The LC-MS/MS WorkhorseSCIEX 4500 Series Mass Spectrometers

The SCIEX 4500 Series takes the legendary API 4000™ platform and intelligently re-engineers it to set a new benchmark for reliable quantitation. It offers the quantitative sensitivity, robustness, and performance you need, powered with QTRAP® technology to open a world of valuable experiments beyond MRM for significant data quality improvements for your most challenging methods.

Whether your research is focused on ADME, regulated bioanalysis, food and environmental contaminant screening, targeted quantitative proteomics, or clinical research, the SCIEX 4500 Series covers your key performance criteria:

• Quantitative and qualitative sensitivity to detect low concentration analytes in challenging matrices

• Dynamic range to see low to high concentration levels

• Scan speed to clearly resolve similar analytes

• Ionization source flow range for liquid chromatography flexibility

• Uniquely designed to occupy less of your valuable lab space

All backed by the integrity and quality of the SCIEX brand.

SCIEX 4500 Series The LC-MS/MS workhorse, intelligently re-engineered.

Redesigned from the foundation of our industry standard triple quadrupole mass spectrometers, the

4500 Series introduces a new era of LC-MS/MS performance defined by fast, precise quantitation and

ultra-fast scan speeds. The system is ideal for UHPLC, and with available QTRAP technology you get

better data, and more of it, than you can achieve using basic multiple reaction monitoring (MRM) on

an ordinary triple quad system.

Fast LC demands short dwell times

Delivering dwell times as low as 1ms, the 4500 complements

UHPLC separations to screen for more compounds within a single

experiment than ever before. You can maximize your capacity

and deliver quality quantitation every time using the powerful

Scheduled MRM™ algorithm which automatically optimizes your

acquisition method.

Better data. Complete confidence. Unrivalled efficiency. Ultimate performance.

Only SCIEX offers triple quads equipped with Linear Accelerator™

Trap technology. The QTRAP® 4500 delivers up to a 100-fold

increase in full scan MS/MS sensitivity enabling powerful workflows

that will give you a new level of confidence in your data.

• Unique scan functionality available only on the QTRAP, allows

you to see beyond the matrix to more accurately detect,

quantify, and confirm your compounds

• Acquire a complete MS/MS spectrum to accompany your

MRM quantitation for every compound detected in your

samples and cross reference with an integrated library for

ultimate confirmation

• Screen for more compounds in each analysis, without

compromising data quality for higher throughput

RUO-MKT-03-0137-C

For Research Use Only. Not for use in diagnostic procedures.

Much More Than a Triple QuadThe 4500 Series is robustly designed to deliver reliable quantitation over long runs, and is the only

triple quad system in the world equipped with Linear Ion Trap (LIT) technology that can be unlocked

to deliver enhanced capabilities when you need it.

QTRAP® technology delivers better data, and more of it, than you can achieve using basic multiple

reaction monitoring (MRM) on an ordinary triple quad system.

Diversity delivered

With the quantitative performance of a triple quad system

and QTRAP’s additional enhanced scan functionality, you are

able to develop new methods and improve results for your

existing workflows.

See more clearly beyond the matrix

When your analysis suffers from matrix effects and you’re

concerned about the accuracy of your MRM quantitation,

QTRAP technology can reduce the worry. The integrated Linear

Ion Trap (LIT) enables more accurate detection, quantification,

and confirmation of your compounds – without added laborious

or time consuming sample prep.

More confidently identify your compounds

For borderline MRM ion ratios, resulting in ambiguous

identification, there is a solution. QTRAP’s enhanced product

ion (EPI) functionality allows you to acquire a complete

MS/MS spectrum to accompany your MRM quantitation for

every compound detected in your samples. Cross reference this

‘compound fingerprint’ with an integrated library, and deliver

ultimate confirmation and report your analysis without doubt.

