelóa,baCatalanInstituteforWaterResearch(ICRA),C/EmiliGrahit101,17003Girona,SpainbDepartmentofEnvironmentalChemistry,IDAEA-CSIC,C/JordiGirona18-26,08034Barcelona,SpainarticleinfoArticlehistory:Received9January2012Receivedinrevisedform18May2012Accepted22May2012Availableonline29May2012Keywords:PharmaceuticalsUltra-high-performanceliquidchromatographyQuadrupole-lineariontrapInformationdependentacquisitionMulti-residueanalyticalmethodabstractThepresentworkdescribesthedevelopmentofananalyticalmethod,basedonautomatedoff-linesolidphaseextraction(SPE)followedbyultra-high-performanceliquidchromatographycoupledtoquadrupolelineariontraptandemmassspectrometry(UPLC-QqLIT)forthedeterminationof81pharma-ceuticalresidues,coveringvarioustherapeuticgroups,andsomeoftheirmainmetabolites,insurfaceandtreatedwaters(influentandeffluentwastewaters,river,reservoir,seaanddrinkingwater).Forunequiv-ocalidentificationandconfirmation,twoselectedreactionmonitoring(SRM)transitionspercompoundaremonitored.Quantificationisperformedbytheinternalstandardapproach,indispensabletocorrectmatrixeffects.Moreover,toobtainanextratoolforconfirmationofpositivefindings,aninformationdependentacquisition(IDA)experimentwasperformed,withSRMassurveyscanandanenhancedproduction(EPI)scanasdependentscan.Compoundidentificationwascarriedoutbylibrarysearch,matchingtheEPIspectraachievedatonefixedcollisionenergywiththosepresentinalibrary.Themainadvantagesofthemethodareautomationandspeed-upofsamplepreparationbythereductionofextractionvolumesforsomematrices,thefastseparationofabignumberofpharmaceuticals,itshighsensitivity(limitsofdetectioninthelowng/Lrange),selectivity,duetotheuseoftandemmassspec-trometry,reliabilitysinceasignificantnumberofisotopicallylabeledcompoundsareusedasinternalstandardsforquantificationandfinally,theanalysisoftap,reservoirandseawaters,sinceinformationaboutoccurrenceofpharmaceuticalsinthesematricesisstillsparse.Aspartofthevalidationprocedure,themethoddevelopedwasappliedtotheanalysisofpharmaceuticalresiduesinwasteandsurfacewatersfromdifferentsitesinCatalonia(NorthEastofSpain).©2012ElsevierB.V.Allrightsreserved.1.IntroductionAmongthevastarrayofcontaminantsofanthropogenicori-ginreachingwatersupplies,pharmaceuticallyactivecompounds(PhACs)haveoneofthelargestinputsintotheenvironment.Severalstudieshaveproventhatsomepharmaceuticalsarenotcompletelydegradedduringconventionalwastewatertreatment[1–5]beingtherefore,dischargedintoreceivingwaterbodies(rivers,lakesandseas),whichmaybeusedassourcesfortheabstractionofdrink-ingwater.Itisdifficulttopredictwhichenvironmentalandpublichealthimplicationsmayarisefromtheoccurrenceofpharma-ceuticalsinfreshwaterecosystems.Someofthemostnotoriousadverseeffectsthattheymighthaveintheenvironment,besides∗Correspondingauthor.Tel.:[phone];fax:[phone].E-mailaddress:[e-mail](M.Gros).acuteorchronictoxicity,areresistantdevelopmentofpathogenicbacteriaduetotheoccurrenceofantibiotics[6,7],genotoxicity[8,9],andendocrinedisruption[10,11].Furthermore,somePhACssuchasantidepressantsandantibioticscanbepronetobioconcen-tration/bioaccumulationinaquaticorganisms,particularlyinfish[12–14].Therefore,thepresenceofpharmaceuticalsinenviron-mentalwaters,especiallyindrinkingwaterandrawwatersusedforitsproductionmustbeconsideredanimportantissueintermsofhumanhealthsafety.Inthiscontext,itisimportanttosetupfast,sensitiveandreliableanalyticalmethodsthatenablethedeterminationofawiderangeofpharmaceuticalsinenvironmentalwatersatthelowconcentra-tionlevelsfound.Nowadays,alargenumberofanalyticalmethodsarealreadyavailablefortheirdeterminationinbothsurfaceandwastewaters[15–21].Nevertheless,amorelimitednumberofmethodsfortheiranalysisindrinkingandseawatersarefoundintheliterature.Thisisprobablyduetotheanalyticaldifficulties0021-9673/$–seefrontmatter©2012ElsevierB.V.Allrightsreserved.(2012)104–121105encounteredtoquantifythemattheultra-tracelevelsthattheymightactuallybepresent.Currentresearchregardingthedevelopmentofanalyticalmeth-odsforthedeterminationofpharmaceuticalsinenvironmentalmatricesisorientedtowardimprovementsofthesemethodologies,withtheaimofincreasingsamplethroughput,minimizingsam-plemanipulation,decreasingsolventconsumptionandincreasingoverallmethodefficiency,intermsofselectivityandsensitivity.AdvancesonhyphenatedLC–tandemMS,thetechniqueperexcel-lenceforpharmaceuticaldetermination,havedriventoimprovedsensitivity,allowingthedetectionofsub-pptconcentrations,aswellastotheidentificationofabignumberofcompoundssimul-taneouslywithoutlosingsensitivity.Ontheotherhand