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Direct, automated and sensitive determination of glyphosate and related anionic pesticides in environmental water samples using solid-phase extraction on-line combined with liquid

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Tiêu đề Direct, Automated and Sensitive Determination of Glyphosate and Related Anionic Pesticides in Environmental Water Samples Using Solid-Phase Extraction On-line Combined with Liquid Chromatography Tandem Mass Spectrometry
Tác giả J. Lúpez-Vỏzquez, L. Pộrez-Mayỏn, V. Fernỏndez-Fernỏndez, R. Cela, I. Rodrớguez
Trường học University of Santiago de Compostela
Chuyên ngành Analytical Chemistry
Thể loại research article
Năm xuất bản 2022
Thành phố Santiago de Compostela
Định dạng
Số trang 9
Dung lượng 1,96 MB

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Nội dung

An automated procedure for the simultaneous determination of six anionic pesticides, including glyphosate (GLY) and its transformation product aminomethylphosphonic acid (AMPA), was developed and applied to the analysis of environmental water samples.

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journalhomepage:www.elsevier.com/locate/chroma

J López-Vázquez, L Pérez-Mayán, V Fernández-Fernández, R Cela, I Rodríguez∗

Department of Analytical Chemistry, Nutrition and Food Sciences Research Institute on Chemical and Biological Analysis (IAQBUS) Universidade de

Santiago de Compostela, 15782-Santiago de Compostela, Spain

a r t i c l e i n f o

Article history:

Received 10 October 2022

Revised 29 November 2022

Accepted 30 November 2022

Available online 5 December 2022

Keywords:

Glyphosate

Zwitterionic pesticides

On-line solid-phase extraction

Liquid chromatography mass spectrometry

a b s t r a c t

An automated procedure for the simultaneous determination of six anionic pesticides, including glyphosate(GLY) and itstransformationproductaminomethylphosphonic acid(AMPA), was developed and applied tothe analysis ofenvironmental water samples.The proposed methodcombineson-line concentration of water samples (0.160 mL), with compounds separation in an anion-exchange liquid chromatography(LC)column,followed bytheirselectivedetermination bytandemmass spectrometry (MS/MS).Theglobalprocedurewascompleted in25 min,providinglimits ofquantification(LOQs) be-tween5ngL−1and20ngL−1,withreducedeffectofthesurfacewatermatrixintheefficiencyof pro-cess(SPEandionizationyields).Themethodwasappliedtotheanalysisofgrabsamplesobtainedfrom threewatersheds,intworuralandoneresidentialarea,inGalicia(NorthwestSpain).Outofsix investi-gatedcompounds,Fosetyl,AMPAandGLYwerenoticedinthesetofprocessedsamples.Theirdetection frequenciesincreasedfrom12%(Fosetyl)to88%(AMPA).Medianconcentrationsfollowedthesametrend varyingfrom 9ng L−1 (Fosetyl)to 44ngL−1 (AMPA).The higherlevels and thelarge seasonal varia-tionsintheresiduesofthelatterspecieswerenoticedinsmallriversaffectedbydischargesofmunicipal sewagetreatmentplants(STPs)

© 2022 The Author(s) Published by Elsevier B.V ThisisanopenaccessarticleundertheCCBY-NC-NDlicense (http://creativecommons.org/licenses/by-nc-nd/4.0/)

1 Introduction

Glyphosate(GLY)isanon-selectiveherbicideimpairingthe

syn-thesis ofaromaticaminoacidsby plants.Itiswidely employedto

control the development of weeds in permanent and transgenic

cropsandtohomogenizetheharvestofGLYsensitiveplants

Addi-tionallyto agricultureuses,GLYisalsoappliedto destroy

vegeta-tiongrowinginthelimitsofroads,aswellasinforestry,tocontrol

thedevelopmentofwaterandnutrientscompetingplants[1]