More compounds and more samples

If your workload increases, but your time and resources don’t,

QTRAP delivers more results in every run. The unique ability to

capture MRM and enhanced product ion confirmation scans

in one injection, without the need for long and inefficient

chromatography, enables reliable screening for more compounds

in each analysis, without compromising data quality. This all leads

to better throughput, without investing more time and resources.

Definitive Quantitation and So Much More

For Research Use Only. Not for use in diagnostic procedures.

The Future Path of LC-MS/MS Quantitation

The SCIEX 4500 Series brings together the latest hardware

from the world’s best selling triple quadrupole family,

and adds next-generation, ultra-fast and sensitive Linear

Accelerator™ Trap functionality. Delivering unmatched

quantitative and qualitative analysis, the 4500 Series

enables productive, time-saving workflows unachievable

with other mass spectrometry systems.

Patented QJet® Ion GuideOptimized design yields better ion containment and operates at high

pressure. This provides better collisional focusing to enhance ion

transmission for improved sensitivity. The new design also lets the

turbopump run cooler and in its ideal operating range.

AcQuRate™ Pulse Counting Detector

The AcQuRate™ pulse counting detector combined with a pulse overlap

correction algorithm, enable more accurate and precise ion detection over

a wide dynamic range. Continuous operation at maximum gain drives the

detector into the digital domain, simplifying the elimination of electronic

noise and guaranteeing maximum sensitivity with unparalleled accuracy

and precision.

Proven Q0 High-Pressure CellThe high pressure collisional focusing technology maximizes transmission of

ions for superior sensitivity.

Ions can be accumulated in the Q0 region while the Linear Accelerator™

trap is performing MS/MS and MS3 scans. This yields superior sensitivity

in ion trap mode, which can be extremely important for fast UHPLC

applications where time and duty cycle are condensed.

Patented Qurved LINAC® Collision Cell The Qurved LINAC® high-pressure collision cell accelerates ions

through the cell to increase speed of analysis and eliminate cross-talk.

Improvements to the acclaimed LINAC collision cell result in shorter transit

times across the cell, making the Qurved LINAC cell an ideal match for

UHPLC and high throughput analysis focused on hundreds of compounds.

True collision-induced fragmentation with the Qurved LINAC collision cell

generates reliable, information-rich, library-searchable MS/MS spectra time

after time.

Fast eQ™ Electronics for Fast LCNext-generation eQ™ electronics produce polarity switching in 50 ms

and scan speeds of 20,000 Da/s. Now, compounds with vastly different

functional groups can be measured in a single pass. The new electronics

also improve ion containment for better sensitivity and superior detector

performance. Ultra-fast and ultra-stable instrumentation means you get

the most out of your standard or fast LC to save time and accelerate

your research.

Integrated QTRAP® technology LINAC® technology to the Q3 linear ion trap greatly improves extraction

efficiency to yield up to a 100X gain in sensitivity under ion trap scan modes.

Take full advantage of the 20,000 Da/s scan speeds with full scan linear ion

trap sensitivity – 100X more sensitive than triple quad full scan experiments

for greater confidence in qualitative workflows. Improved excitation efficiencies

and reduced ion cooling and fragmentation times produce superior MS3

qualitative results and provide unprecedented selectivity for the most

challenging analytical assays.

RUO-MKT-03-0137-C

For Research Use Only. Not for use in diagnostic procedures.

Robustness and Performance for Any Application

With dwell times as low as 1ms, the 4500 series is ideally suited for multi component contaminant analysis as these data demonstrate with the detection of over 200 pesticides at 1ng/mL. The faster electronics and the intelligent Scheduled MRM (sMRM), permits the screening of hundreds of pesticides in a UHPLC time scale.

Superior quantitative performance for sensitive, accurate, and reliable analysis in antiretroviral drug research.

Without compromising sensitivity, the SCIEX QTRAP 4500 System has improved in every category vs. the API 4000 including dynamic range, scan speed and footprint.

Highly multiplexed peptide quantitation using the Scheduled MRM™ algorithm.  30 selected MRM transitions from a 4000 MRM assay of tryptic peptides. This experiment was run in replicate on an Eksigent 200 um ID cHiPLC® column with peak area deviation < 10%. Insert: an example of multiple MRMs to a single peptide, showing selected fragment ion chromatograms.

