abu therapeutic drug monitoring by hplc · by hplc (reversed phase) improved online application now...

T H E R A P E U T I C D R U G M O N I T O R I N G / T O X I C O L O G Y

Therapeutic Drug Monitoring System by HPLC

For further information, please contact the Bio-Rad office nearest you or visit our website at www.bio-rad.com/diagnostics

© 2010 Bio-Rad Laboratories, Inc. Printed in Germany 8/10 EU-TDM-08/10E

Clinical Diagnostics Group

Website www.bio-rad.com/diagnostics U.S. 1-800-2BIO-RAD Australia 61-2-9914-2800 Austria 43-1-877-8901 Belgium 32-9-385-5511 Brazil 5521-3237-9400 Canada 1-514-334-4372 China 86-21-64260808 Czech Republic 420-241-430-532 Denmark +45-4452-1000 Finland 358-9-804-22-00 France 33-1-47-95-60-00 Germany +49-(0)89-318-840 Greece 30-210-7774396 Hong Kong 852-2789-3300 Hungary +36-1-459-6100 India 1-800-180-1224 Israel 972-3-9636050 Italy +39- 02-216091 Japan 81-3-6361-7070 Korea 82-2-3473-4460 Mexico +52 (55) 5488-7670 The Netherlands +31-318-540666 New Zealand 64-9-415-2280 Norway 47-23-38-41-30 Poland 48-22-3319999 Portugal 351-21-472-7700 Russia 7-495-721-14-04 Singapore 65-6415-3170 South Africa 27-11-442-85-08 Spain 34-91-590-5200 Sweden 46-8-555-127-00 Switzerland 41-61-717-95-55 Thailand 662-651-8311 United Kingdom +44-(0)20-8328-2000

Bio-Rad Laboratories T H E R A P E U T I C D R U G M O N I T O R I N G / T O X I C O L O G Y

Online Sample Preparation & AnalysisBio-Rad now offers the online column switching method with all three therapeutic drug monitoring kits, allowing for time-saving and convenient measurements of over 50 prescribed drugs and/or active metabolites.

Bio-Rad has developed a column switching method

that allows for direct online sample preparation and

analysis of serum and plasma samples. This involves:

• Enrichmentoftheanalytesonthereversedphase

extraction cartridge

• Eliminationofremainingmatrixand/orhydrophilic

components

• Transferoftheanalytestothereversedphase

analytical column

• Separationanddetectionoftheanalytes

Sample Clean Up

Sample Elution and Analysis

Test Procedure Diagram

Direct online sample preparation and analysis of serum and plasma samples by column switching.

HPLC Specifications

BZO/TCA RAPsyD Anti-Epileptic

2 Pumps 0.6mL/min or 1.1mL/min

low-pulsation flow rate. Pressure

rating up to 250kg/cm2

0.8mL/min low-pulsation flow

rate. Pressure rating up to

250kg/cm2

0.8mL/min low-pulsation flow

rate. Pressure rating up to

250kg/cm2

Pulse dampener Able to produce noise-free

baseline with a UV detector

sensitivity of 0.005 Extinction

units

Able to produce noise-free



units

Able to produce noise-free



units

Degasser Recommended Recommended Recommended

Injector Precise injection of 100ul

(Automatic sample injector)

Precise injection of 100ul


Precise injection of 50ul


Column heater Ability to maintain a constant

temperature of 45°C or 55°C

+/- 1°C

Ability to maintain a constant

temperature of 45°C +/- 1°C

Ability to maintain a constant

temperature of 35°C +/- 1°C

6-Way column switch valve Required Required Required

UV detector 233nm & 250nm; Sensitivity of

0.005 Extinction units (AUFS)

254nm & 278nm; Sensitivity of

0.005 Extinction units (AUFS)

210nm; Sensitivity of 0.02

Extinction units (AUFS)

Integrator Capable of recording &

analyzing output signal of UV

detector

Capable of recording &


detector

Capable of recording &


detector

pump pump

2autosampler

waste

switching valveposition 1

extraction cartridgeanalytical column

detector waste

1

pump pump

2autosampler

waste

switching valveposition 2

analytical columndetector wasteextraction cartridge

1

Antiepileptics by HPLC (Reversed Phase)

Manual Method and Automated Online Method Available

This assay is suitable for reliable, fast and easy quantitative determination of a

broad range of first and second generation antiepileptic drugs in plasma and

serum.Thepanelconsistsof11antiepilepticsand/ortheiractivemetabolites.

• Principle:IsocraticHPLCmethod(ReversedPhase)

• Durationofthechromatography:16.5min

• Samplevolume:100mLserumorplasma(manual),

40mLserumorplasma(onlinemethod)

• Flowrate:0.8mL/min.

