The LC-MS/MS Workhorse. SCIEX 4500 Series Mass Spectrometers

Transcription

1 The LC-MS/MS Workhorse SCIEX 4500 Series Mass Spectrometers

2 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.

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

4 Much More Than a Triple Quad The 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.

5 For Research Use Only. Not for use in diagnostic procedures. Definitive Quantitation and So Much More 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. 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. 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

6 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. 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. Patented QJet Ion Guide Optimized 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. Proven Q0 High-Pressure Cell The 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 MS 3 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.

7 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 MS 3 qualitative results and provide unprecedented selectivity for the most challenging analytical assays. For Research Use Only. Not for use in diagnostic procedures. 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 LC Next-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. RUO-MKT C

8 For Research Use Only. Not for use in diagnostic procedures. Robustness and Performance for Any Application Contaminant analysis Drug monitoring research 1.00e5 9.00e4 8.00e4 7.00e4 6.00e4 5.00e4 4.00e4 3.00e4 2.00e4 1.00e pesticide standard (1 ng/ml) e6 3.2e6 3.1e6 3.0e6 2.9e6 2.8e6 2.7e6 2.6e6 2.5e6 2.4e6 2.3e6 2.2e6 2.1e6 2.0e6 1.9e6 1.8e6 1.7e6 1.6e6 1.5e6 1.4e6 1.3e6 1.2e6 1.1e6 1.0e6 9.0e5 8.0e5 7.0e5 6.0e5 5.0e5 4.0e5 3.0e5 2.0e5 1.0e5 0.0e Lamivudine Emtricitabine Didanosine Stavudine Emtricitabine!"#$%&%#'(%)*+,-./ (FTC) )45"6 ng/ml Zidovudine 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. Drug discovery and development Peptide quantitation API 4000 QTRAP Triple Quad System system 100 5e4 Q3 m/z Intensity 2.5e5 2.4e5 2.3e5 2.2e5 2.1e5 2.0e5 1.9e5 1.8e5 1.7e5 1.6e5 1.5e5 1.4e5 1.3e5 1.2e5 1.1e5 1.0e5 9.0e4 8.0e4 7.0e4 6.0e4 5.0e4 4.0e4 3.0e4 2.0e4 1.0e4 0.0e0 2.5e5 2.4e5 2.3e5 2.2e5 2.1e5 2.0e5 1.9e5 1.8e5 1.7e5 1.6e5 1.5e5 1.4e5 1.3e5 1.2e5 1.1e5 1.0e5 9.0e4 8.0e4 7.0e4 6.0e4 5.0e4 4.0e4 3.0e4 2.0e4 1.0e4 0.0e Intensity 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.

9 1.4e6 1.3e6 1.2e6 1.1e6 1.0e6 9.0e5 8.0e5 7.0e5 6.0e5 5.0e5 4.0e5 3.0e5 2.0e5 1.0e e5 1.3e5 1.2e5 1.1e5 1.0e5 9.0e4 8.0e4 7.0e4 6.0e4 5.0e4 4.0e4 3.0e4 2.0e4 1.0e e4 7.0e4 6.5e4 6.0e4 5.5e4 5.0e4 4.5e4 4.0e4 3.5e4 3.0e4 2.5e4 2.0e4 1.5e4 1.0e QTRAP Technology Unmatched Versatility and Confidence MRM 3 Enhanced selectivity High confidence library searching capabilities MRM 3 Sum of five MS/MS/MS ions MRM 2y5 2y4 2y e6 9.50e5 9.00e5 8.50e5 8.00e5 7.50e5 7.00e5 6.50e5 6.00e5 5.50e5 5.00e5 4.50e5 4.00e5 3.50e5 3.00e5 2.50e5 2.00e5 1.50e5 1.00e5 5.00e Compound identification with high confidence using MS/MS library searching ng/ml Carbendazim in orange juice (FIT = 97%) m/z, Da Quantitation of tryptic peptides in a complex matrix. Higher selectivity workflows such as MRM 3 (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. Reactive metabolite screening Qual-Quant: detection and confirmation Intensity Intensity 5.5e5 5.0e5 4.5e5 4.0e5 3.5e5 3.0e5 2.5e5 2.0e5 1.5e5 1.0e5 5.0e4 0e0 +NL of 129 and Prec of m/z 272 scans with fast polarity switching e e7 1.8e e7 1.4e7 1.2e7 1.0e e6 6.0e e6 2.0e e Intensity Enhanced product ion scan obtained in IDA mode 9e e5 7e5 6e5 Enhanced 5e resolution 4e5 3e5 2e e e Mass/Charge, Da Mass/Charge, Da smrm survey scan for Quant 5.5e6 5.0e6 4.5e6 4.0e6 3.5e6 3.0e6 2.5e6 2.0e6 1.5e6 1.0e6 5.0e minute run time 2.2 ml/min flow rate Monitoring 256 drugs ~5 sec wide peaks Oxymorphone m/z, Da Fentanyl m/z, Da Example Triggered Product Ion Spectra For Library Searching 8.2e e4 Methadone m/z, Da 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. RUO-MKT C

10 For Research Use Only. Not for use in diagnostic procedures. 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. 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. Response Peak Area (counts) Robustness Test in Plasma: 1500 Injections 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 Injection Number

11 One Touch Productivity Take 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. Save time, without compromising 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 userinterface 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. Complete metabolite coverage LightSight Software simplifies analysis of complete metabolite coverage. Create expertlevel 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. 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. RUO-MKT C

12 Your Success is Our Success We take it personally As a SCIEX customer you have access to a world-class customer support organization. Wherever you are, we re there with you as a trusted partner to answer questions, provide solutions, and maximize lab productivity. Our customer support organization has access to the latest product updates, software revisions, methods and repair procedures to make sure that you stay on top of your game. When you have questions, we have answers. Learn more at sciex.com/customersupport, or locate your local account representative at sciex.com/contactus AB Sciex is doing business as SCIEX 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 C Headquarters 500 Old Connecticut Path Framingham, MA USA Phone sciex.com International Sales For our office locations please call the division headquarters or refer to our website at sciex.com/offices