792
www.klinickafarmakologie.cz340804301076513320121425327329234035839843647950254457164568672477179183988990895196610061045
/26988043010732
Klin277580430107446583131
Farmakol2926804301074279105179220258305325
Farm3271804301074178105179
2023;37(3):86-883470804301074487128172186230270290333354368412457487532577
/40928043010731
KLINICKÁ4169804301074588109168189243289347
FARMAKOLOGIE4537804301074291138211266312372415475534555598
A51578043010752
FARMACIE5231804301074191138210265316337380
8756558026012657114
EDITORIAL5092207012655130163222297362395465520
The190636501063071103
importance202536501061569103144180212248289324356
of239736501063869
a2482365010637
fast-track253536501062967101133158186222264297333
pharmacology288336501063374114149204245278317348387427465
for336336501062970106
the348536501063071102
proper360336501063368109144176211
management383036501065293134174211243298330371403
of424936501063869
antibiotic433436501063879111129165183223254272306
therapy465636501063071103139180215252
in492436501061556
intensive49963650106155688120162194211249281
care529336501063274109142
units54503650106398098130162
usually343286101094985135179201223267
coupled627286101094190140192215261314
with958286101096688119170
ultraviolet1145286101095072102133177220242293315362393
(UV),1555286101092684135164182
photo-17552861010951102152183232264
-dyode343300101092882126176229275
array637300101094373104149192
(PDA)847300101092674134188214
or1079300101095081
fluorescence1178300101092651102153183230266308354405447492
detector1688300101095198129175217250300331
(Table343314101092674113165188235
2).60231410109467189
This715314101094496118154
approach893314101094496149180230275317368
further1285314101092677108142192239270
evolved1579314101094589139162207252305
towards19083141010930803433281010965109139189224
immunoassay584328101092196170220269319363398434478519
analysis1120328101094393136158200236257293
to1429328101093078
accommodate1524328101094384123171246321371422466343342101092973
minimal433342101097495144165240283304
sample754342101093579153204226271
preparation1041342101095181125176220249293322343393443
and1500342101094392143
faster1660342101092569105135179209
turnaround1886342101092978108343356101095094125175226277330
times.697356101092951128174211232
However,9533561010958110177222267312343359
the1336356101093080127
immunoassay1487356101092197174224275326371408444489532
technique343370101093077120172224246299351398
is769370101092259
only8563701010950102125170
available1054370101094488134157179225278302349
for1431370101092779110
a15693701010944
restricted1641370101093077115147178201244278324378
range343384101093076128182229
of601384101095078
antibiotics.708384101094496128150204227279311334376415437
Recently,1173384101094997141187240271294339356
commercial1557384101094192171248297328371393439462
kits34339810109426595132
for492398101092676106
the615398101092979125
quantification7573981010950100144194223245272296336381410432482532
of1306398101094976
antibiotics1399398101094393122144195217267297318359396
using1812398101094985106156207
LC343412101094293
coupled453412101094089139190213259311
with781412101096688118168
mass9664121010975119154190
spectrometry1174412101093586133174207237286362408439469514
(MS/MS)1706412101092596140171243288313
have343426101095197141188
been5604261010952101149202
developed791426101095199145192215268322371425
(11).1245426101092670110131150
These14234261010946100148186234
kits1685426101094368100139
may18524261010977123167
overcome343440101094993139169211260337383
previous747440101095182128173195246297333
limitations1101440101092143119142173218248270321373409
on15304401010950101
the1652440101093081127
widespread1800440101096689141188343454101093587118163207259
use620454101094985131
of769454101094976
LC-MS/MS862454101094393117191236267339384
methods12644541010974121152202253305341
in1622454101092172
hospital17114541010950100137188210241286308
laboratories,343468101092166118170201246276326357379426463483
such845468101093686128179
as1043468101094380
the1142468101093080127
need1288468101095097144197
for1504468101092677108
dedicated1631468101095197150172214259289335388
personnel343482101095198129167218269320367390
with754482101096688120170