• UVDetection:210nm

Test characteristics:

0.0

2.5

5.0

7.5

10.0

12.5

15.0

-0.0

130.

000

0.01

30.

025

0.03

80.

050

0.06

30.

075

0.08

70.

100

Time (min.)

AB

U

Sul

tiam

e

Zon

isam

ide

10-O

H-C

arb

azep

ine

Des

met

hylm

eths

uxim

ide

Lam

otrig

ine

Inte

rnal

Sta

ndar

d

0.0

2.5

5.0

7.5

10.0

12.5

15.0

-0.0

130.

000

0.01

30.

025

0.03

80.

050

Time (min.)

AB

U

Eth

osux

imid

e P

rimid

one

Car

bam

azep

ine-

Ep

oxid

e

Inte

rnal

Sta

ndar

d

Phe

nyto

in

Car

bam

azep

ine

Phe

nob

arb

ital

0.06

30.

075

0.08

70.

100

Chromatogram of the Antiepileptics Calibrator A• 10-OH-Carbazepine • Desmethylmethsuximide • Lamotrigine • Sultiame• Zonisamide

Chromatogram of the Antiepileptics Calibrator B• Carbamazepine • Carbamazepine-Epoxide • Ethosuximide • Phenobarbital • Phenytoin • Primidone

Therapeutic Drug Monitoring by HPLC• Benzodiazepines and Tricyclic Antidepressants • Psychoactive Drugs • Antiepileptic Drugs

Bio-Rad Laboratories T H E R A P E U T I C D R U G M O N I T O R I N G / T O X I C O L O G Y

Fast• Onlineapplicationavailableforhighspecimen

throughput

• Abilitytomeasuremultipledrugsand/ortheir

active metabolites with one kit

Easy• Reducedhands-ontimewithonlinesample

preparation

• Flexibleworkflowwithovernightprocessing

option

Reliable• Precisedatafortherapycontrol

• Efficienttherapeuticdrugmonitoring

TherapeuticDrugMonitoring KitsTherapeuticdrugmonitoring(TDM)isanacceptedtoolfor

optimizing treatment with medication such as antidepressants,

antipsychotics and antiepileptics.

Bio-RadLaboratoriesofferstheconvenienceofready-to-use

kits for therapeutic drug monitoring. These high performance

liquidchromatography(HPLC)kitscoupleconveniencewith

specificity, sensitivity and reliability for routine operation in the

clinical laboratory.

Withoneinstrument,2analyticalcolumns,and3panelsof

calibratorsandcontrols,morethan50drugsand/oractive

metabolites can be analyzed. Bio-Rad offers the following

HPLCkits:

• BenzodiazepinesandTricyclicAntidepressants

• RAPsyD(RapidAnalysisofPsychoactiveDrugs)

• Antiepileptics

Benzodiazepines and Tricyclic Antidepressants by HPLC (Reversed Phase)Improved online application now easily compatible with Bio-Rad’s RAPsyD by HPLC assay due to use of the same

analytical column, extraction cartridge and mobile phases

The Benzodiazepines and Tricyclics Reagent Kit provides a

reliable,fastandeasy-to-usemethodfortheanalysisof22

antidepressants, benzodiazepines, selective serotonin re-uptake

inhibitors(SSRIs),andtheirpharmacologicallyactivemetabolites.

The analytes are both extracted and separated online through the

column switching method.

Test characteristics:• Principle:IsocraticHPLCmethod(ReversedPhase)

• Durationofthechromatography:35min.(AnalytepanelA)/25

min.(AnalytepanelB,C&D)

• Samplevolume:600mLserumorplasma

• Flowrate:0.6mL/min(AnalytepanelA)/1.1mL/min(Analyte

PanelB,C,&D)

• UVDetection:250nm(AnalytepanelA&C)/233nm(Analyte

panelB&D)

min5 10 15 20 25 30

mAU

-2

-1

0

1

2

3

4

5

6

7

Nor

doxe

pine

Des

ipra

min

eN

ortr

ipty

line

Nor

trim

ipra

min

eN

orcl

omip

ram

ine

Dox

epin

e

Imip

ram

ine

Am

itrip

tylin

e

Clo

mip

ram

ine

Trim

ipra

min

e

Inte

rnal

Sta

ndar

d 1

min5 10 15 20

mAU

0

1

2

3

4

5

Flun

itraz

epam

Inte

rnal

Sta

ndar

d 2

Clo

naze

pam

min5 10 15 20

mAU

-5

0

5

10

15

20

Bro

maz

epam

Lora

zep

am

Tem

azep

am

Inte

rnal

Sta

ndar

d 2

min5 10 15 20

mAU

-5

0

5

10

15

20

Inte

rnal

Sta

ndar

d 2

Oxa

zep

am

Chl

ord

iaze

pox

ide

Alp

razo

lam

Des

alky

lflur

azep

am Nor

dia

zep

am

Traz

odon

e

Dia

zep

am

Tricyclic Antidepressants (Analyte panel A)

