Hindawi Publishing Co po a ion
BioMed Resea ch In e na ional
Volume 2013, A icle ID 674838, 23 pages
h p://dx.doi.o g/10.1155/2013/674838
Re iew A icle
Analy ical Me hodologies o he De e mina ion o
Endoc ine Dis up ing Compounds in Biological and
En i onmen al Samples
Zo aida Sosa-Fe e a, C is ina Mahugo-San ana, and José Juan San ana-Rod íguez
Depa amen o de Qu´
ımica, Uni e sidad de Las Palmas de G an Cana ia, 35017 Las Palmas de G an Cana ia, Spain
Co espondence should be add essed o Jos´
eJuanSan ana-Rod
´
ıguez; jsan [email protected]
Recei ed 25 Janua y 2013; Accep ed 25 Ma ch 2013
Academic Edi o : Ca los Bo ja Gue a He nandez
Copy igh © 2013 Zo aida Sosa-Fe e a e al. This is an open access a icle dis ibu ed unde he C ea i e Commons A ibu ion
License, which pe mi s un es ic ed use, dis ibu ion, and ep oduc ion in any medium, p o ided he o iginal wo k is p ope ly
ci ed.
Endoc ine-dis up o compounds (EDCs) can mimic na u al ho mones and p oduce ad e se e ec s in he endoc ine unc ions by
in e ac ing wi h es ogen ecep o s. EDCs include bo h na u al and syn he ic chemicals, such as ho mones, pe sonal ca e p oduc s,
su ac an s, and lame e a dan s, among o he s. EDCs a e cha ac e ised by hei ubiqui ous p esence a ace-le el concen a ions
and hei wide di e si y. Since he disco e y o he ad e se e ec s o hese pollu an s on wildli e and human heal h, analy ical
me hods ha e been de eloped o hei quali a i e and quan i a i e de e mina ion. In pa icula , mass-based analy ical me hods
show excellen sensi i i y and p ecision o hei quan i ica ion. This pape e iews ecen ly published analy ical me hodologies
o he sample p epa a ion and o he de e mina ion o hese compounds in di e en en i onmen al and biological ma ices by
liquid ch oma og aphy coupled wi h mass spec ome y. The a ious sample p epa a ion echniques a e compa ed and discussed.
In addi ion, ecen de elopmen s and ad ances in his ield a e p esen ed.
1. In oduc ion
The global p oduc ion o chemical p oduc s has inc eased in
he las decades, and al hough many o he p oduc s ha e
been bene icial o mankind, many o hem a e also oxic
because hey exhibi a long en i onmen al pe sis ence and
can accumula e wi hin o ganisms [1,2]. Cu en ly, many o
he p oblems o pollu ion a e due o in e mi en spillage
o hese subs ances in o he en i onmen . In addi ion o
hei oxici y, pe sis ence, and isk o bioaccumula ion, hese
subs ances also clea ly a ec biological p ocesses bo h in
plan s and in animals, including humans. The occu ence o
chemical compounds ha in luence he sexual de elopmen
o ish in English i e s was epo ed 15 yea s ago [3].
These exogenous subs ances ha in e e e wi h he endoc ine
sys em and dis up he physiologic unc ion o ho mones
a e called endoc ine-dis up ing compounds (EDCs). The
e ec s o na u al and syn he ic EDCs ound in he en i-
onmen include a dec eased spe m coun in human males
and an inc eased isk o b eas cance and ep oduc i e
abno mali ies in human emales [4–6]. The endoc inal and
ep oduc i e e ec s o endoc ine dis up ing compounds
maybeaconsequenceo hei abili y o(a)mimicna u al
ho mones, (b) an agonise hei ac ion, (c) al e hei pa e n
o syn hesis and me abolism, o (d) modi y he exp essions o
speci ic ecep o s. Figu e 1 shows a scheme o he endoc ine-
dis up ing ac ion.
Despi e he inc eased in e es in his ype o pollu an
ha has a isen in he scien i ic communi y and he ex ensi e
wo k pe o med o e he las wo decades, impo an aspec s,
including he need o p edic e ec s beyond he simply
obse ed ho monal ac ion ha is implica ed in he pa hogeny
o endoc ine- ela ed diseases, he le el o exhibi ion o he
gene al popula ion, he iden i ica ion o he h eshold le el
o he e ec , and he mechanisms o ac ion and hei ad e se
e ec s, ha e no been ho oughly in es iga ed [7]. In conclu-
sion, al hough a g ea deal o esea ch ela ed o he haza d
assessmen and egula ion o EDCs has been published, a
la ge numbe o unce ain ies emain wi h espec o hei
ac ions.
2BioMed Resea ch In e na ional
Recep o
Cell inside
Response
Ho mone
No mal ho mone binding
(a)
Ho mone
Endoc ine
dis up e
Unde esponse (D)
O e esponse (D)
Inhibi ed esponse (C)
Endoc ine dis up ing ac ion
Iden ical
esponse (A)
An agonized esponse (B)
(b)
Figu e 1: Scheme o he endoc ine dis up ing ac ion: (A) mimic na u al ho mones, (B) an agonize hei ac ion, (C) al e hei pa e n o
syn hesis and me abolism, o (D) modi y he exp essions o speci ic ecep o s.
Many EDCs a e no cu en ly co e ed by exis ing egu-
la ions. A numbe o in e na ional o ganisa ions ha e made
se e al a emp s o es ablish a consensus ela ed o EDCs;
howe e , henumbe o amilieso so-calledendoc ine
dis up ing pollu an s inc eases each yea . The aim o his
wo k is o p o ide he scien i ic communi y wi h a se o
amilies o chemical compounds o which special a en ion
should be de o ed [8].
Al hough many na u al and syn he ic chemicals a e
widely conside ed o be EDCs, nume ous chemicals p esen
in he en i onmen s ill emain uniden i ied and a e con-
side ed po en ial EDCs. Mo eo e , many new chemicals a e
con inually being p oduced in esponse o needs in a ious
indus ial sec o s, and e idence o he endoc ine dis up ing
compoundsac i i ieso someo hesecompoundsiso en
con o e sial.
To da e, se e al s udies ha e demons a ed he nega i e
e ec s o EDCs on wildli e and human heal h, which seem
o occu e en in cases o ace-le el EDCs. G ea a iabili y,
howe e , has been obse ed in chemical s uc u es o EDCs
ha possess di e se cha ac e is ics wi h simila an iand o-
genic and s e oidogenesis ac i i ies [9–16]. Because o he
la ge a ie y o suspec ed EDCs, humans and animals a e
mos likely exposed no o a single agen , bu a he o a
mix u eo mul ipleendoc ine-dis up ingagen s.