Contaminant analysis Drug monitoring research

Drug discovery and development Peptide quantitation

1.0 2.0 3.0 4.0 5.0 6.0 7.0 8.0 9.0 10.0 11.0 12.0 13.0 14.0 15.0

Time, min

0.001.00e42.00e43.00e44.00e45.00e46.00e47.00e48.00e49.00e41.00e5

Inte

nsity

, cps

4.10

204 pesticide standard (1 ng/mL)

Lamivudine

Emtricitabine

Didanosine

Stavudine

Zidovudine

QT4500 spike6 NRTI.rdb (FTC 1): "Linear" Regression ("1 / x" weighting): y = 0.00204 x + -0.00116 (r = 0.9988)

0 500 1000 1500 2000 2500 3000 3500 4000 4500 5000Analyte Conc. / IS Conc.

0.0

0.5

1.0

1.5

2.0

2.5

3.0

3.5

4.0

4.5

5.0

5.5

6.0

6.5

7.0

7.5

8.0

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9.0

9.5

10.0

10.5

An

aly

te A

rea

/ I

S A

rea

!"#$%&%#'(%)*+,-./0102223)45"6

QT4500 spike6 NRTI.rdb (FTC 1): "Linear" Regression ("1 / x" weighting): y = 0.00204 x + -0.00116 (r = 0.9988)

0 500 1000 1500 2000 2500 3000 3500 4000 4500 5000Analyte Conc. / IS Conc.

0.0

0.5

1.0

1.5

2.0

2.5

3.0

3.5

4.0

4.5

5.0

5.5

6.0

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7.5

8.0

8.5

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9.5

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10.5

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aly

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/ I

S A

rea

Emtricitabine (FTC)5-5000 ng/mL

0.2 0.4 0.6 0.8 1.0 1.2 1.4 1.6 1.8 2.0 2.2 2.4 2.6 2.8 3.0 3.2 3.4 3.6 3.8

Time, min

3.3e63.2e63.1e63.0e62.9e62.8e62.7e62.6e62.5e62.4e62.3e62.2e62.1e62.0e61.9e61.8e61.7e61.6e61.5e61.4e61.3e61.2e61.1e61.0e69.0e58.0e57.0e56.0e55.0e54.0e53.0e52.0e51.0e50.0e0

Inte

nsity

, cps

0.548

API 4000 Triple Quad™ 4500 system

Time, min Time, min

Inte

nsity

Inte

nsity

2.5e52.4e52.3e52.2e52.1e52.0e51.9e51.8e51.7e51.6e51.5e51.4e51.3e51.2e51.1e51.0e59.0e48.0e47.0e46.0e45.0e44.0e43.0e42.0e41.0e40.0e0

2.5e52.4e52.3e52.2e52.1e52.0e51.9e51.8e51.7e51.6e51.5e51.4e51.3e51.2e51.1e51.0e59.0e48.0e47.0e46.0e45.0e44.0e43.0e42.0e41.0e40.0e0

0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5

1.0 1.4 1.8 2.2 Time, min

5e4

Inte

nsity

, cps

Q3 m/z 416 725 1423 1698 1816

10 15 20 25 30 35

Time, min

100

Inte

nsity

, cps

For Research Use Only. Not for use in diagnostic procedures.

QTRAP® 4500 System

MRM3—Enhanced selectivity

Reactive metabolite screening

High confidence library searching capabilities

Qual-Quant: detection and confirmation

Quantitation of tryptic peptides in a complex matrix. Higher selectivity workflows such as MRM3 (bottom) can provide additional specificity for low level detection of compounds when high background or interferences render MRM workflows ineffective (top).

Combining intelligent peak detection with the ability to trap and scan out ions on a UHPLC time scale, creates a potent solution for detecting unexpected contaminants. Add to this a single library of thousands of QTRAP spectra for library matching, and contaminants at the lowest levels can be confidently identified.