expertise945482101094589142189220254276312359
in1324482101092273
the1417482101093081128
field.156648210109265197120172192
Therapeutic3435070014763133195239300371434503545576630
drug10015070014769113181251
monitoring127950700147102170240270313380424455524593
to3435210014742110
limit480521001473162164195237
antibiotic7445210014761130172203273305373416446501
toxicity12725210014742110168200254285327390
The483538101094494139
TDM6375381010944104175
of828538101094874
antimicrobial917538101094392121141215236276304353403424467488
agents1420538101094392137187215251
has1687538101094991126
been1828538101095196141191
clearly343552101094062107151181202245
proven614552101095181131173218269
to908552101093079
be1012552101095198
of1135552101095076
clinical123755210109406182132153194238260
relevance152255210109297597142186230280321365
for1913552101092676106
the343566101093080126
management4865661010975119169212263309384430481510
and1014566101094393144
prevention1176566101095181126169214264294315365415
of1609566101094976
drug-related170256610109518013018121024128634358010109216595141193
toxicity.562580101093079121143184205236282297
Indeed,885580101092272124170217269289
extensive1200580101094588121167218253275319364
evidence1590580101094589111163209260301346
is1962580101092157
available343594101094486131152174218270292338
demonstrating707594101095197174224275311342372417447468519570
that1303594101093080124154
aminoglycoside-associated14835941010944120141192242294316360400449485506343608101095197128172208244295336358402432477529
nephrotoxicity898608101095197149200230280310360402424465486517562
or1486608101095080
ototoxicity,1592608101095080130160209251273314336366412427
vancomycin-associated343622101094488138179228305346386408458488532567603654695717760790835887
nephrotoxicity,1256622101095096148200229279309359400422463484514560575
colistin-related185762210109408911113334363610109366788138168199244267310340385438
nephrotoxicity806636101095096148199229279309358400422463484514560
and1391636101094494146
teicoplanin-156363610109297496137186238260304355376426456
-associated343650101092873109146197240261306336382435
neutropenia805650101095197149180210261314362413435480
are1311650101094475121
dependent1458650101095299152199251303350402432
on19176501010950102
the343664101093183131
absolute502664101094598136188212263295342
drug872664101095384136189
concentrations1090664101094192145188234287318349395426449501554591
and1709664101094597151
the1888664101093183131
duration3436781010952103133179209231283335
of704678101095178
exposure.809678101094690143195232283314360380
This1215678101094698120157
provides1398678101095284134179201254301338
a17636781010944
solid1833678101093788111133186
rationale343692101093075105127178230274296343
for712692101092778109
the847692101093082128
adoption1002692101094496147200231253304356
of1384692101095077
trough-based1488692101093060111162214265296349395431478531
TDM3437061010945106179
as547706101094479
mandatory6527061010975118169220264293342373418
tool1096706101093079129151
to1273706101093079
optimize13777061010950101132153228249288334
the1736706101093080126
use1887706101095086132
of343720101094976
these438720101093080126161207
antibiotics664720101094494123144196217267297318359396
in1079720101092171
clinical116972010109406283133154194239260
practice1448720101095181125166198219260304
(12).1771720101092668108132149
Beta-lactam483734101094997129175206230276318352398475
antibiotics981734101094395127150203226278310332375413
are1417734101094475122
usually1562734101094987138183206229274
well18597341010966113137160
tolerated.343748101093080104151183228260306359380
Drug-related743748101095991143196226259305329374405452505
toxicity1268748101092980123146188211243289
is1577748101092158
generally1654748101095098150197229274297320365
ascribed343762101094482125157181235284338
to711762101093081
hypersensitivity822762101095194149198230270318371408432464488534558590638
reactions,1490762101092977123166201224277330367389
regardless1909762101092977343776101095094124176198244281317
of679776101094976
drug774776101095080131182
dose9757761010950100137183
or1177776101094879
drug1275776101095080131182
overexposure.1476776101094892137168214257310361397447478523543
However,21384681010959111179225270317348365