Mos EDCs a e syn he ic o ganic chemicals (xenobio ics)
in oduced in o he en i onmen by an h opogenic inpu s;
howe e , hey can also be na u ally gene a ed es ogenic
ho mones (e.g., es one o 17𝛽-es adiol). Sou ces o EDCs
include na u al and syn he ic ho mones, pe sonal-ca e p od-
uc s, pes icides, ph hala es, alkylphenol e hoxyla e su ac-
an s, lame e a dan s, dioxins, coplana polychlo ina ed
biphenyls (PCBs), pa abens, bisphenol A, and o gano ins
[17]. Figu e 2 shows hechemicals uc u eo someo hese
compounds mo e commonly ound in en i onmen al and
biological samples. A common cha ac e is ic o all o hem is
ha hey con ain a leas one a oma ic moie y in hei molec-
ula s uc u e. Thus, hei hyd ophobic p ope ies migh
comp ise an impo an cha ac e is ic o hei beha iou .
The ac ha EDCs a e ubiqui ous in he en i onmen ,
especially in aqua ic ecosys ems, has aised conce n. Many
esea che s ha e shown ha was ewa e ea men plan s
(WWTPs) a e majo con ibu o s o he p esence o EDCs
in he en i onmen , whe e hey en e ia domes ic and
indus ial discha ges [18–20]. WWTPs achie e only pa ial
emo al o EDCs. As a consequence, hese compounds ha e
been ound in he e luen s om WWTPs, and hey can
he e o e each he su ace and he g oundwa e .
Because o he nonpola and hyd ophobic na u e o
many EDC, ha hey can be abso bed on o pa icula e
ma e ials. This beha iou sugges s ha he gene al e ec
o was ewa e ea men p ocesses should be o concen a e
o ganic pollu an s in he sewage sludge, whe eas mechanical
sepa a ion echniques, such as sedimen a ion, should esul
in signi ican emo al o o ganic pollu an s om he aqueous
phase o p ima y and seconda y sludges. As a esul , he
ea ed was ewa e is discha ged ela i ely ee o EDCs;
howe e , he EDCs a e abso bed in o sewage sludge, which
couldcons i u eanewsou ceo pollu ion.Thesludge om
WWTPs can be applied o ag icul u al ields as a e ilise .
Cu en legisla ion egula es he ag icul u al use o sewage
sludge based only on he concen a ion o oxic hea y me als
and nu ien s. Howe e , ollowing he measu es ha he
Eu opean Commission (EC) began o implemen in 1999, he
hi d d a o a u u e Sludge Di ec i e con ained a p oposal
o place limi s on se e al o ganic con aminan s [21,22].
The unme abolised compounds p esen in he manu e
o hei biologically ac i e me aboli es may mo e om he
manu ein he ields o heg oundwa e ande en uallyen e
su ace wa e , such as i e s and lakes, whe e hey can a ec
aqua ic o ganisms. They may pe sis in solid en i onmen al
ma ices o a p olonged pe iod. Thei pe sis ence depends
on hei pho os abili y, binding and adso p ion capaci y,
deg ada ion a e, and leaching a e in o he wa e . Thei
accumula ion is due o hei mode a ely high oc anol-wa e
pa i ion coe icien (log 𝐾ow =3–5) [23].
Depending on he EDC, hei e ec s on bio a ha e been
obse ed a EDC concen a ions as low as 0.1 ng⋅L−1 [20]. The
BioMed Resea ch In e na ional 3
S e oid ho mones
Es one
1,3,5(10)-Es a ien-3-ol-
17-one
HO
H
CH3O
Es adiol P oges e one
4-P egnene-3,20-dione
Tes os e one
17b-Hyd oxyand os -4-ene-3-
one
H
H
H
Endoc ine dis up ing compounds
3,17diol
Pe sonal ca e p oduc s (PCPs)
T iclosan
5-Chlo o-2-(2,4-
dichlo ophenoxy)phenol
T icloca ban
N-(4-Chlo ophenyl)-N-(3,4-
dichlo ophenyl) u ea Me hyl pa aben
Benzophenone-3
2-Hyd oxy-4-me hoxy
benzophenone
Cl
OH
O
N
H
C
OH
O
Cl
N
H
Cl
Cl
Cl
OO
CH3
OH
Cl
O
Alkylphenol polye hoxyla es (APEOs)
Bisphenol A Nonylphenol 4-Oc ylphenol-monoe hoxyla e
Flame e a dan s
TBBPA
A
HBCD
Hexab omocyclododecane
BDE-100
e he
BDE-209
CH3
CH3
HO
H
H
OH
O
H
CH3
H
H
CH3
CH3
O
CH3H
CH3
OH
HH
O
HO C
CH3
OH
O
OH
OH
H3C
CH3
H3C
OH
HO B B
B B
B
B
B
B
B
B
B
B
B B
B
B B
OB
B
B
B
B
B
B
B
O
Decab omodiphenyl e he
(17𝛽)-Es a-1,3,5(10)- iene-
1,2,5,6,9,10-
OCH3
2,2󳰀,3,3󳰀,4,4󳰀,5,5󳰀,6,6󳰀,-
2,2󳰀,4,4󳰀,6-Pen ab omodiphenyl
2,2󳰀,6,6󳰀-Te ab omobisphenol
Figu e 2: Chemical s uc u e o EDCs mo e commonly ound in en i onmen al and biological samples.
de e mina ion o hese chemicals is equi ed o allow hei
en i onmen al impac o be assessed. In ecogni ion o hese
conce ns, p essu e o u he de elop ad anced was ewa e
ea men me hods, such as ozona ion and ac i a ed ca bon
ea men o b oad applica ions in municipal was ewa e
ea men , has inc eased in Eu ope.
In his con ex , we need o expand ou knowledge abou
he occu ence, anspo , and a e o all hese con aminan s
in he en i onmen al and in biological samples. Thei analysis
ep esen s a di icul ask because o he high complexi y o
hema icesanalysedandbecauseo heusuallylowconcen-
a ion (ng⋅L−1)a which he a ge compoundsa ep esen
in such samples. In addi ion, bio ic samples a e complex
ma ices ha con ain la ge amoun s o possible in e e ing
compounds ha necessi a e he use o ex ensi e ex ac ion
and clean-up p ocedu es o ob ain ex ac s amenable o
4BioMed Resea ch In e na ional
analysis. As a esul , he eliable quan i ica ion o EDCs in
bo h en i onmen al and biological samples ep esen s an
eno mous challenge o analy ical chemis s.