After application, GLYisassumedtoremainbondedtocations

existing in soil, particularly to iron, copper and aluminum

con-taining minerals Thisbehavior, combined withan estimatedsoil

half-life of a few days [2], turns in a low groundwater ubiquity

score(GUSindex0.21)[3],pointingouttoareducedriskof

leach-ingtogroundwaterand/orsurfacewater.Aminomethylphosphonic

∗ Corresponding author

E-mail address: isaac.rodriguez@usc.es (I Rodríguez)

acid (AMPA) is the main transformation product of GLY in soils AMPAisalsoaZwitterionicspecies,withaslightlyhigherhalf-life

insoilthantheparentherbicide.Despitedirectmigrationofboth compoundstotheaquaticmediaisunlikely,themisuseofthe par-ent herbicide, runoff transport associated to soil particles during heavy rain events,wind erosion andatmospheric drift might re-sultinthecontaminationofsurfacewaterswithGLYand/orAMPA [4].Furthermore,phosphatefertilizersincrease thereleaseofGLY, andAMPA, fromsoil to thewater phase,due todisplacement of bothcompoundsfromtheirmetallicquelates[5].Inlinewiththese comments,severalstudies havereportedthepresenceofGLYand AMPAin surfacewaterfromagriculture impactedbasins[6]and, particularly,instreamsdrainingtransgeniccrops[7–9].Anational scale survey carried out in USA (more than 3000 samples were takenfrom70riversandstreamsfortwoyears) hasreported de-tection frequencies and medianconcentrationsof 74% and 50ng

L−1 for GLY, with even higher figures for AMPA [9] Residues of thesepesticides are not limitedto intensive agriculture areas In fact,inGermany,theoccurrenceandtheaverageconcentrationsof

https://doi.org/10.1016/j.chroma.2022.463697

0021-9673/© 2022 The Author(s) Published by Elsevier B.V This is an open access article under the CC BY-NC-ND license

( http://creativecommons.org/licenses/by-nc-nd/4.0/ )

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it requires removing the excess of derivatization reagent and/or

the reaction by-products before LC analysis Thus, other

analyti-cal methods have been proposed Although some of them have

explored alternative derivatization reactions, in some cases

com-bined withgaschromatography-basedtechniques[13,14],the

ma-jor stream considers directanalysis ofnativecompounds,

explor-ingdifferentLCstationaryphases.Among them,hydrophilic

inter-action, mixed-modeandanionicexchange columnshavebeen

al-readytestedfortheseparationofboth species,andother anionic

and/or Zwitterion pesticides, either in food or in water samples

[15–22] Other compounds withsimilar features (anionic

charac-ter andhighpolarity)toGLYincludethefungicideFosetyl-Al[23],

theherbicideglufosinate(GLU)andtheenvironmental

transforma-tion products of the latter compound N-acetyl glufosinate (NAG)

and 3-(methylphosphinic)propionic acid(MPPA)[24] Itis worth

notingthatneitherFosetyl,norMPPAcanbedeterminedusingthe

FMOC–Cl derivatization approach.Advances in the determination

of these anionic, metal complexing compounds are not only

re-latedwithevaluationofnewstationaryphases, butalsowiththe

testingofdifferentadditives(i.e.medronicacid)[25]and/orPEEK

linedcolumnspreventingnon-reversibleinteractionsbetween

ana-lytesandmetalcations,eithercomingfromsamples,columnwalls

and/ortheLCinstrumentitself[17]

AnotherlimitationfordirectanalysisofZwitterionicspeciesis

the difficulty to extract and concentrate these compounds from

water samples Direct injection of large sample volumes, use of

anion-exchange solid-phaseextraction(SPE)sorbents, orselective

concentration of pre-defined compounds (i.e GLY) with

molecu-larlyimprintedpolymers(MIP),aresomeofthesolutionsreported

in theliterature [18,21,26].Tothe bestofourknowledge, neither

these extractionprocedures havebeenon-line combinedwithLC

andtandemmass spectrometry(MS/MS)detection, northey have

reachedsimilar LOQstothosereportedforthe FMOC–Clprotocol

[11,12]

Thismanuscriptpursuitstwoaims.The firstwasassessingthe

performance of an automated, direct LC-MS/MS methodology for

the simultaneousdeterminationofGLY,AMPAandtwoadditional

anionic pesticides(Fosetyl-aluminum; GLU) andalsothe

environ-mentaltransformationproductsofthelater:NAGandMPPAin

en-vironmentalwatersamples.The secondaimwastoevaluatetheir

occurrence and possible seasonal variations, in samples obtained

fromthreedifferentwatershedsinGalicia(NorthwestSpain)

2 Material and methods

2.1 Standards, solvents and sorbents

ThestandardsofGLY,AMPA,Fosetyl-aluminum,GLUandMPPA

were acquiredfromSigma-Aldrich (St Louis,MO,USA).NAG was

provided by LGC standards (London, UK) Native parent

pesti-cidesandtheirtransformationproductswereanalyticalgrade

qual-ity, witha purity above 98% Theirchemical structures are given

as supplementary information, Fig S1 Isotopically labelled

ana-logues ofGLY (1,2–13C2,15N; 99%),AMPA (13C,15N,97%),

Fosetyl-aluminum-d15(95%) andGLU-d3 (98%) were providedby Toronto

Ammoniumbicarbonateandformicacid, bothLC-MSpurity,were suppliedbyHoneywellFluka(Seelz,Germany)andFisherscientific (Portsmouth,NH,USA),respectively