a25284681010943
retrospective2596468101093077109141192229282330374408431476523
analysis3144468101094395140163208246269306
by3475468101095195
Imani3595468101092199144196219
et2138482101094577
al.224448210109446788
documented23614821010951103146197274322374406452506
significant2896482101093658111163186215240283329381412
associations3337482101094381118170213236281313336387440477
between21384961010953103137210259309363
toxic2532496101093184129153198
concentrations2761496101094194148193241295328361409442466520574613
of3405496101095181
piperacillin,3517496101095377133183216264213851010109416588112136189210
meropenem,23785101010976125158210265314368417496517
flucloxacillin2925510101092753106150173226270317361384408432455508
and3463510101094497152
drug-related36455101010951841372138524101095183117166190237270317373
neurotoxic/nephrotoxic25415241010951100154186239272324368393437473524573628682715768801853897922965
effects3537524101094676108157202237277
(13).2138538101092672117143163
Similarly,2335538101094670150174199247280305352370
consistent2738538101094295149188213252286335389422
and3194538101094599154
significant3382538101093761116170194225252296345399432
associations2138552101094381118170213236281313335387439476
have2643552101095096140186
been28585521010951100148200
reported3087552101092976130182214249295349
between3465552101095199131202249297349
high2138566101095073126179
cefepime2346566101094087116164218241319367
trough2742566101093062114166219271
concentrations3043566101094091144187233286317349395427450502555592
and3665566101094395149
drug-related2138580101095182134187218250297321366398444498
toxicity2659580101093080123147189212244291
(14).2973580101092569112138157
The2278594101094597143
oxazolidinone2447594101095092136176226249270322344394445496543
antibiotic3015594101094495125146198220271301323364
linezolid340559410109214394140180230252274326
is3757594101092157
associated2138608101094379114165206227270300345397
with2551608101096688118168
severe2736608101093581124169199244
adverse2996608101094495139184213250296
effects,3308608101094573102148189221258278
including36026081010921711121331832138622101095274125177
thrombocytopenia,2341622101093182112163240293345387433467518571618670692736756
peripheral3124622101095299130152205257304335380402
neuropathy,35526221010951981491802302138636101095297127177219235
lactic2399636101092165107139161202
acidosis2627636101094485106158209245267303
and2955636101094495147
optic31286361010950103133155196
neuropathy.3350636101095097147178228280325355406448464
Without2138650101097699129179230280310
accurate2474650101094485124174204249278323
management,28236501010975119170214265311387433484513533
the3382650101092980126
toxicity3533650101093080121143184205235281
of2138664101095179
linezolid224666410109224597145186238261284337
may26126641010978123167
outweigh28086641010951103135207254277330382
the3219664101093183131
benefits33796641010953102154202231256288327
of3735664101095179
continuing2138678101094190141172193244294316367418
treatment2582678101093061107151181257304355385
for2993678101092777108
extended3127678101094689122168219271317370
periods3523678101095299129151202255291
of2138692101094976
time,2237692101093051127172191
as2451692101094479
the2554692101092979125
risk270369210109295186128
of2855692101094976
adverse2954692101094395139183213250296
effects3273692101094572102147189221258
increases35546921010921721121421872312138706101093681117
with2271706101096788118168
exposure2456706101094587139190226275305350
and2822706101094393145
duration29837061010950100130174203224274325
of3324706101094976
treatment.3416706101093059104148178253299349378398
Monitoring21387201010972123173194224273303325375426
trough2585720101093060109159210260
concentrations2867720101094089139180225275305334378408429479529565
is3453720101092156
used3531720101094985131183
to3735720101093079
prevent2138734101095180125167211260289
linezolid244373410109214191136174223244265315
toxicity.2774734101092977118139179199229273288
Decreasing30777341010960105146175219262297318367417
the3509734101093079124
linezolid3648734101092142911362138748101093988110131182
dose23397481010951101137182
and/or2540748101094393145177223253