As a consequence, one o he majo ends in analy ical
chemis y is he de elopmen o as and e icien p ocedu es
o he aceanalysiso a ge andnon a ge o ganiccom-
pounds in complex ma ices.
2. Ad anced Ins umen a ion
In ecen yea s, ad ances in ins umen a ion ha e esul ed
in signi ican p og ess in he de ec ion o EDCs, he unam-
biguous iden i ica ion o hei s uc u es, and he de e mi-
na ion o hei amoun . A numbe o analy ical me hods
ha e been epo ed in he li e a u e o he analysis o he
a ge compounds. High-pe o mance liquid ch oma og a-
phy (HPLC) is he dominan mode n analy ical echnique
employed o he analysis o hese ypes o compounds. The
imp o emen s achie ed du ing he las ew yea s in e ms o
sensi i i y a e mos ly due o he de elopmen o hyphena ed
ch oma og aphy-mass spec ome y echniques, which a e
oday he me hods o choice o he de e mina ion o ace
o ganic analy es in en i onmen al and biological samples.
Mass spec ome y (MS) is he one o he mos aluable
de ec ion echniques because i p o ides in o ma ion o he
molecula s uc u e o he compounds and because i is
highly sensi i e and selec i e. The combina ion o ch o-
ma og aphy and MS can sepa a e a mix u e in o i s indi idual
componen s and subsequen ly analyse each compound in he
mix u e bo h quali a i ely and quan i a i ely. Fo quan i i-
ca ion, he selec i e-ion mode (SIM) o MS can be used o
achie ehighsensi i i y.Thehugein e es in heapplica iono
LC-MS echniques has signi ican ly s imula ed de elopmen s
and imp o emen s in mass-analyse echnology.
Howe e , when highly complex ma ices a e in es iga ed,
iple quad upole (QqQ) MS is equi ed o imp o e he
de e mina ion selec i i y and he unequi ocal iden i ica ion
o he a ge analy es [24]. These ins umen s, which used
in andem MS, a e able o isola e he molecula ion o he
compound o in e es in he i s s age o he mass analyse
and ob ain selec i e p ecu so -p oduc ion ansi ions when
ope a ed in selec ed eac ion moni o ing (SRM) mode. The
mos in ensi e agmen ion om he p ecu so ion is used
o quan i ica ion. A less sensi i e seconda y ansi ion is
used as he second c i e ion o con i ma ion pu poses.
QqQ ea u es a wide linea ange o a leas h ee o de s o
magni ude.
Recen ly, mo e ad anced MS echnologies, such as ime-
o - ligh (TOF-MS) o linea ion ap (LIT-MS), ha e been
in oduced and ep esen a powe ul new iden i ica ion ool.
New hyb id quad upole- ime-o - ligh mass spec ome y
(Qq-TOF-MS) allows he acquisi ion o ull-scan p oduc -ion
spec a, which p o ide he accu a e mass o he p oduc ion.
Based on he p oduc -ion spec a, he s uc u al elucida ion
o unknown compounds as well as he iden i ica ion o a ge
compounds can be achie ed wi h a much g ea e deg ee o
ce ain y [25].
A he same ime, demand o high- h oughpu analysis
is g owing due o an inc easing numbe o samples, and
sho ening o he analy ical un imes is o en equi ed.
Th ee main mode n app oaches in HPLC me hods enable he
educ ion o analy ical ime wi hou comp omising esolu-
ion and sepa a ion e iciency: he use o monoli h columns,
liquid ch oma og aphy conduc ed a high empe a u es, and
liquid ch oma og aphy a ul a-high p essu es using columns
packed wi h sub-2-mic on pa icles [26,27].
The use o a monoli h-so ben -based ins ead o po ous-
pa icle-based column packings has become popula in he
ield o bioanaly ical applica ions o e he pas ew yea s.
Monoli hs can accep high low a es (up o 10 mL min−1)in
con en ional column leng hs wi hou gene a ing high back-
p essu es, which is hei main ad an age. The e iciency and
esolu ion o monoli h so ben s a e compa able o hose o
silica pa icles wi h a diame e o 3 𝜇m. Monoli hic ods a e
p epa ed by sol-gel echnology, which enables he o ma ion
o a highly po ous ma e ial ha con ains bo h mac opo es
and mesopo es in i s s uc u e. Much g ea e low a es can
be used and he esolu ion o he monoli h od column
is insigni ican ly less a ec ed by pa icula e ma e ials. In
addi ion, he column back-p essu e emains low. Ano he
p ac ical ad an age is he sho - ime equi ed o column
equilib a ion when a mobile-phase g adien is used. Howe e ,
monoli h columns also su e se e al d awbacks. One is
he limi ed numbe o comme cially a ailable s a iona y
phases (C8, C18, and plain silica only). Ano he is he in e -
nal diame e s o monoli h columns (i.e., 4.6 mm, 4.0 mm,
and 100 𝜇m in e nal diame e s a e ypical; howe e , 2.0
and 3.0 mm columns ha e no , as ye , been manu ac u ed
in all common column leng hs). These wo disad an ages
educe hei applica ion domains subs an ially. La ge in e nal
column diame e s, which a e mo e eadily a ailable in all
column leng hs, a e no ully compa ible wi h MS (mass
spec ome y) and induce a high consump ion o o ganic
sol en , especially wi h low a es as high as 10 mL⋅min−1.
Finally, monoli hs made o silica possess limi ed chemical
s abili y (pH ange 2–8) [26,28,29], which, again, limi s hei
applicabili y.
Ele a ed empe a u es in high- empe a u e liquid
ch oma og aphy (HTLC) (𝑇>60
∘C) can also be used
o pe o m apid analysis using s anda d column leng hs.
In HTLC, in he iscosi y o he mobile phase iscosi y
is educed because o highe empe a u es, which esul s
in heme hod’sp ima yad an ageo as e analyses.The
e iciency, he mass ans e , and he op imal eloci y inc ease
simul aneously wi h inc easing empe a u e, which enables
he use o high mobile-phase eloci y. The low iscosi y and
he high di usi i y o a mobile phase a high empe a u es
p oduce much lowe mass ans e esis ance; in addi ion,
o ganic sol en consump ion may also be educed, which
is consis en wi h he p inciples o “g een” ch oma og aphy.
Howe e , e en wi h he a o emen ioned ad an ages, HTLC
is no ou inely used because i has some d awbacks.
Fi s , he limi ed a ailabili y o s able high- empe a u e-
esis an packing ma e ials is p oblema ic. Second, uns able
compounds may deg ade [30,31].