2.2 Samples

Samplesemployedduringmethoddevelopmentandvalidation includeultrapurewater,surfacewaterobtainedfromstreamsand rivers, mineral water (commercially available bottled water), tap water andwell water Regarding environmental studies, 17 sam-pling points were selected from three areas in Galicia (Norwest Spain),Fig 1A.Points S1 to S13 correspond toa hilly rural area, withalow populationdensitydistributedintinyvillages and dis-persedfarms,devotedtovineyardproduction.Inthisregion, sam-ples were obtainedfromthe twomain rivers draining vineyards: Avia(S2, S3, S4)andMiño(S5, S6, S9 andS11),aswell as some tributarystreamsandgroundwatersprings,Fig.1B.PointsS14and S15correspondtoasmallriver(Tinto),flowingthrougha residen-tial, peri–urban area, with a low impact of agriculture activities Samplingsiteswereplacedupstream(S14)anddownstream(S15) thedischargepointofaSTPservingapopulationof13,000 inhabi-tants,Fig.1C.Inbothareas,foursamplingcampaignswerecarried outfromthebeginningofspringtosummer

PointsS16andS17wereplacedinamediumsizeriver(Limia) flowingthrough arural flatarea ofarable fields,devoted to pro-duction of cereals (maize and wheat) andpotatoes, Fig 1D The riveralsoreceivesthedischargeoftreatedwaterfromaSTP serv-ingapopulationof12,000inhabitants.Inthisarea,bothsampling pointswere placedafterthe municipal STP.Three sampling cam-paignswerecarriedouttodetectpotentialagricultureusesof her-bicidesbeforetillageofagriculturefields(spring),andasdriersof wheatandpotato crops,inthemiddleofsummerandthe begin-ningofautumn,respectively

TableS1 summarizesthe exactpositionof eachpoint andthe samplingdates.Withtheexceptionofthesurfacewaterreservoir

inMiñoriver,significantvariationsintheflowoftherestofrivers andstreamswerenoticedduringthesamplingperiod.Particularly, lowflows wereobservedinthelattercampaigninthethree con-sidered areas Available data for major rivers, obtained from re-gionalwatermanagementauthorities,arecompiledinTableS2 Samplesweretakeninpolypropyleneflasksandtransportedto the laboratory atroom temperature, within 4 h Thereafter, they were eitheranalyzed inthe next 24h,or storedat−20 ºCuntil analysis.Tap waterwas collectedinthe laboratory whenneeded andmineralwaterwaspurchasedinlocalmarkets

2.3 Sample preparation

Sample preparation involved filtration (case of environmental water samples), using 0.22 μm hydrophilic polytetrafluoroethy-lene (PTFE) syringe filters acquired from Phenomenex (Torrance,

CA, USA),addition ofthe mixtureof surrogate standards(SSs)at

500 ng L−1, andanalysis by SPE on-line connectedwith the LC-MS/MSsystemunderconditionsreportedinthenextsection

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Fig 1 Map of sampling points (S1-S17) in the three different areas in Galicia (Northwest Spain)

2.4 LC-MS/MS equipment and determination conditions

The LC-MS/MS system was an Agilent 1290 Infinity II liquid

chromatograph connected to an Agilent 6495, triple quadrupole

(QqQ) massspectrometer, equipped withajet stream ESI

ioniza-tion source.Inadditionto thebinaryanalyticalpump, theLC-MS

platform included an auxiliary pumpto deliver calibration

stan-dards andsamples through theSPE cartridge, on-line coupledto

theanalyticalcolumn.Both,cartridgeandcolumn,wereconnected

using a10-port, 2-possitionvalve Fig S2showsa schemeofthe

valve during on-lineSPEconcentration anddesorption steps The

LCinstrumentincludedanautosampler,witha100μLneedleloop,

and an extended injector seat permitting to accommodate up to

0.5mLsamplesbeforebeingtransferredtotheSPEcartridge

Compoundswereseparatedusinga MetrosepASupp6,strong

anionic exchangecolumn(150mmx2mm,5μm),acquiredfrom

Metrohm(Herisau,Switzerland).Themobilephaseusedinthe

an-alyticalcolumnconsistedofamixtureofACN:ultrapurewater(1:1)

with a 45 mM concentration of bicarbonate ammonium (phase

A);andultrapurewater,50mMinbicarbonateammonium(phase

B) Its composition wasprogrammed as follows: 0–3 min, 0% B;