frequency,2811748101092757102154204250300341386401
whenever32307481010967117163214259302347377
trough362674810109305910915921387621010950101
concentrations2264762101094089140181225276305335379409430480530566
exceed2855762101094588128172219271
a31517621010944
pre-established3220762101095181127157205241272316367390411446496542594
toxicity2138776101093079120142182203233279
threshold2438776101092979109154190240290312363
(usually2822776101092673108158201223244287
set3130776101093681112
at3263776101094373
833577761010946
mg/L),34157761010975126158201226243
can3679776101094185135
decrease3934468101095196138167213256292338
the4290468101093080126
risk443546810109295186128
of4582468101095076
toxicity,4677468101093079120142182203234279294
primarily4990468101095181102178221251272294337
thrombocytopenia534646810109307910915823439344821010951102143188221270322368419440483
(15).4436482101092668109133150
Matching39345070014799159199250316345411478
fast-track4435507001473897145186217257297356408467
microbiology492450700147102131183223289358387452482548615674
with39345210014790119159226
fast-track4182521001473898145186218257297356408467
pharmacology:46725210014770137196236336396447512541607675734761
new39345350014769129216
timings4173535001474270170198265332380
of45765350014767104
PK/PD47025350014767134177242321
assessments39345490014761109156217265312412472539579628
at45845490014761101
the47075490014743109169
bedside48995490014770131200248276344404
The40745661010946100149
significant4254566101093660114167190219246289336389421
variations4706566101094592124147194226249302356394
in5130566101092275
the5236566101093184132
PK53995661010949100
of5530566101095180
antibiotics3934580101094495126148201224276307329371409
in4371580101092173
critically447258010109407194125148190235258280325
ill482558010109214366
patients4918580101095298129151198250281319
and5265580101094395148
how54405801010951102170
the3934594101093081127
TDM40825941010945107180
can4283594101094186137
help4440594101095097120172
to4633594101093080
quantify47335941010951102146197228250277324
the5078594101093081127
individual5226594101092172125147191214266317361384
variations3934608101094286115136179209229279328363
have4313608101094992134178
been4507608101095096141191
reported4714608101092974125175204237281332
in5062608101092070
the5148608101092978124
previous5288608101095080124167188237287322
sections.3934622101093682125158180230282318339
Nevertheless,42956221010959106150195226260311357380427464500520
the4838622101092980127
PK4987622101094897
of5106622101095077
antibiotics5205622101094495125147199222273303325367405
may39346361010974117159
have4110636101094992134179
limited4306636101092142116138168212264
clinical458763610109406182132153194238259
consequences4863636101094088138174219271320366416456501537
if5416636101092148
not5481636101094999129
adequately3934650101094498147201253300331379402448
matched44116501010976123154196249297352
with4792650101096791123176
their4997650101093083131155186
PD,52126501010949111129
which53706501010968121144187240
reflects3934664101093076104129176219252290
the4251664101093082128
relationship440766410109297699144174196248299336387409462
between4896664101095199131201247294346
the5269664101093081128
drug5425664101095181133185
concentrations3934678101094090141183228280310340385416438488540576
and4528678101094394146
the4692678101093081128
antimicrobial4838678101094394124146222244286316367419442486508
effect.5364678101094573104150192225246
The3934692101094597143
primary4097692101095182104180225255302
measure44186921010975122166203253284330
of4767692101094977
antibiotic4863692101094394125147199222272303325367
activity5249692101094385118140184207238284
is5552692101092258
the3934706101093080126
minimum4078706101097496147168244294370
inhibitory4465706101092172122144196218248298328374
concentration4857706101094089140181226277307337382412434484535
(MIC)5410706101092596119172200
that3934720101093081125156
prevents4113720101095182128172218269300337
the4474720101093080127
pathogen4625720101095196126177228280327378
growth5027720101095081131198232283
in5333720101092170
vitro.54237201010941629112116855917201010919
When39347341010976128175226
the4181734101093081127
MIC4329734101097396150
is4500734101092157