BioMed Resea ch In e na ional 5
The as es g owing end in ch oma og aphy con inues o
be he use o ul a-high-pe o mance liquid ch oma og aphy
(UHPLC). UHPLC uses sho columns and small-diame e
pa icles (sub, 2 𝜇m) in he s a iona y phase, which allows
highe p essu es and, ul ima ely, na owe LC peaks (5–10 𝜇s
wide). In addi ion o p o iding na ow peaks and imp o ed
ch oma og aphic sepa a ions, UHPLC d ama ically sho ens
analysis imes, o en o 10 min o less [26,27,30–33]. Because
o he e y na ow peaks p oduced by UHPLC (i.e., peak
wid hs on he o de o a ew seconds), he coupling o a
UHPLC o an MS de ice wi h a apid acquisi ion a e is
c i ical o ensu e high e iciency.
The ion supp ession/enhancemen e ec s play an impo -
an ole in LC-MS quan i ica ion, and he ex en o hese
e ec s needs o be quan i a i ely assessed [34,35]. The ion
supp ession and ma ix e ec s can cause se e e p oblems
wi h he quan i ica ion in ace analyses. To elimina e any
possible a ia ions du ing he ionisa ion p ocess and he
mass analysis, such as he ion supp ession/enhancemen , he
con amina ion o he ion sou ce o he mobile phase, ex ac-
ion losses, o any o he unp edic able e ec s, an in e nal
s anda d mus be used. Because hese ma ix e ec s migh
de imen ally a ec impo an me hod pa ame e s (e.g., he
limi o de ec ion (LOD), he limi o quan i ica ion (LOQ),
he linea i y, he accu acy, o he p ecision), sample p e-
ea men s ha in ol e isola ion o he analy es, pu i ica ion
o he ex ac s, and p econcen a ion a e equi ed [36].
3. Sample P epa a ion
When de eloping analy ical me hods o de e mined EDCs,
bo h he ypically e y low concen a ion a which hese
compounds occu in en i onmen al and biological samples
and he complex ma ix composi ion should be aken in o
accoun . Bo h analy e isola ion and p econcen a ion p oce-
du e a e necessa y o maximise he eco e y o he analy e.
In addi ion, EDCs concen a ion migh luc ua e bo h in
ime and in space, and s anda ds (e.g., deu e a ed one) and
e e ence ma e ials a e no eadily a ailable.
Sample p epa a ion and clean-up a e necessa y o h ee
main easons: o emo e in e e ences ha would o he wise
a ec he de e mina ion o he analy es; o en ich he a ge
compounds o de ec able concen a ions; and o pe o m
sol en swi ching o he desi ed sol en condi ions used o
ins umen al de ec ion.
Samples ob ained om biological ma e ials a e usually
no di ec lycompa iblewi hHPLCanalysesbecauseo
hei complexi y and p o ein con en . Biological samples a e
p oblema ic due o he i e e sible adso p ion o p o eins in
he s a iona y phase, which esul s in a subs an ial loss o
column e iciency and an inc ease in backp essu e [37].
To ob ain high eco e ies and minimise in e e ence, he
de e mina ion o hese pollu an s equi es ex ac ion and
clean-up s eps p io o de ec ion. The sample p epa a ion
s eps o en cons i u e he mos ime- and labou -in ensi e
pa s o he analy ical p ocess. A scheme ha e lec s he o al
analy ical me hod o complex biological and en i onmen al
samples should be simila o ha shown in Figu e 3.
The sample ex ac ion pe o med p io o ins umen al
analysis has se e al goals [38,39]. Liquid-liquid ex ac ion
(LLE) and solid-phase ex ac ion (SPE) a e he adi ional
echniques used o ex ac o ganic compounds om liquid
samples [40,41]. SPE o e s some ad an ages o e LLE, such
as imp o ed selec i i y, speci ici y and ep oducibili y, lowe
o ganic sol en consump ion, sho e sample p epa a ion
ime, easie ope a ion, and he possibili y o au oma ion. In
heSPEp ocedu e, hechoiceo so ben isc i icalbecause
i con ols selec i i y, a ini y, and capaci y. Based on he
cha ac e is ics o he a ge compounds, such as hei pola i y,
and he sample ma ix, di e en SPE so ben s can be chosen.
SPE ep esen s a b oad ield wi h nume ous applica ions and
has o en been he subjec o de ailed s udies and e iews
[37,41–45].
Much p og ess has been made ecen ly owa d imp o -
ing adso ben ma e ials; he mos ele an de elopmen s
a e ad anced ma e ials, such as es ic ed-access ma e ials
(RAMs) and molecula ly imp in ed polyme s (MIPs). RAMs
a e designed speci ically o he emo al o mac omolecules
based on he size-exclusion mechanism, whe eas MIPs a e
polyme -based ma e ials ha a e o med du ing u ilisa ion
o he empla emolecules ha playa olein a ge -compound
ecogni ion. Because o hei selec i i y, hese ma e ials ha e
ound applica ions p ima ily in a eas whe e a la ge in e e ing
subs ance is p esen in he complex ma ix [41].
The de elopmen o online SPE con igu a ion coupled
wi h LC p o ides se e al ad an ages, including a educ ion
o he numbe o sample handling s eps equi ed, he elimi-
na ion o he a ge loss by keeping he ca idge om d ying,
which esul s in an imp o ed eco e y and a educ ion o he
analysis ime, and he minimisa ion o he olume o o ganic
sol en s consumed du ing each analysis. In gene al, online
SPE-LC consis s o a small p ecolumn placed in a six-po ,
high-p essu e swi ching al e. Du ing injec ion, he sample
is p econcen a ed on a p ecolumn wi h small dimensions
o a oid band b oadening in space; his column is p essu e-
esis an . The analy es a e elu ed on o he analy ical column
by al e swi ches [41].
In mul i esidue analyses, he g ea es di icul y is he
selec ion o he expe imen al condi ions o he ex ac ion.
The op imisa ion o SPE condi ions mus lead o a comp o-
mise because he compounds exhibi di e en physicochem-
ical p ope ies. The e a e some disad an ages associa ed wi h
SPE o de e mina ion o EDCs in en i onmen al samples:
SPE can be labo ious and ime consuming i he sample
olumes a e la ge (100–1000 mL pe sample), and unwan ed
ma ix componen s, which a e ypically p esen a much
highe concen a ions han he analy es o in e es in ma ices
such as was ewa e , coex ac wi h he analy es.