Benzodiazepines (Analyte panel B)

Coming soon

Selective Serotonin Re-uptake Inhibitors (SSRIs) (Analyte panel B)

Benzodiazepines (Analyte panel C)

Benzodiazepines (Analyte panel D)

• amitriptyline

• clomipramine

• desipramine

• doxepin

• imipramine

• norclomipramine

• nordoxepin

• nortriptyline

• nortrimipramine

• trimipramine

• alprazolam

• chlordiazepoxide

• desalkylflurazepam

• diazepam

• nordiazepam

• oxazepam

• bupropion

• citalopram

• escitalopram

• duloxetine

• fluoxetine

• fluvoxamine

• mirtazapine

• norfluoxetine

• paroxetine

• sertraline

• venlafaxine

• Additional analytes

• trazodone

• clonazepam • flunitrazepam

• bromazepam

• lorazepam

• temazepam

Chromatogram of Tricyclic Antidepressants from Calibrator A

Chromatogram of Benzodiazepines from Calibrator C

Chromatogram of Benzodiazepines from Calibrator B

Chromatogram of Benzodiazepines from Calibrator D

RAPsyD by HPLC (Reversed Phase)Application now easily compatible with Bio-Rad’s Benzo/TCA by HPLC assay due to use of the same analytical column, extraction cartridge and mobile phases

Bio-Rad’sapplicationforRapidAnalysisofPsychoactive

Drugs(RAPsyD)issuitableforreliable,fastandeasy

simultaneous quantitative measurement of clozapine,

olanzapine, quetiapine, risperidone, and their

pharmacologically active metabolites. The antipsychotics

areextractedandseparatedwithanHPLCmethodbyonlinecolumnswitchingbetweenanextraction

cartridge and an analytical column.

Test characteristics:• Principle:IsocraticHPLCmethod

• Durationofthechromatography:25min.

• Samplevolume:600mLserumorplasma

• Flowrate:0.8mL/min

• UVDetection:254nm(clozapine,olanzapine,quetiapine);278nm(risperidone)

min5 10 15 20 25

mAU

-1

0

1

2

3

4

5

6

7

Clo

zapi

ne

Inte

rnal

Sta

ndar

d 1

Que

tiapi

ne

Ola

nzap

ine

Nor

cloz

apin

e

min5 10 15 20 25

mAU

-1

0

1

2

3

4

5

6

7

Ris

perid

one

9-O

H-R

ispe

ridon

e

Zip

rasi

done

(inf

orm

atio

nal o

nly)

Inte

rnal

Sta

ndar

d 1

Chromatogram of Calibrator A, contains clozapine, norclozapine, olanzapine and quetiapine

Chromatogram of Calibrator C, contains risperidone and 9-OH risperidone

RAPsyD by HPLC

Benzodiazepines and Tricyclics by HPLC (Reversed Phase)

Reagent Kit

Catalog No. Description

195-6550 BenzodiazepinesandTricyclicsReagentKit ................................................................................................200tests

consisting of:

195-6686MobilePhase1Set .............................................................................................................................1 unit


195-6556StandardExtractionSet ......................................................................................................................1 unit

Additionally Required Items


195-6684 AnalyticalColumn(includesoneMicro-Guard™Cartridge). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .600injections

195-6685 ExtractionCartridge(incl.2prefilters) ....................................................................................................100injections

195-5030 Micro-Guard™CartridgeHolder ............................................................................................................................1 unit

195-6682 HolderforPrefilter .................................................................................................................................................1 unit

270-0613 HolderforExtractionCartridge ............................................................................................................................1 unit

Separately Available Items


195-6552 CalibratorA(mono-level) ................................................................................................................................1x5mL

195-6553 CalibratorB(mono-level) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1x5mL

195-6554 CalibratorC(mono-level) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1x5mL

195-6555 CalibratorD(mono-level) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1x5mL

195-6559 ControlASet(bi-level) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2x2x5mL

195-6562 ControlBSet(bi-level). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2x2x5mL

195-6565 ControlCSet(bi-level) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2x2x5mL

195-6568 ControlDSet(bi-level) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2x2x5mL

195-6686 MobilePhase1Set . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1x4mL

195-6687 MobilePhase2Set . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1x4mL

RAPsyD by HPLC (Reversed Phase)

Reagent Kit


195-6600 RAPsyDbyHPLCReagentKit ......................................................................................................................200tests

consisting of:



