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The New AB SCIEX QTRAP® 4500 and Triple Quad™ 4500 Systems Setting a New Benchmark for Ruggedness and Performance in Bioanalysis

Hesham Ghobarah Toronto, Canada Ruggedness and high throughput are key requirements for successful bioanalysis. The legendary API 4000™ system from AB SCIEX has been the gold standard in bioanalysis for over a decade, setting the benchmark in ruggedness, reliability, and performance. Through intelligent re-engineering, the AB SCIEX QTRAP® 4500 and Triple Quad™ 4500 Systems build on the legendary reliability of the API 4000™ and 4000 QTRAP® systems while adding advanced new capabilities for best-in class performance.

With intelligent engineering, the 4500 systems set a new standard in performance and reliability while protecting your investment in methods and training on the API 4000. Achieve advanced capability without sacrificing backward compatibility in method transfer, software, and training.

Key Benefits of the QTRAP® 4500 and Triple Quad™ 4500 Systems for Bioanalysis • Smaller footprint – efficient use of precious lab space

• m/z 5 - 2000 mass range – flexibility for small molecules and peptides

• QJet® 2 Ion guide – Proven ruggedness and sensitivity while

reducing vacuum load

• Faster MRM dwell times – monitor multiple analytes and internal standards with very sharp UHPLC peaks

• Faster polarity switching – pos/neg switching under UHPLC conditions

• Vastly improved MRM3 capability – powerful tool to increase selectivity

• Single turbo pump – Increased reliability of vacuum system

Figure 1. Ion Path Design. The new QTRAP® 4500 system ion path combines the elements of ruggedness, sensitivity, and extended mass range. QJet® 2 ion guide achieves robust operation while maximizing ion focusing. The space saving ion path achieves highest speeds for MRM and full scan analysis with an extended mass range of m/z 5 – 2,000.

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Ion Path Design – Proven Ruggedness and High Performance Based on the advanced ion path design and fast electronics of the QTRAP® 5500 system, the 4500 system achieves extended mass range, rock-solid ruggedness, high sensitivity, and vastly improved MRM3 performance (Figure 1).

Figure 2. Interface Ruggedness. Combined with the Turbo V™ source and Curtain Gas™ interface, the QJet® 2 ion guide demonstrates excellent ruggedness for large batches of protein precipitated plasma samples.

The QJet® 2 ion guide maximizes ion transfer and sensitivity while maintaining very high ruggedness. This design is superior to other interface designs as it actually reduces vacuum load while increasing ion transmission. As a result, only one turbo pump is required resulting in high reliability and quiet operation (Figure 2).

Extended mass range of m/z 5 – 2,000 (quad scans) and m/z 50 – 2,000 (trap scans) is achieved by using an optimized RF drive frequency (940 kHz) while maintaining excellent low mass ion confinement. As a result, excellent sensitivity is achieved for both small molecule and peptide quantitation (Figures 3,4).

Figure 3. Excellent High Mass Sensitivity for Peptide Quantitation. The QTRAP® 4500 system demonstrates up to 3x signal gains with an extended mass range of m/z 5 – 2,000.

Figure 4. Low Mass Sensitivity. Extended mass performance is achieved without compromise of small molecule sensitivity.

The fast electronics achieve full UHPLC compatibility through fast MRM dwell times (2 ms), and fast positive negative polarity switching (50 ms) which allows polarity switching to be performed for multiple analytes on a UHPLC time scale.

The QTRAP® 4500 achieves major improvements in linear ion trap sensitivity, speed and fragmentation efficiency which results in vastly improved MRM3 performance. This provides the bioanalytical scientist with a powerful tool to solve tough

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Response 2.1% CV

Response 3.5% CV

ISTD Corrected 1.6% CV

ISTD Corrected 2.9% CV

XIC of +MRM (6 pairs): 1166.100/1423.600 Da ID: Frag 1423 from Sample 4 (100fmol/uL Insulin) o... offset by 0.04 min

Max. 8523.8 cps.

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XIC of +MRM (8 pairs): 786.100/813.400 Da ID: Frag 813 from Sample 13 (Glu-Fib MRM-100 fmol/u... Max. 1.8e4 cps.

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selectivity challenges (Figure 5). With the 4500 system, methods can be easily transferred from the 4000 QTRAP® system, and there is no need to learn new software.

Figure 5. Trap Sensitivity. Vastly improved linear ion trap sensitivity and speed achieved by the Linear Accelerator™ Trap, with up to 50x improvement at faster scan speed.

Accelerated Lab Integration™ Package for Bioanalysis AB SCIEX provides the total solution package for rapid and cost effective implementation in the regulated bioanalytical laboratory. Software and professional validation services are an integral part of the ALI™ package for bioanalysis. Analyst® and MultiQuant™ software are powerful and trusted platforms in regulated bioanalysis. Validation of new software can be time consuming and costly, posing a barrier to implementation. With validation services from AB SCIEX™, software validation is performed on-site and to your requirements by experienced validation professionals. A comprehensive range of validation services is available, providing an integrated approach to hardware qualification and software validation from a single vendor. This takes the pain out of validation and results in being able to place new instruments and software into production rapidly, while realizing maximum benefit from your investment.

MultiQuant™ Software MultiQuant software was designed for the bioanalytical laboratory with the goal of improving efficiency and facilitating compliance through an easy-to-use interface and powerful functions. Integrated within Analyst® software, the user has the ability to use the same access controls and user roles that have been configured in Analyst Software. This greatly simplifies install administration, access management, and ensuring uniform data processing and review privileges.

Figure 6. Powerful Audit Trail Viewer in MultiQuant. The viewer displays events and the associated data with hyper-linking. The data is shown before and after each audited event. The reviewer can quickly spot the impact of a change. Results tables and peak review are automatically linked to the audit trail.

Key Features of MultiQuant Software for Regulated Bioanalysis • Fast and user friendly interface with linked panes, custom

queries and one click metric plots.

• New audit trail with robust management and precise control.

• All versions of the calculated results are stored, and hyperlinked to the audit trail which allows the reviewer to quickly see the data before and after a change.

• Results table locking feature and secure export.

• Audit trail allows search for specific events or samples across all results tables within a project, allowing easier QA review

Conclusions • The AB SCIEX QTRAP® 4500 and Triple Quad™ 4500

systems build on the legendary reliability of the API 4000™ and 4000 QTRAP® systems, while adding advanced new capabilities for best-in class performance.

• An extended mass range of m/z 5 – 2,000 provides maximum flexibility for bioanalysis of both peptides and small molecules without compromising sensitivity.

• Accelerated Lab Integration™ Package for Bioanalysis provides a complete hardware, software, and validation solution for cost effective adoption of new technology.

• MultiQuant™ software is easy to use with powerful compliance features such as searchable audit trail, storing all versions of data, and results locking after data review to insure data integrity.

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References 1. High Selectivity Quantification of Protein Isoforms using

MRM3 Workflow. AB SCIEX Technical Note, Publication 5190212-01.

2. MultiQuant™ Software 2.0: The New Standard in Productivity and Compliance for the Regulated Bioanalytical Laboratory. AB SCIEX Technical Note, Publication 1060210-01.

3. To download a trial version of MultiQuant™ Software please visit: www.absciex.com/multiquant

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

© 2012 AB SCIEX. The trademarks mentioned herein are the property of AB Sciex Pte. Ltd. or their respective owners. AB SCIEX™ is being used under license.

Publication number: 5270412-01