Troglitazone GSH adduct was detected using complimentary positive neutral loss and negative precursor ion scans, combined with Information Dependent Acquisition (IDA) linear ion trap scans. This unique workflow results in the comprehensive detection and characterization of GSH adducts in a single injection.

The QTRAP 4500 system allows Scheduled MRM (sMRM) to trigger high quality, full scan product ion spectra for use in library searching. With highly sensitive Triple Trap™ scanning it is possible to confidently identify compounds at up to 100X lower concentrations than triple quadrupole full scans.

20.6 21.0 21.4 21.8

Time, min

10021.1

21.36

MRM3

Sum of fiveMS/MS/MS ions

Inte

nsity

, cps

In

tens

ity, c

ps

100

21.1

MRM

2y52y42y6

80 90 100 110 120 130 140 150 160 170 180 190 200 210 220 230 240 250 260 270 280

m/z, Da

0.00

5.00e4

1.00e5

1.50e5

2.00e5

2.50e5

3.00e5

3.50e5

4.00e5

4.50e5

5.00e5

5.50e5

6.00e5

6.50e5

7.00e5

7.50e5

8.00e5

8.50e5

9.00e5

9.50e5

1.00e6

Inte

nsity

, cps

160.1

192.1

132.0105.0

117.0 134.090.0 106.0 149.092.0

Compound identification with high confidence using MS/MS library searching

67 ng/mL Carbendazim in orange juice (FIT = 97%)

Inte

nsity

Inte

nsity

Inte

nsity

735 740 745 750 755 760 765 770 775 780 7850e01e52e53e54e55e56e57e58e59e5 747.3

748.3

749.3

750.3

1.17

3.77

100 150 200 250 300 350 400 450 500 550 600 650 700 750

Mass/Charge, Da

0.0e02.0e64.0e66.0e68.0e61.0e71.2e71.4e71.6e71.8e72.0e72.2e7 308.1

179.1162.0

233.1

747.3309.1217.1440.2143.9

234.9 618.3

+NL of 129 and – Prec of m/z 272 scans with fast polarity switching

Enhanced resolution

Enhanced product ion scan obtained in IDA mode

Time, min

Mass/Charge, Da

0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 6.5

5.5e55.0e54.5e54.0e53.5e53.0e52.5e52.0e51.5e51.0e55.0e4

0e0

0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5Time, min

0.0

5.0e5

1.0e6

1.5e6

2.0e6

2.5e6

3.0e6

3.5e6

4.0e6

4.5e6

5.0e6

5.5e6

Inte

nsity

, cps

• 6 minute run time • 2.2 mL/min flow rate • Monitoring 256 drugs • ~5 sec wide peaks

60 80 100 120140 160180200220 240 260 280300320340360380400420440460 4800.0

1.0e4

2.0e4

3.0e4

4.0e4

5.0e4

6.0e4

7.0e4

8.0e4

9.0e4

1.0e5

1.1e5

1.2e5

1.3e5

1.4e5 337.2

188.2

105.2

Fentanyl

sMRM survey scan for Quant

60 80 100 120 140 160 180 200 220 240 260 280 300 320 340 360 380 400 420 440 460 4800.0