7.5min,35% B; 10min,60% B; 11–18 min,100%B; 18.1–25min,

0% B The flowrateof mobile phase andthecolumn temperature

were0.3mLmin−1 and30ºC,respectively.Intheauxiliarypump,

ultrapure water(phaseC)andMeOH(phaseD)wereused.AsSPE

sorbent, we employed an anionic exchange pre-column (5 mm x

4 mm, 5μm) from Metrohm, withthe same stationaryphase as

theanalyticalcolumn,andalargerinternaldiameter

Underfinalworkingconditions,0.160mLsampleswereloaded

in the pre-column using ultrapure water(phase C), ascarrier at

0.5 mL min−1 for 1 min, then the flowrate of ultrapure was

in-creasedto1mLmin−1,andmaintaineduntil2.5min.Inthisstep,

anionicspecieswereretainedintheon-lineconnectedpre-column,

whilst other componentsflowed towaste After 2.5min, the

10-port valve switched to elution position, with compounds being

transferred from the pre-column to the analytical column The

valve returned toits initial position(loading mode)after15 min,

and the SPE sorbent was conditioned using MeOH (15–18 min,

1 mL min−1) followed by ultrapure water (18.1–25 min, 0.5 mL min−1)

Nitrogenwasemployedasdrying(11Lmin−1,150ºC),sheath (12Lmin−1,400ºC)andnebulizinggas(55psi)intheESIsource Theneedlevoltages were3000Vand1500V forESI(+) andESI (-)modes,respectively.Thefragmentorvoltagewas166V.Table1 gathers the m/z values forprecursor and product ionsfor native pesticidesand SSs.Retention times andratios between qualifica-tion(Q2andQ3)andquantification(Q1) transitionsofeach com-poundarealsogiveninTable1

2.5 Extraction efficiency and samples quantification

TheefficiencyoftheSPEon-lineprocesswasassessed compar-ingthe slopeofcalibrationcurvesobtainedforspikedaliquotsof riverandmineralwater(50ngL−1 to2000ngL−1,n= 6 differ-entconcentrationlevels)withthosecorrespondingtostandardsin ultrapure water withsame concentration levels Responses (peak areas) obtainedforthe Q1 transitionofeach compound, without any correction with SSs, were plotted against added concentra-tions Slope ratiosabove the unit correspond to increased appar-entextractionefficienciesforrealsamplescomparedtostandards

inultrapurewater,whilevaluesbelowtheunit havetheopposite meaning.Changesintheslopesofcalibrationcurvescanberelated

to variationsinthe efficiencyof the SPEprocess itself, and/or to variableyieldsofESIionizationdependingonthesamplematrix The accuracy of the method was estimated as the difference betweenconcentrationsmeasuredforspikedandnon-spiked frac-tions of differentwater samplesdivided by the added value and multipliedby 100 Experimental concentrationswere determined againstcalibrationstandardspreparedinultrapurewater(5ngL−1

to 5000ng L−1), containingsame level ofSSs as watersamples Peakareasforeachcompoundwerecorrectedwiththatmeasured forthecorrespondingSS,Table1

Witheachsetofenvironmentalwatersamples(15 to20 sam-ples, plus calibration standards were analyzed in duplicate per

3

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d GLY- 13 C 2 , 15 N 8.22 + 173 91 (8) 62 (17)

a to d, denote the surrogate standard assigned to each pesticide

CE, collision energy (eV)