The demand o educe he sol en olumes and a oid
he use o oxic o ganic sol en s has led o subs an ial
e o s o adap exis ing sample p epa a ion me hods o
he de elopmen o new app oaches. Consequen ly, du ing
he las decade, esea che s ha e made p og ess owa ds
he de elopmen o mo e e icien ex ac ion and clean-up
echniques; he mos ecen endencies ha e been owa ds
au oma ion h ough coupling o sample p epa a ion uni s
and de ec ion sys ems; he applica ion o ad anced so ben s;

6BioMed Resea ch In e na ional
Liquid ch oma og aphy
LC
Liquid
samples
PLE
UAE
MAE
SFE
UHPLC
Linea quad upole
ion ap
TOF
SPE
SPME
Sampling
Solid
samples
Liquid
samples
Solid
samples
Ex ac ion
Ex ac ion
Ex ac ionEx ac ion LPME
Mass spec ome y
En i onmen al samples
Biological samples
Analy ical me hod o biological and en i onmen al samples
Ion ap TOF
quad upole
TOF
quad upole LIT
LLE (ace oni ile
e hyl ace a e)
Figu e 3: Scheme o he analy ical me hod o he de e mina ion o EDCs in biological and en i onmen al samples.
and he applica ion o g eene app oaches, such as educed-
sol en echniques. Minia u isa ion has been a key ac o
in he app oaches de eloped o sa is y hese objec i es.
Mic oex ac ion echniques allow high-en ichmen ac o s
and minimise sol en consump ion, which a oids en i-
onmen al pollu ion. These echniques include solid-phase
mic oex ac ion (SPME), s i -ba so p i e ex ac ion (SBSE),
and liquid-phase mic oex ac ion (LPME) app oaches o
liquid samples [38].
SPME is a mode n equilib ium ex ac ion me hod. A
used-silica ib e coa ed wi h a polyme ic phase is usually
u ilised in SPME [46]. Typically, SPME me hod de elopmen
equi es op imisa ion o he equilib a ion condi ions o each
compound, which can make he de elopmen mo e di icul .
BioMed Resea ch In e na ional 7
SPME has shown some ad an ages o e SPE: he sample
olume is dec eased; he p ocedu e is simple because i
inco po a es sampling, ex ac ion, concen a ion, and sample
in oduc ion in o a single s ep; and indi idual ib es can
be used o mul iple ex ac ions. Howe e , SPME also s ill
exhibi s limi a ions, such as he sho ib e li e ime, he
high cos , agili y, and he occu ence o ca y-o e e ec s.
Fu he mo e, i lacks selec i i y in he ex ac ion o analy es
in complex ma ices [47–50].
In an au oma ed e sion o SPME, in ube SPME, an
open ubula used-silica capilla y wi h an inne su ace
coa ing, has been used as he ex ac ion de ice; his echnique
is simple and can easily be coupled online wi h HPLC,
[51,52]. Analy es in liquid samples a e di ec ly ex ac ed
andconcen a edon o hes a iona yphaseby epea ed
d aw/ejec cycles o s a ic so p ion o he sample solu ion.
The au oma ion o he ex ac ion p ocess educes he analysis
ime compa ed o ha equi ed o SPE and can also p o ide
be e accu acy, p ecision, and sensi i i y han o line manual
echniques.
This echnique can o e come p oblems ela ed o he use
o con en ional ib e SPME, such as agili y, low so p ion
capaci y, and bleeding o hick- ilm coa ings o he ib es.
The main disad an age o his echnique is ha i equi es
e y clean samples because he capilla y is easily blocked and
he sample pu i ica ion equi es special ins umen a ion and
ope a o expe ience.
Bal ussen e al. [53] in oduced a new and imp o ed
sample p epa a ion echnique based on he same p inciples
as SPME: s i -ba so p i e ex ac ion (SBSE). These s i ba s,
called Twis e s (GERSTEL), a e coa ed wi h a polydime hyl-
siloxane (PDMS) laye , which is he mos widely used so p i e
ex ac ion phase. Al hough he basic p inciples o SPME and
SBSE a e gene ally iden ical and use he same ex ac ion
phase, heamoun o PDMSis50–250 imesg ea e han
ha used in SBSE. This ea u e allows he p econcen a ion
e iciency o be imp o ed compa ed wi h SPME, which is he
main ad an age o SBSE [54,55].
Al hough SPME has been he echnique mos widely
used, in ecen yea s, liquid-phase mic oex ac ion (LPME)
app oaches ha e a ac ed inc easing in e es . LPME can be
conside ed a minia u ised o m o LLE and o e comes many
o i s disad an ages while equi ing minimal amoun s o
sol en [38,56]. In his p ocedu e, only a small amoun o
o ganic sol en is used o he ex ac ion om an aqueous
phase ha con ains he analy es o in e es . LPME is simple o
use, is gene ally apid, and is cha ac e ised by i s a o dabili y
and elianceonwidelya ailablema e ials[38]. Resea ch
on his echnique began wi h esea che s who used small
d ople s o o ganic sol en s suspended om he ip o a
mic osy inge needle. Howe e , new app oaches ha e been
de eloped oanalysecompoundso adi e en na u eand
o achie e la ge en ichmen ac o s using ela i ely sho
ex ac ion imes [38,56].
Basic schema ic illus a ions o he p inciples o he
sepa a ion app oaches used o biological and en i onmen al
liquid samples a e shown in Figu e 4.
As p e iously men ioned, due o he high oc anol-wa e
pa i ion coe icien and he low biodeg adabili y o many
EDCs, hey could be ound bound o sewage sludge and
o issue samples. To da e, mos o he epo ed analy ical
me hods o he de e mina ion o hese selec ed con ami-
nan s in he en i onmen ha e been ocused on aqueous
ma ices (e.g., su ace wa e and sewage wa e ). Nume ous
me hodologies ha e been de eloped o analysis o such
con aminan s in solid ma ices, wi h sedimen s ha ing been
in es iga ed sligh ly mo e han sewage sludge, mos likely
because o he complexi y o he la e ma ix. In addi ion o
he pollu an s o in e es , sewage sludge con ains a numbe o
o he componen s ha po en ially in e e e in he analysis o
he pollu an s o in e es ; hei emo al om he sample using
an es ablished ex ac ion and clean-up p ocedu e is he e o e
c i ical.
Fo he analysis o biological samples, he samples a e
gene allyw ungands o eda −18∘C be o e analysis. A e he
samples ha e been spiked a he desi ed le el, hey a e mixed
and homogenised in an o ganic sol en , such as ace oni ile,
and hensonica edandcen i uged.