not45787341010950101132
available,4731734101094487132154176220273296342361
international5114734101092172102148178230274305327378429474496
breakpoints3934748101095284131176220275328351403434472
can4434748101094187139
be46017481010952100
used4730748101095087135188
as4947748101094481
surrogates5056748101093687118150202255300332378416
for5500748101092678110
the3934762101093081128
actual4090762101094385118169214237
MIC.4354762101097396150172
However,45547621010959110178224268314345361
it4943762101092152
is5022762101092258
important5108762101092197150202233267312364394
to5530762101093080
highlight3934776101095072124175197219271322352
that4310776101093080125155
the4489776101093081127
MIC4640776101097396150
value4813776101094489111161208
simply5045776101093557133186209253
reflects5321776101093076104129175218251289
Tab.34061701124993148172
1.53261701125071
Factors65062201073984122151195222254
that92262201072773119146
could108662201073882128148194
potentially129862201074592118156203229248294313332370
alter16866220107456591129156
the186062201072673112
pharmacokinetics199062201074592138165237283322366404424471510537556594627
and263562201074592138
clinical27916220107385776123142180225244
response30536220107266496141188235266304
of337562201074569
antibiotics346262201074592118137183203249276295333365
in384562201071966
intensive39296220107186591129176207224263301
care424862201073883109147
unit441362201074593111138
patients456962201074592119138177224250282
Changes3717590984793134181228270304
Effect1549759098416896138175206
on17717590984592
drug18807590984675122169
pharmacokinetics20657590984794135164233274311356398420467509538559596631
Impaired3718820951783127164181205243288
drug6778820954367110155
absorption8498820953781111155179224249266309352
Reduced15498820954080125167204242287
bioavailability18538820954462105142178215232249285330347364381406445
of23158820954364
orally23978820954267104121138174
administered25898820953680146163206223252278316340379424
antibiotics30308820953679104121165182226250267303335
(not33828820952162106130
frequent3530882095214684129172211254279
in38268820951760
critically3903882095366077103120156193210227263
ill4184882095163350
patients)42528820954481106123162205230261280
Hypoalbuminemia37110020955086132176213230274318383400443483549566602
Increased15491002095176096120159195225264309
drug187610020954367110155
clearance20481002095365392128152190233269307
and237310020953679123
higher251410020954360104147186210
risk27421002095234170104
to288110020952567
fail2965100209521597693
PK/PD307510020954080112154205
target32971002095256286129168194
attainment35081002095366188125142185251291334358
(most388310020952285129159185
relevant40861002095236279119155192236260
for43631002095216488
renally446910020952362105142159176212
excreted469810020953975110134172197236280
antibiotics499610020953679104121165182225250267303335
with534810020955875101144
protein154911020954468111135173190233
binding180011020954461104149166208253
>2070110209548
80%)212811020953979139159
Obesity37112220955499139169186211249
Changes154912220954688125168212252282
in184912220951659
the192612220952468107
Vd,20511222095418297
hepatic216512220954383127164189206242
drug242512220954367110155
metabolism2597122209566105130168212256274291320385
and300012220953679124
renal314112220952462105142159
excretion331812220953974110133172197214257301
for36361222095216488
hydrophilic374212220954377121145187232275292309326362
antibiotics412112220953780104121166183226251268304335
(i.44741222095213852
e.453612220953952
beta-lactams,460612220954484109147172190227263290327393423437
vancomycin)506112220953673116153195261295331348391410
Renal37113420954080123160177
insufficiency5651342095176090132154178196232249289332368406
Reduced154913420954080125167204242287
clearance18531342095365392129152190233269307
of217813420954264
hydrophilic226013420954277121144187231275292309326362
drugs263913420954468111155185
with284113420955875101144
increased30031342095165996119158194224264308
risk33291342095244171104
to346813420952567
reach35521342095246399135178
supra-therapeutic374813420952972116140178203228271311335372417457500525542578
plasma43441342095446298128194230
concentrations459213420953577121157195238263287324349366409452482