batch),oneproceduralblankandonespikedsample(additionlevel

100 ngL−1) were processed.Acceptable data correspond to

con-centration levels below method LOQs(from 5 to 20 ng L−1,

de-pendingonthecompound)inproceduralblanks,andrecoveriesin

therangefrom80% to120% LOQswerecalculatedasthe

concen-trationofeachcompoundprovidingasignaltonoise(S/N)ratioof

10 forthe Q1transitionwhileratiosbetweenqualification

transi-tions (Q2 andQ3 when available) andQ1 remain with± 30% of

averagevaluesobtainedwithinthecalibrationrangeofthe

proce-dure,Table1.Compoundsidentificationinnon-spikedsampleswas

based on retentiontime match withcalibration standards

(max-imum variation ± 0.1 min) and qualification (Q2, and Q3 when

available) toquantification(Q1) ionsresponseratios showing

dif-ferenceslowerthan± 30%comparedtothoseobtainedfor

calibra-tionstandards,Table1

3 Results and discussion

3.1 Optimization of SPE on-line connected to LC-QqQ-MS

Table 1summarizesretentiontimes,ionization mode,andm/z

valuesforprecursorandproductionsoftargetcompoundsandSSs

Althoughbothionizationmodeswereevaluated,ESI(+)produced

highersignaltonoise (S/N)responseratiosforall compounds

ex-ceptincaseofFosetylandAMPA

AtleasttwoMRMtransitionswereselectedpercompound.The

dwell time per transition was set at 100 ms for AMPA andGLY

(to enhance the detectability of both pesticides) and 20 ms for

therestofcompounds.Thegradientofmobilephasewasadapted

fromourpreviousstudydealingwiththedeterminationofAMPA,

GLY and Fosetyl in vegetal origin samples [17], considering the

delay of retention times induced by the on-line SPE

extraction-desorption steps Although alternative gradients to that reported

inSection 2.4canbe considered,baselineseparationbetweenthe

peaks of AMPA and Fosetyl is mandatory since both compounds

shareseveralproductionsandthem/zoftheirprecursors([M-H]−

ions) differ only in 1unit, Table 1.So, the cluster ofsignals

as-sociatedtothe[M-H]−ionofFosetyl(m/zvalues109and110, the

latterduetothenaturalabundanceof13C)mightleadtofalse

pos-itives forAMPA,whose precursorion([M-H]−)hasa m/z ratioof

110,unlessbothcompoundsarebaselineseparated

As regards theon-line SPEconcentration step, theflowrate of

water(phaseC,from0.5to2mLmin−1,during2.5min)employed

to loadstandardsand/or samples(up to0.45mL aliquots)inthe

on-lineconnectedSPEsorbentshowedalittleeffectintheirMRM

responses.Valuesbelow0.5mLmin−1turnedinapoor

repeatabil-ity;whilst compoundlossescan occuratloading flowratesabove

2mLmin−1 asaresultoftoolow equilibrationtimes.Eventually,

flowratesof0.5mLmin−1 (0–1min)and1mLmin−1 (1–2.5min)

wereemployed.Duringthisstep,targetcompoundsareretainedby

theanionic-exchangesorbent,whilstneutralsandcationicspecies flowthroughtowaste.Theaboveflowratesledtopressurevalues

of30and60PSIintheon-linecartridge

Forstandardspreparedinultrapurewater,responses ofall the compounds (peak areas without SScorrections) increased steady forvolumesofsamplefrom0.05mLto0.45mL(datanotshown); however,adifferentbehaviorwasnoticedforenvironmental sam-ples Fig 2 shows the slopes of calibration curves obtained for spiked aliquots of river and a commercial, bottled mineral wa-ter normalizedto thosemeasured forultrapure water.These two matriceswere selectedasrepresentativeofsoft(riverwater,Ca2 +

5mgL−1,Mg2 + 3mgL−1) andhard(mineral water,Ca2 + 86 mg

L−1,Mg2 + 30 mgL−1) waters. Forsample volumesof 0.080 and 0.160 mL, determination coefficients (R2) above 0.999 were ob-tainedfortheplotsofresponseversusconcentration,withsimilar slopesforthe3typesofwater.However,when0.240 mLof sam-pleareloadedintheon-linecartridge,significantreductionsinthe normalized slopes of severalcompounds, except NAG and MPPA, were found, Fig 2 Direct injection(0.05 mL volume aliquots) of samespikedsamplesintheanionicexchangecolumn,avoidingthe SPEstep,reflectedimportantvariationsintheslopesofcalibration curves corresponding to the river and the mineral water matrix compared to those obtained forultrapure water.Particularly, the responses ofGLU were enhanced significantly inboth water ma-trices compared to ultrapure water; moreover, GLY could not be detected inhard mineral waterandthe efficiencies ofMPPAand AMPAdetectionwere reducedinmorethan90%, Fig.S3.This in-formation,incombinationwithdatashowninFig.2,supportsthe factthat theon-lineSPEstep,contributesto reducethe complex-ityofthesampleandtoimprovethe performanceof compounds determination,avoidingtheentranceofneutralsandbasicspecies