In ecen yea s, ex ac ion me hods ha e usually been
based on liquid pa i ioning wi h ul asonic ex ac ion (USE),
mic owa e-assis ed ex ac ion (MAE) o wi h he mo e
ad anced echniques o p essu ised liquid ex ac ion (PLE),
o supe c i ical luid ex ac ion (SFE), which ha e eplaced
Soxhle ex ac ion [57,58]. These echniques o e impo an
bene i s, such as a sho ex ac ion ime, dec eased sol en
consump ion, and dec eased sample handling, in compa ison
o he adi ional Soxhle ex ac ion p ocedu e. The mos
e ec i e me hod o he clean-up o ex ac s o solid samples
ha con ain EDCs esidues has p o ed o be solid-phase
ex ac ion (SPE).
Ul asound-assis ed ex ac ion (UAE) in ol es he appli-
ca ion o ul asound adia ion o he samples in a wa e ba h
o using o he de ices [59–61]. The ypical ex ac an s a e
me hanol,e hanol,ace oni ile,andace onein hemL ange
o olume, and he sonica ion imes lie in he ange o 2–
120 min. A e sonica ion, he ex ac ed analy es a e sepa a ed
om he ma ix by acuum il a ion o cen i uga ion. The
p ocess is epea ed wo o h ee imes o achie e highe
ex ac ion e iciencies; he ex ac s a e hen ecombined,
and a clean-up p ocedu e wi h SPE ca idges is applied
p io o he analysis. The main disad an age o UAE is
poo ep oducibili y because o he lack o uni o mi y in
he dis ibu ion o ul asound ene gy, oge he wi h low
selec i i y and limi ed sample-en ichmen capabili ies. UAE
is no easily au oma ed and is no sui able o ola ile analy es.
A isk in he applica ion o UAE o o ganics is he po en ial
deg ada ion o he analy es ha may occu upon sonica ion
[62]. A numbe o pape s ha e been published dealing wi h
ul asound-assis ed ex ac ion o a ious EDC esidues [63–
67].
Mic owa e-assis ed ex ac ion (MAE) can be used o
imp o e he e iciency o he ex ac ion p ocess. In MAE,
mic owa eene gyisused ohea sol en sincon ac wi h
solid samples and o pa i ion analy es om he sam-
ple ma ix in o he sol en ( he ex ac an ). In p inciple,
only samples o sol en s ha con ain dipola ma e ials o
mic owa e abso ben s a e a ec ed by mic owa es. Since i s
ini ial de elopmen , MAE has become a byble al e na i e o
8BioMed Resea ch In e na ional
Solid d op mic oex ac ion (SD-LPME)
S i ba so p i e ex ac ion (SBSE)
In ube solid-phase mic oex ac ion (in ube SPME)
Solid-phase ex ac ion (SPE) Solid-phase mic oex ac ion (SPME)
O ganic d op
Ice ba h
D ople
collec ion
S i ba
Aqueous sample
D ople
collec ion
Aqueous
sample
+
ex ac an
Cen i uga ion
Dispe san
Cloudy
solu ion
Ma ix
Analy e
Elu ion
Rinsing
Sample
addi ion
Condi ioning
Sample
Capilla y
column
LC pump
LC column De ec o
Sample
pump Wash
pump
Was e
A. load posi ion (ex ac ion) B. injec posi ion (deso p ion)
Capilla y
column
LC pump Sample
pump Wash
pump
Was e
LC column De ec o
Analy es
Ex ac ion Deso p ion
Dispe si e liquid-liquid mic oex ac ion (DLLME)
Sepa a ions app oaches o liquid samples
S i ba
M
a ix
An
Figu e 4: Schema ic illus a ions o sepa a ion app oaches o biological and en i onmen al samples.
BioMed Resea ch In e na ional 9
con en ional me hods because i o e s subs an ial imp o e-
men s o e o he sample-p epa a ion echniques: o exam-
ple, sho e ex ac ion imes ( he sol en is hea ed apidly;
an a e age ex ac ion akes 15–30 min), he use o smalle
amoun s o sol en (be ween 10–30 mL), and inc eased sam-
ple h oughpu (mul iple samples can be ex ac ed simul ane-
ously) [68]. The empe a u e, he ex ac ion ime and powe ,
he sol en olume, and he concen a ion o di e en sol en
mix u es a e he mos common pa ame e s o be op imised.
The numbe o pape s ha ha e epo ed he use o MAE
has he e o e inc eased conside ably [69–72]. MAE sys ems
can ope a e in wo modes: open ( ocused MAE) o closed
(p essu ised MAE) essels. In he la e de ices, he sol en
is hea ed and p essu ised. Addi ional clean-up o he ex ac
o he samples is gene ally necessa y p io o analysis, and
MAE is no amenable o au oma ion (online ex ac ion and
de ec ion).
The main ad an age o MAE is mos likely i s wide
applicabili y o he as ex ac ion o analy es, including he
ex ac ion o EDCs om soils and sedimen s [73–76]and
om animal issues [77,78]. Al hough some examples o
hyphena ed MAE-based sys ems ha e been desc ibed [79,
80], he di icul y in in eg a ing an MAE de ice in o a low
sys em ep esen s one o he main sho comings o his
echnique.
P essu ised liquid ex ac ion (PLE), also called accele -
a ed sol en ex ac ion (ASE), is a new ex ac ion echnique
ha p o ides he oppo uni y o educe he ex ac ion ime
and he sol en consump ion (15–30 mL) wi h a high le el
o au oma ionand oob ainbe e eco e ies han hose
achie ed wi h he classical ex ac ion echniques h ough
he use o highe empe a u e and/o highe p essu es [70,
81,82]. These aspec s esul in an inc eased e iciency and
an inc eased a e o ex ac ion. In a con en ional PLE,
he sample, which is ypically dispe sed in a d ying o
ine so ben , such as sodium sulpha e, hyd oma ix, o
dia omaceous ea h, is packed in o a s ainless-s eel cell and,
a e he cell has been inse ed in o a closed low- h ough
sys em, he sample is ex ac ed wi h he selec ed sol en a
empe a u es g ea e han i s a mosphe ic boiling poin . This
echnique o e s he ad an age ha only wo a iables need
o be op imised: he ex ac ion ime and he empe a u e.
Mo eo e , PLE p o ides cleane ex ac s han Soxhle and
ul asonic ex ac ion, which esul s in educed backg ound
noise du ing he subsequen de e mina ion; he educ ion o
backg ound noise is especially impo an in LC-MS analysis
due o ion-supp ession e ec s. The main limi a ions o PLE
a e ha he selec i i y owa ds he analy es du ing ex ac ion
is no as high as migh be desi ed and ha many in e e en s
may be coex ac ed, depending on he ype o sample. O he
disad an ages include dilu ion o he analy es, especially
when a la ge numbe o cycles a e used [83], and he high ini-
ial cos o hese ex ac ion sys ems. PLE is a well-es ablished
echniqueandhasbeenused o heex ac iono awide
a ie y o compounds om nume ous ma ices [84–88].