and509213420953679123
to523313420952466
develop531713420954383119158176219264
drug-related154914420954467111155180205243261297322360405
toxicity197114420952567101118155171197235
(i.e.2223144209522385392106
beta-lactams,234614420954485110147172191227263291328393423438
aminoglycosides;2801144209537102119162206250268303339381411428472511541555
glycopeptides)33731442095446197133174219260304329346390430460479
Hepatic37115620955090135172196213250
insufficiency6381562095176089132153178196232249288331368406
Increased15491562095176096120159195225264309
risk18761562095234170104
of199815620954264
accumulation207915620953773108151216259276313337354397441
of253715620954365
antibiotics261915620953680104121165183226250267303335
with297115620955875101144
high313315620954259103146
hepatic329715620954382127164189206242
extraction355615620953975102126164200227245288331
rate.39051562095236185123137
For405915620953780104
the418015620952568108
remaining,430515620952463128165182225242285329343
the466615620952468107
effects47911562095396085124161188219
on502815620954286
drug513115620954468111155
pharmacokinetics154916620954488124148215251288329364382425465490507543575
are21411662095366099
less22571662095175787117
predictable239116620954569107152169205233270314332371
Augmented37117820954789133199238282306344389
renal77717820952462106142159
clearance9541782095365392128152189232269307
(acute3711882095215692135160198
hyperdynamic58718820954377123163187230266310347413429466
phase)107018820954488125154194214
Increased15491782095176096120159195225264309
clearance18761782095355392128152189232269307
of220017820954365
hydrophilic228217820954378121145187232276292309326362
antibiotics266217820953679103121165182225250267303334
with301417820955875100144
increased31751782095176096120159195225264309
risk35021782095234170104
of364117820954364
sub-therapeutic372317820953072116143168211251275312356397439465482518
plasma42591782095446298128193230
concentrations450717820953577121157195238262287324348365409452482
(i.e.1549188209521385292105
beta-lactams,167218820954484109146172190227263290327393423437
linezolid)21271882095173476116149192209226270292
Altered3712002095476489128151190235
fluid6232002095214284101145
balance7852002095458299136179215253
(increased10562002095213880117141179215245285330
capillary37121020953673117135152169205229267
permeability)65621020954484108175214250295312329346371409430
Expansion154920020953774119156199229246289332
of189920020954264
extracellular198120020953874101126163199237255272314331368392
fluid23902002095214184101145
volume25522002095377997139205245
leading28142002095175793137154197241
to307320020952466
increased31572002095165996120158194224264309
drug348320020954467111155
Vd365620020954082
and375620020953679123
lower389720020951760118157181
plasma40952002095446299129194231
drug434320020954468111155
concentrations.451620020953577121157195238263287324349366409452482497
This15492102095378299128
effect16952102095386084123160188
is190021020951746
particularly196421020954481105133150186229246283306324360
relevant23422102095236279119155192235260
for26372102095216388
hydrophilic274221020954378121145187232276293310326362
antibiotics312221020953679104121165182225250267303335
with347421020955875101144
low363521020951761118
Vd377121020954183
(i.38712102095213852
e.393321020953953
aminoglycosides,4003210209537102119162205250267303339381411427472511541556
beta-lactams)457621020954585110147172191227263291328394423442
Extracorporeal37122220953774102126163199241266311355379418454471
clearance8592222095365393129152190233269307
for11842222095216388
organ128922220954367110147190
support37123220953072116161205230257
(RRT,64623220952162103141151
ECMO)81523220953783145200220
increased15492222095176096120158194224264309
Vd187522220954183
and197522220953780124
clearance21172222095355292128152189232269307
of244122220954364
hydrophilic252322220954377121145187232275292309326362
antimicrobials290322220953679103120186203239263305350367404421450
with337122220955775100143
increased35322222095176096120158194224264309
risk38582222095244171105
of398022220954364
drug406222220954367111155
underexposure423422220954386130170194232268313357387429453491
PK-driven37124420954079101147171189225264307