inthechromatographiccolumn

3.2 Performance of SPE on-line combined with LC-MS/MS

Thelinearityofthemethodwasassessedwithcalibration stan-dardspreparedintherangefrom5ngL−1to5000ngL−1,atnine different concentration levels (5, 10, 20,50, 100, 250, 500,2000 and5000ngL−1,injected induplicate) After correction ofMRM responses withthose ofisotopically labelledstandards, R2 values above 0.998 were obtained, Table 2 Despite NAG and MPPA are structurally related to GLU, their retention times were closer to that of GLY; thus, the labelled analogue of GLY was used as SS

of these two compounds The reproducibility of responses (peak areawithoutSSscorrection)fora40ngL−1 standardinultrapure watervariedfrom2% forNAGto8% forAMPA(n =9 extraction-determination cycles within a 24-h sequence) Fig 3 shows the chromatogramforalow-level calibrationstandard(20 ngL−1 per compound)

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Fig 2 Slopes of calibration curves obtained for spiked aliquots of two different water samples normalized to those corresponding to ultrapure water Calibration range:

50 ng L -1 to 20 0 0 ng L -1 Error bars reflect standard deviations for the slope of calibration curves corresponding to each matrix

Table 2

Linearity, accuracy (recoveries for spiked samples, 80, 200 and 500 ng L −1 , with SD,%) and LOQs of the SPE on-line LC-QqQ-MS direct analysis method

Recovery (average with SD, n = 3 replicates) Compound R 2 (5–50 0 0 ng L −1 ) Ground water River water Tap water LOQs (ng L −1 )

80 ng L −1 200 ng L −1 500 ng L −1 80 ng L −1 200 ng L −1 500 ng L −1 80 ng L −1 200 ng L −1 500 ng L −1 Fosetyl 0.9994 71 (4) 77 (7) 122 (6) 115 (2) 91 (5) 95 (7) 118 (2) 92 (3) 126 (1) 5

AMPA 0.9993 102 (2) 88 (5) 112 (3) 83 (3) 80 (3) 86 (6) 101 (2) 89 (4) 106 (8) 5

GLU 0.9997 99 (3) 85 (3) 111 (1) 98 (1) 84 (5) 95 (8) 104 (3) 87 (1) 105 (5) 20

GLY 0.9999 93 (1) 85 (4) 106 (2) 103 (4) 87 (4) 88 (9) 101 (4) 86 (3) 114 (4) 10

NAG 0.998 87 (3) 99 (6) 101 (27) 79 (1) 92 (4) 97 (8) 83 (3) 93 (4) 141 (3) 5

MPPA 0.999 90 (2) 102 (6) 102 (14) 88 (3) 97 (5) 101 (9) 91 (2) 99 (4) 111 (2) 5

Theaccuracyofthemethodwasinvestigatedconsideringthree

water matricesand threeaddition levels (80 ngL−1,200 ng L−1

and 500 ng L−1) Obtained data are summarized in Table 2 In

general, recoveries varied in the range from 80% to 105%, with

associated standard deviations (SDs) below 8% In the particular

caseofFosetyl,recoveries forthedifferentmatricesshowed

aver-agepercentagesbetween71%and126%,withsimilarSDstothose

reported for the rest of compounds, Table 2 Finally, a recovery

around 140% wasobserved forNAGinone ofthesamplesspiked

at500ngL−1.TheLOQsoftheprocedure,calculatedasdescribed

inSection2.5,variedbetween5and20ngL−1.GLYandGLUwere

thespeciesdisplayingthehigherLOQs(10and20ngL−1,

respec-tively),duetotherelativelylowintensityofthequalification

tran-sitions (Q2andQ3)forthefirstpesticide (Fig.3D),andthe

pres-enceofaninterferingpeakintheQ2transitionofGLU(Fig.3C).In

ordertogetthesevalues,theLCinstrumentwasdailyconditioned

usingasolutionofcitricacid(5mM)ataflowof1mLmin−1,for

20 min, before installing the anionic exchange column No

mod-ifications were made in the hardware of the LC-QqQ-MS system

apart from (1) using an extended injector seat (0.5 mL volume,

made of PEEK) to accommodate the samplebefore being loaded

in theSPE cartridgeand(2)connectingthe outletofthe column

directly to the ESI source (avoiding the six-port valve of the MS

spectrometer).Theanalyticalcolumnwasusedformorethan1000

injectionswithoutlossesofperformance,andtheon-linecartridge

wasreplacedwhenincreasedpressurevalueswerenoticed(c.a

ev-ery300extraction-desorptioncycles)