To a lesse ex en , supe c i ical- luid ex ac ion (SFE) has
been used o he ex ac ion o EDCs om solid samples and
has been epo ed o exhibi se e al ad an ages (e.g., apid
ex ac ion, low sol en equi emen , low cos , and highe
e iciencies). SFE can be mainly applied o he ex ac ion o
nonpola and sligh ly pola analy es. Among all he sol en s
used in SFE, pu e CO2is hemos popula becauseo i slow
c i ical p ope ies, chemical ine ness, low oxici y and cos ,
and i s abili y o dissol e a wide ange o o ganic compounds,
including hose wi h high molecula masses. Ne e heless,
pu e CO2leads o low eco e ies o pola compounds. The
lack o ex ac ion e iciency o pola compounds can be
o e come h ough he addi ion o modi ie s o cosol en s
o hepu eCO
2, wi h wa e and me hanol being he mos
commonly used sol en modi ie s.
The p ope ies o supe c i ical luids a e in e media e
be ween hose o gases and liquids and depend on he
p essu e, empe a u e, and composi ion o he luids. Thei
iscosi y is lowe han ha o liquids, and hei di usion coe -
icien s a e highe , which leads o mo e e icien ex ac ions
[89]. A SFE sys em consis s o a high-p essu e pump ha
deli e s he luidandanex ac ioncellinwhich hesample
is main ained a he co ec p essu e and empe a u e. The
ex ac ed analy es a e apped in an o ganic sol en o on
a solid phase ( he analy es a e la e elu ed using an o ganic
sol en ). Pa ame e s such as he empe a u e, he p essu e,
he ex ac ion ime, and he collec ion sol en a e op imised.
The high a e o pene a ion o he supe c i ical luid in he
sample pe mi s he apid di usion o analy es, which educes
he ex ac ion ime. The comple e p ocess is pe o med in
less han 20 o 30 min ins ead o he se e al hou s equi ed
wi h o he echniques. An ad an age o SFE is ha he
ex ac s a e e y clean and equi e only mode a e addi ional
cleanup. Howe e , he small olume o he ex ac o , which
accommoda es only a ew g ams o ma e ial, is a disad an age
when a la ge sample mass is equi ed. The p inciples and
applica ions o his echnique o solid ma ixes and o
di e en ypes o compounds ha e been epo ed [90–93].
4. Endoc ine Dis up ing Compounds
The e is g owing ala m o e he po en ial ad e se e ec s
o en i onmen al con aminan s, such as hose in ol ing
he endoc ine unc ions. In his espec , we ocused ou
a en ion on some con aminan s o pa icula conce n ha
exhibi a ying deg ees o endoc ine-dis up ing p ope ies.
In pa icula , we concen a ed on ou ep esen a i e g oups
o compounds ha di e in hei na u e and o igin: na u al
and syn he ic ho mones, pe sonal-ca e p oduc s, alkylphenol
e hoxyla e and bisphenol A, and b omina ed lame e a -
dan s.
4.1. Ho mones. Ho mone esidues cons i u e a ecognised
g oup o eme ging en i onmen al con aminan s ha ha e
been p o en o a ec he biological ac i i y o o ganisms
exposed o hem. The ho mones in e e e wi h endoc ine
unc ion, and hei p esence in he en i onmen has been
obse ed o p oduce es ogenic e ec s, such as ish emini-
sa ion, changes in ep oduc ion and beha iou , a dec ease in
he amoun o spe ma ozoids, inc eased incidences o b eas
cance in women, and inc eases in ce ain anomalies in he
human ep oduc i e sys em, e en a low concen a ions [10,
16 BioMed Resea ch In e na ional
subsequen agmen a ion o p ecu so ions, which esul ed
in an enhanced p oduc -ion (EPI) expe imen .
Zhou e al. [131] s udied he use o liquid ch oma og a-
phy wi h a mosphe ic-p essu e chemical ionisa ion (APCI)
andem mass spec ome y (LC-APCI-MS2) o analysis o
38 HFRs om was ewa e samples and ound ng⋅L−1 le els.
Compa ed wi h APPI, APCI does no equi e a UV lamp
and a dopan eagen o assis he a mosphe ic-p essu e
ionisa ion.All heisome sand heisoba iccompoundswe e
well esol ed wi hin 14 minu es o LC sepa a ion ime.
Ueno e al. de eloped a me hod o de e mining he
occu ence o hyd oxyla ed PBDEs (OH-PBDEs) (me abo-
li es o PBDEs) in abio ic en i onmen s [167]. In his s udy,
OH-PBDEs we e de e mined in samples o su ace wa e
and p ecipi a ion ( ain and snow) collec ed om si es in
On a io, Canada. OH-PBDEs we e de ec ed in all he samples
analysed. The esul s in his s udy sugges ed ha OH-PBDEs
we e ubiqui ous in he abio ic en i onmen and we e mos
likely p oduced h ough eac ion o PBDEs wi h a mosphe ic
OH adicals. In addi ion, he au ho s specula ed ha hey
maybep esen insu acewa e nea STPsdue ooxida iono
PBDEs and in lows om me abolism by humans and animals.
Soxhle ex ac ion is a widely used s anda d echnique
o he de e mina ion o b omina ed lame e a dan s (BFRs)
in sewage sludge. Howe e , new ex ac ion echniques (e.g.,
USE, MAE, and PLE) ha e also been e alua ed.
Ruan e al. [168,169] epo ed, o he i s ime, he
disco e y o a new class o b omina ed lame e a dan ,
is (2,3-dib omop opyl) isocyanu a es, in he en i onmen .
These compounds we e ound in all o he i e wa e ,
sedimen , soil, and bio a samples analysed om a ac o y-
pollu ed a ea in sou he n China. The au ho s de eloped
a high-pe o mance liquid ch oma og aphy- andem mass
spec ome y (HPLC andem MS) me hod. Wa e sam-
ples we e ex ac ed using a SPE p ocess. Soils, su ace
sedimen s, ea hwo m, and issues/o gans o ca p samples
we e ex ac ed wi h dichlo ome hane (DCM) using accele -
a ed sol en ex ac o (ASE).