drug-drug69624420954367111155180226250293337
interactions10512442095165984122146183219247264307350380
Increased15492442095176096120159195225264309
risk18762442095234170104
of199824420954264
suboptimal207924420953072117161206230248313350367
exposure246324420953975120164194236260298
of277924420954264
antibiotics286124420953679103120165182225250267303334
when3213244209558101141184
co-administered341424420953678104141185251268311327357383421445484528
with396024420955875100144
drugs412124420954468111155185
affecting43232442095375882121158186203246290
the463024420952568108
ADME475624420954698161199
phases497224420954488124154194224
Vd:3712562095407790
volume4762562095337390131194229
of71925620954061
distribution;7942562095405784107130147187228251268308350363
RRT:117125620953978113122
renal13072562095235698138155
replacement14762562095235697114155188221285319361383
therapy;18742562095236499122160201233248
ECMO:213625620953578139191205
extra23552562095346994117155
corporeal25252562095337295136177200233274291
membrane283025620956498162202225264305340
oxygenation;318425620954072108148182224264287304344386399
ADME:359725620954393154189203
absoption,381525620954080108147188212228268310324
distribution,41542562095405783107130146187228251267308350364
metabolism,453225620956498122161201242259276302365379
elimination.49262562095335067130147188228252268308350365
Tab.2140284501124993148172
2.2332284501125076
Available2455285001074886130150169215261280319
analytical2792285001074693139158196225244282327347
techniques3157285001072663102149196214261307346378
for355328500107236895
the3666285001072673112
TDM3796285001074098166
of3980285001074569
antibiotics4067285001074593119137183203249276295333366
Separation217131400953777121159182220244261304348
techniques253631400952563100143186203247290329360
„3325301106745
Gas340529900955087117
chromatography353929900953679103145211248272314359383420464508543
(GC)409929900952170116139
„3325311106745
High340530900955067111154
performance357730900954484108132175199266302345382420
liquid40143090095173478121138182
chromatography421330900953679103145211248272314359383420464508543
(HPLC,477330900952172112147191205
LC)499630900953679102
„3325321106745
Ultra-high34053190095506792116154179223240284327
performance375031900954484108132175199265302345382420
liquid41873190095173478120137181
chromatography438631900953679102145211247272314358382420464508542
(UPLC/UHPLC)494631900952171111146190221272322363398441464
„3325331106745
Capillary340532900954683127145162178215239277
electrophoresis37003290095395695132160184226271315358382421451468497
(CE)421532900952165102125
Identification/quantification217135100951761101144168185207225261298323340383426456496539575618642659681699735772797814857901
techniques217136100952563100143186203247289329359
„3325343106745
Mass340534100956299129159
spectrometry358234100952973114151178202244311350375399438
(MS)403834100952182119140
„3325353106745
Mass340535100956299129159
spectrometry,358235100952973114151178202244311350375399438449
single40483510095304790134151190
quadrupole425635100954386122167191234278322340380
(SIM,46533510095215773136151
SRM,482135100953877140155
MS)499435100956299121
„3325363106745
Mass340536100956299129159
spectrometry,358236100952973114151178202244311350375399438449
multiple4048361009566108126151168212230269
quadrupoles433536100954386123167191234278322340380410
(MS/MS)476336100952182119147210247268
„3325373106745
High340537100955067111154
resolution35773710095236292136154196221239282325
mass3920371009565102132162
spektrometry409937100953074114149176201243309349374398436
(HRMS)455337100952172112175213234
Combined217140300954687154198216258298343
technologies253140300952563100143186230248291336353392422
„3325385106745
LC-MS/MS34053830095367994158195224286323
„3325395106745
GC-MS/MS340539300955096111175212240303340
„3325405106745
LC-HR-MS/MS34054030095367994146187212276313341403441
„3325415106745
CE-MS/MS340541300954683107170208236298336
„3325425106745
CE-HR-MS/MS340542300954683107159199224288325354416453
Immunoassays217143500951783148191234277315345375412447478
(FPIA,26664350095215898114160176
MELA,2860435009562100135184200
EIA,307843500953753100116
etc)32114350095396499120