5000.0

1.0e4

1.5e4

2.0e4

2.5e4

3.0e4

3.5e4

4.0e4

4.5e4

5.0e4

5.5e4

6.0e4

6.5e4

7.0e4

7.5e4

8.0e48.2e4 265.2

310.2

104.9

159.1219.2116.9

203.3167.2

Methadone

60 80 100 120 140 160 180 200 220 240 260 280 300 320 340

m/z, Da

0.0

1.0e5

2.0e5

3.0e5

4.0e5

5.0e5

6.0e5

7.0e5

8.0e5

9.0e5

1.0e6

1.1e6

1.2e6

1.3e6

1.4e6

Inte

nsity

, cps

m/z, Da

Inte

nsity

, cps

m/z, Da

Inte

nsity

, cps

302.2

284.2

227.2

198.2

242.2161.0181.1

173.3224.2

214.2146.2 188.2 256.2201.1 266.2240.2153.2 211.6144.0132.1

Oxymorphone

Example Triggered Product Ion Spectra For Library Searching

QTRAP® Technology – Unmatched Versatility and Confidence

RUO-MKT-03-0137-C

The excellent reproducibility

for the peak area ratio of

Methamphetamine and

Amphetamine in human

plasma shows the stability

of the AcQuRate™ pulse

counting detector for

consistent quantification

Ultimate sensitivity and simplicity

The patented QJet® ion guide improves

ion containment and operates at high

pressure, providing better collisional

focusing to enhance ion transmission for

ultimate sensitivity. The proven design

also reduces the gas load, allowing the

turbopump to run cooler in its ideal

operating range. It all adds up to our

most reliable system – and with tool-free

maintenance, clean-up is simple

and straightforward.

Nanoflow made easy

The NanoSpray® III ion source makes

working with nanoflow chromatography

easy while providing the highest sensitivity

and stability. The NanoSpray III source

supports regular and column-packed

emitter tips for ultimate chromatographic

flexibility. The camera design allows

clear spray visualization for simplified

optimization. Fingertight fittings enable you

to change tips quickly, so you are up and

running in no time.

Drive productivity

The Turbo V™ source provides

high-sensitivity analysis over a wide range

of flow rates with quick-change APCI and

TurboIonSpray® probes. From 50 μL/min

to 3 mL/min, the Turbo V Source is the

perfect match for narrow bore, standard

bore and UHPLC flow rates, delivering

unprecedented desolvation and stability for

even the toughest high-flow applications.

Injection Number

Robustness Test in Plasma: 1500 Injections

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For Research Use Only. Not for use in diagnostic procedures.

One Touch ProductivityTake full advantage of all the speed and power of the 4500 Series. Powerful, workflow-driven

software ties everything together efficiency, throughput, and productivity. Industry-standard Analyst®

Software utilizes the intelligent Scheduled MRM™ algorithm to make the method setup of over

1000 analytes in a single LC analysis straightforward and simple while still generating exceptional

quantitative and brilliant qualitative results.

Instrument control, analysis, and reporting

Analyst® Software

provides state-of-the-art

functionality for instrument

control, data analysis, and

reporting. The latest version builds on this legacy by providing

new features that enhance both performance and ease of use.

Save time, without compromising

Complete metabolite coverage

LightSight® Software

simplifies analysis of

complete metabolite

coverage. Create expert-

level acquisition methods in

just a few simple steps using the automated method development

tool. Alternatively, take advantage of customized glutathione

screening to quickly identify potential reactive metabolites and

significantly increase metabolite detection with targeted methods.

MRM data processing

MultiQuant™ Software is

a powerful, easy-to-use

package that processes

MRM data for quantitative

information. The software

handles large data sets

consisting of both large numbers of MRM transitions and study

samples, with an emphasis on the requirements for processing

protein/peptide quantitative workflows. Results are easily exported

to other software packages, or use the software’s flexible reporting

features to generate custom reports.

Fast multi-component screening

With a simplified user-

interface and streamlined

workflows, MasterView™

Software enables you to

process your QTRAP® MS/

MS screening data faster, with improved confidence beyond MRM

detection alone. The integration of MS/MS compound libraries and

customizable data review settings, screen for more compounds in

more samples faster and more reliably than ever before– reducing

your data processing time to minutes. MasterView Software is

ideal for routine food, environment, and forensic labs testing high

volumes of samples in complex matrices and requiring the highest

confidence in compound identification.

RUO-MKT-03-0137-C

AB Sciex is doing business as SCIEX.

© 2016 AB Sciex. For Research Use Only. Not for use in diagnostic procedures. The trademarks mentioned herein are the property of AB Sciex Pte. Ltd. or their respective owners. AB SCIEX™ is being used under license.

10/2016 RUO-MKT-03-0137-C

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