An LC-IT-MS me hod employing ESI ope a ed in neg-
a i e ionisa ion mode was de eloped o de e mine HBCD
dias e eoisome s in ma ine sedimen samples; he LOQs
anged om 25 o 40 pg⋅g−1 (dw). Ta ge analy es we e
ex ac ed om sedimen samples by MAE. The e iciency o
his echnique was compa ed wi h hose o Soxhle ex ac ion
andPLE,and heob ained esul sshowed ha MAEp o ides
be e ex ac ion e iciencies han ei he PLE o Soxhle
ex ac ion [134].
In ano he pape , he ex ac ion e iciency o p es-
su ised liquid ex ac ion (PLE), mic owa e-assis ed ex ac-
ion (MAE), and ul asonic-assis ed ex ac ion (UAE) unde
di e en condi ions was compa ed o he eco e y o he
mos commonly employed b omina ed lame e a dan s
(BFRs) om s y enic polyme ic ma ixes. A HPLC-MS2
me hod combined wi h PLE esul ed in comple e ex ac ion
o TBBPA and HBCD (95–100% eco e y) and in e media e
eco e y a es o deca-BDE (50%). The pe o mance o
MAE, howe e , was simila o ha o PLE o HBCD, bu
lowe ex ac ion yields we e achie ed o TBBPA and mainly
deca-BDE. Ul asonica ion, in compa ison, o e ed ela i ely
low ex ac ion eco e ies (10–50%) [170].
To ex ac PBDEs om biological samples, mul is age
liquid-liquid ex ac ion wi h sol en s o di e se pola i y is
used. The p elimina y p ocess includes dena u a ion o he
p o einsin hesamples.Themaindisad an ageo hisp ocess
is o en he long ime equi ed o each di ision o phases
o he necessi y o sample cen i uga ion. The amoun o
sol en s used can be educed h ough he applica ion o SPE
and ano he ex ac ion echnique.
G´
oma a e al. [138] epo edame hod o he
enan iome -speci ic de e mina ion o HBCDs by LC-ESI-
MS2 om ood samples. Food samples, wi h he excep ion
o bu e , which was ex ac ed by dialysis in n-hexane, we e
ex ac ed by ma ix solid-phase dispe sion (MSPD) wi h an
ace one : n-hexane mix u e (50 : 50, / ). The de ec ion limi s
anged om 1.5 o 4.3 ng⋅mL−1, and he epea abili y and
ep oducibili y, exp essed as he ela i e s anda d de ia ion,
we e less han 6% and 13%, espec i ely.
A comp ehensi e, sensi i e, and high- h oughpu liq-
uid ch oma og aphy-a mosphe ic-p essu e pho oionisa ion
andem mass spec ome y (LC-APPI-MS2)me hodwas
de eloped o he analysis o 36 halogena ed lame e a -
dan s (HFRs) om wen y- wo ish samples. Au oma ed
p essu ised liquid ex ac ion (PLE) was applied. Unde he
op imised condi ions, all o he HFRs we e elu ed om he
LC column wi hin 14 min. Excellen de ec ion limi s ha
a e aged 4.7 pg⋅g−1 we e ob ained [139].
Tang de eloped a me hod o he simul aneous de e mi-
na ion o h ee dias e eoisome s o hexab omocyclododec-
ane (HBCD) in human plasma using liquid ch oma og aphy-
andem mass spec ome y (LC-MS2). The simple p e ea -
men in ol ed p o ein p ecipi a ion wi h me hanol (MeOH).
The eco e ies anged om 79.0% o 108.9%, and he LOQ
was 10 pg⋅mL−1 o each dias e eoisome . No signi ican
ma ix e ec o ca yo e e ec o he analy es was obse ed
in his s udy [171].
Table 4 shows di e se de e mina ions o hese com-
pounds in biological and en i onmen al samples.
5. Conclusions and Fu u e T ends
Va ious ypeso na u alandsyn he icchemicalcompounds
ha mimic o inhibi he na u al ac ion o he endoc ine
sys em in animals and humans a e de ined as EDCs. The
ace concen a ion le els o EDCs and hei di e si y in
a ious aqua ic en i onmen s ha e been ecognised. One o
he ongoing esea ch ends conce ning EDCs in ol es he
iden i ica ion and de e mina ion o hei e ec s on bo h he
en i onmen and humans.
Fo he quan i a i e analysis o EDCs, mass-based ana-
ly ical me hods exhibi excellen sensi i i y and p ecision
o indi idual EDCs. The applica ion o ad anced LC-MS2
echnologies o en i onmen al and biological analyses has
expanded he ange o compounds ha can be analysed,
which has pe mi ed mo e comp ehensi e assessmen s o
en i onmen al con aminan s. In ecen yea s, ad anced

BioMed Resea ch In e na ional 17
ins umen s, such as LC-MS2, LC-TOF-MS, and LC-LIT-MS,
ha e been de eloped and widely employed in he analysis
o EDCs in en i onmen al and biological ma ices. These
ad anced ins umen s ha e been shown o be help ul in
he quan i ica ion o ace le els o hese compounds wi h
high p ecision and sensi i i y. In addi ion, hese analyses
p ocesses ypically equi e an ex ac ion s ep p io o he
ins umen al p ocedu e. The ex ac ion s ep plays a key ole
in de e mining he o e all le el o analy ical pe o mances,
and se e al echniques ha e been de eloped. Wi h espec
o he i s s eps o he analysis (i.e., he sample ex ac ion
and pu i ica ion s eps), an ex ensi e amoun o de elopmen
has been pe o med o ob ain g eene me hodologies, such
as SPE, SPME, and LPME o liquid samples and USE, MAE,
PLE o solid samples, ha consume less sol en and ene gy.
In addi ion, nume ous imp o emen s ha e been de i ed om
he de elopmen o new ma e ials o hese i s s eps o he
analysis.
Addi ional esea ch is clea ly needed o de e mine he
b eakdown pa hways and o e alua e he a e o he ans-
o ma ion p oduc s o EDCs. The e o e, he de elopmen
o u u e gene ic analy ical p o ocols should pe mi he
simul aneous de e mina ion o pa en compounds and hei
me aboli es.
Nume ous s udies ha e shown ha o ganic pollu an s
a e incomple ely elimina ed du ing was ewa e ea men
p ocesses; hus, he nex ask is o imp o e he ea -
men p ocesses o emo e a la ge numbe o e y di e en
mic opollu an s. The challenges include he iden i ica ion o
new eme ging compounds, he es ablishmen o app op ia e
s anda ds, he de elopmen o s a egies o educe inpu s
o he aqueous en i onmen , and he applica ion o no el
moni o ing me hods.
Acknowledgmen
This wo k was suppo ed by unds p o ided by he Spanish
Minis y o Science and Inno a ion, Resea ch P ojec no.
CTQ 2010-20554.
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