The previous application ofanionic exchange chromatography,

considering similar LC-MS/MS conditions to those applied in the

currentresearch,achievedLOQsof100 ngL−1 forAMPA,GLYand

GLU for direct injection of 0.05 mL samples [18] Thus, the

on-line SPEstep showsa significant impact in the sensitivityofthe

analytical procedure, maintaining the simplicity ofthe direct

in-jection method, at the expense of a little increase in the

dura-tionoftheconcentration-determinationstep.LOQsattainedinthis

research are also lower than those attained for GLY and AMPA

considering SPE on-lineconnected to cationic exchange LC,

post-columnderivatizationandfluorescencedetection[21].Tothebest

Table 3

Summary of concentrations (ng L −1 ) for compounds above method LOQs in the set of 66 water samples

Positive samples (%) 88 38 12 Samples above 100 ng L −1 (%) 20 6 2

of our knowledge, the lowest LOQs achieved forGLY, AMPA and GLUinsurfacewatercorrespondedtothecombinationofFMOC–Cl compoundsderivatizationfollowedbyconcentrationofsamplesin reversed-phasetypesorbents,eitherintheoff-line[11],oron-line modes[10,12] The aboveapproachesreported LOQsintherange between0.7to 5 ngL−1.On the other hand,compounds deriva-tizationwastime-consumingandthesemethodsdonotcoverthe determinationof FosetylandMPPA,since they do notreact with FMOC–Cl

3.3 Occurrence of pesticides in surface water samples

Levels of target compounds in processed samples are given

as supplementary information, Table S3 Out of six investigated species,only AMPA, GLY andFosetyl were noticed Table 3 sum-marizes their maximum, medianand average concentrations, to-gether with the percentage of positive samples andthose above theenvironmentalthresholdof100ngL−1.Fig.S4showsthe chro-matogramscorresponding toquantificationandqualification tran-sitions of Fosetyl, AMPA andGLY fora non-spiked sample (sam-plingpointS9,2ndcampaign,TableS2)containingconcentrations

of these compounds in the range from 8.6 ng L−1 (Fosetyl) to 61.1ngL−1(AMPA).AMPAwasthecompoundshowingthehighest prevalence,withadetectionfrequencyof88%andamedian con-centrationof44.2ngL−1.Althoughrelativelylow,thisvalueis sim-ilar to those affecting the embryogenic development of amphib-ians[27].GLYshowedthehighestmaximumconcentration,witha

5

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Fig 3 MRM chromatograms for quantification (Q1, left) and qualification transitions (Q2 to Q3, center to right) of target compounds for a 20 ng L -1 standard prepared in ultrapure water A Fosetyl B AMPA C GLU D GLY E NAG F MPPA

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Fig 4 Seasonal variations in the concentrations of AMPA in sampling points affected (S1, S15) and not affected (S14 and average of S5, S6, S9 and S11) by municipal STPs

discharges of treated wastewater

level above 3000 ngL−1 inone of thestreams draining thehilly

vineyard area; however,the median value (26.9 ng L−1) andthe

percentageofpositivesamplesforthiscompound(38%)remained

below those obtained forAMPA This trendis coherent withthe

higherenvironmentalstabilityofthelaterspeciesversus the

par-ent herbicide [7], and potential formation of AMPA from

addi-tionalprecursormolecules.Finally,Fosetylwasthepesticide

show-ing the lowest medianconcentration (8.8 ngL−1) as well asthe

smaller percentage of samplesabove method´s LOQs(12%)

Glob-ally,residuesofAMPAandGLYfoundinthesetofprocessed

sam-ples stay 1–2 orders ofmagnitude below those reportedin

geo-graphicareas,suchasUSAandSouthAmerica,whereGLYresistant

crops are authorized [8,9] Onthe other hand,the detection

fre-quenciesandaverageconcentrationsofbothcompoundsarehigher

thanthosecorrespondingtotime-averagesamplesofsurfacewater

fromagricultureandresidentialareasinGermany[6]