195-6634StandardExtractionSet ......................................................................................................................1 unit



195-6684 AnalyticalColumn(includestwoMicro-Guard™Cartridges) ..................................................................600injections

195-6685 ExtractionCartridge(incl.2prefilters) ....................................................................................................100injections


195-6682 HolderforPrefilter .................................................................................................................................................1 unit

270-0613 HolderforExtractionCartridge ............................................................................................................................1 unit

continued on the other side

Therapeutic Drug Monitoring Ordering InformationBio-Rad Laboratories T H E R A P E U T I C D R U G M O N I T O R I N G / T O X I C O L O G Y

For further information, please contact the Bio-Rad office nearest you or visit our website at www.bio-rad.com/diagnostics

© 2010 Bio-Rad Laboratories, Inc. Printed in Germany 08/10 EU-TDM-08/10E

Clinical Diagnostics Group

Website www.bio-rad.com/diagnostics U.S. 1-800-2BIO-RAD Australia 61-2-9914-2800 Austria 43-1-877-8901 Belgium 32-9-385-5511 Brazil 5521-3237-9400 Canada 1-514-334-4372 China 86-21-64260808 Czech Republic 420-241-430-532 Denmark +45-4452-1000 Finland 358-9-804-22-00 France 33-1-47-95-60-00 Germany +49-(0)89-318-840 Greece 30-210-7774396 Hong Kong 852-2789-3300 Hungary +36-1-459-6100 India 1-800-180-1224 Israel 972-3-9636050 Italy +39- 02-216091 Japan 81-3-6361-7070 Korea 82-2-3473-4460 Mexico +52 (55) 5488-7670 The Netherlands +31-318-540666 New Zealand 64-9-415-2280 Norway 47-23-38-41-30 Poland 48-22-3319999 Portugal 351-21-472-7700 Russia 7-495-721-14-04 Singapore 65-6415-3170 South Africa 27-11-442-85-08 Spain 34-91-590-5200 Sweden 46-8-555-127-00 Switzerland 41-61-717-95-55 Thailand 662-651-8311 United Kingdom +44-(0)20-8328-2000

T H E R A P E U T I C D R U G M O N I T O R I N G / T O X I C O L O G Y

Antiepileptics by HPLC

Reagent Kit


195-6210 AntiepilepticsbyHPLCReagentKit,ManualMethod ..................................................................................100tests

consisting of:

195-6210RReagentSet ......................................................................................................................................1 unit

195-6205CalibratorASet ...................................................................................................................................1 unit

195-6220 AntiepilepticsbyHPLCReagentKit,OnlineMethod ...................................................................................200tests

consisting of:

195-6220RReagentSet ......................................................................................................................................1 unit

195-6205CalibratorASet ...................................................................................................................................1 unit

195-6209MobilePhase2 ....................................................................................................................................1 unit



195-6206 AnalyticalColumn(includesoneMicro-Guard™Cartridge) ....................................................................500injections

195-6219 ExtractionCartridge,OnlineMethod ....................................................................................................................1 unit

270-0613 ExtractionCartridgeHolder ..................................................................................................................................1 unit


195-6682 PrefilterHolder ......................................................................................................................................................1 unit



195-5898 TestMix ...........................................................................................................................................................1x2mL

195-6205 CalibratorSetA(mono-level) ..........................................................................................................................2x1mL

195-5896 CalibratorSetB(mono-level) .........................................................................................................................2x1mL

195-6208 CalibratorSetC(mono-level) .........................................................................................................................2x1mL

195-6215 ControlASet(bi-level) ....................................................................................................................................2x1mL

195-6500 ControlBSet(bi-level) ....................................................................................................................................2x1mL

195-6218 ControlCSet(bi-level) ....................................................................................................................................2x1mL

195-6203G MobilePhase1 ...........................................................................................................................................1x800mL

195-6209 MobilePhase2 ...........................................................................................................................................1x800mL

195-6003 Micro-Guard™Cartridge(250injectionseach) ......................................................................................2perpackage

195-6636 HPLCPrefilter ........................................................................................................................................2perpackage

RAPsyD by HPLC (Reversed Phase) continued



195-6686 MobilePhase1Set ................................... 1x4mL

195-6687 MobilePhase2Set ................................... 1x4mL

195-6685 ExtractionCartridge(w/2prefilters) .........100inj

195-6607 CalibratorA(mono-level) ...........................1x5mL

195-6606 CalibratorC(mono-level) ................... 1x5mL

195-6677 ControlASet(bi-level) ....................... 2x5mL

195-6678 ControlCSet(bi-level) ...................... 2x5mL

abu therapeutic drug monitoring by hplc · by hplc (reversed phase) improved online application now...

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