As regardstheir geographicdistribution, AMPA and GLY were

ubiquitousinsamplesobtainedfromLimia river(samplingpoints

S16 and S17), whereas Fosetyl remained below method LOQs in

this area.Concentrations ofthe parentpesticide andits

degrada-tion product decreased frompoints S16 to S17 (Table S3), likely

due todilutionwiththe tributarychannel joiningthe main river

downstreampointS16,Fig.1.AMPAwasalsonoticedinmost

sam-ples from the two other investigated areas, except in those

ob-tainedfromagroundwaterspring(S10),whereallcompounds

re-mainedundetected.GLYwasmeasuredinsomesurfacewater

sam-ples fromthe vineyardandtheresidential areas,withthe higher

concentrationsfoundinsmallstreams

TheresiduesofAMPAquantifiedinsamplingpointsaffectedby

discharges oftreatedwastewater(codesS1 andS15)were higher

than in the rest of surface and spring water from the vineyard

andtheresidentialareas,TableS2.Moreover,theyincreasedfrom

spring(1stsamplingcampaign)tosummer(4thcampaign),asthe

flowofstreamsreceivingthedischargesfromSTPdecreased

signif-icantly,Fig.4.Ontheotherhand,theaverageresiduesofAMPAat

samplingpointsS5,S6,S9andS11,placedinalargedam

contain-ingapracticallyconstantvolumeof52cubichectometersofwater,

remainedconstantduringthefoursamplingcampaigns,Fig.4.This

temporal profileofconcentrationsiscoherentwiththeformation

ofAMPA notonlyfromGLY,butalsofromphosphatecompounds

usedintheformulationofdetergentsduringtreatmentof

munic-Fig 5 A, mass flows (g day -1 ) of GLY and AMPA in sampling point S17 (Limia river)

B, mass flow of AMPA (g day -1 ) in sampling points S2 and S4 (Avia river)

ipalwastewater,as it hasbeen alreadypointedout by other au-thors[11].Comparison ofAMPAlevels insamples fromthesame river(Tintoriver),downstreamandupstreamthedischargeofthe municipalSTP(samplingpointsS15andS14),inaresidentialarea, pointoutagaintothecontributionofthesefacilitiestotherelease

ofAMPAintheaquaticenvironment,Fig.4 Fig 5A shows the mass flow (g day−1) of AMPA and GLY at pointS17,duringthethreesamplingcampaigns.ThoseforAMPAin pointsS2andS4,duringfourcampaigns,arepresentedinFig.5B

7

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The on-linecombinationofSPE,usinga PEEK-linedstrong

an-ionic exchange cartridge, with an analytical column containing

samestationaryphasepermittedthesensitive,automated

determi-nationofsixZwitterionicpesticidesinenvironmentalwater

sam-ples, withoutanyprevious samplepretreatment, exceptfiltration

The procedureachievedLOQsbetween5 and20ngL−1,with

ac-ceptable accuracy values (calculated recoveriesfrom 71%to 126%

inallsamples,butone),andlimitedeffectofthesamplematrixin

theresponsesoftargetcompounds.Thus,itrepresentsasignificant

improvementcomparedtodirectinjectionmethodsusingsameLC

separation mechanism, and a much faster option than FMOC–Cl

based derivatization approaches Analysis of surface water

sam-ples,obtainedinaresidentialareaandtwoagriculturebasinswith

different typesofcrops,showed thepresence ofAMPA,GLY and,

lessoften,Fosetyl inthisenvironmental compartment.The lower

levels of AMPA andGLYwere noticedin springs ofgroundwater,

whilst thehigherconcentrationsofAMPAwereassociatedtoSTPs

affected streamsandrivers.Furtherstudiesshouldassessthe

ori-gin of AMPAnoticed in thiskindof watercourses, includingthe

searchofadditionalprecursorstoGLY

Declaration of Competing Interest

Theauthorsdeclarethattheyhavenoknowncompeting

finan-cialinterestsorpersonalrelationshipsthatcouldhaveappearedto

influencetheworkreportedinthispaper

CRediT authorship contribution statement

J López-Vázquez: Investigation,Methodology,Writing– review

& editing. L Pérez-Mayán: Investigation, Methodology, Writing –

review &editing. V Fernández-Fernández: Formal analysis,

Writ-ing – review&editing. R Cela: Conceptualization,Funding

acqui-sition. I Rodríguez: Conceptualization,Supervision,Funding

acqui-sition,Writing– originaldraft

Data availability

Datawillbemadeavailableonrequest

Acknowledgments

L.P.M thanks a FPU grant to the Spanish Ministry of Science

This study wassupported by Spanish Government andXunta de

Galiciathroughgrants PGC2018–094613-B-I00andED431C 2021/06,

respectively Both projects are co-funded by the EU FEDER

pro-gram We acknowledge Agilent for providing access to

LC-ESI-MS/MS instrumentationandtechnical assistancewithanionic

ex-changeLCseparations

Supplementary materials

Supplementary material associated with this article can be

found,intheonlineversion,atdoi:10.1016/j.chroma.2022.463697

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