Mass Spectrometry Solutions for Qualitative and Quantitative Analysis. Best in Class. High performance advanced LC/MS/MS systems

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Mass Spectrometry Solutions for Qualitative and Quantitative Analysis Best in Class High performance advanced LC/MS/MS systems

Applied Biosystems/MDS SCIEX provides unparalleled performance for identification, characterization and quantitation of small molecules in a wide range of applications including drug development and discovery, metabolomics, clinical research, food analysis, environmental analysis, forensics and toxicology.

An Introduction to Mass Spectrometry LC/MS is a powerful analytical technology that offers substantial benefits. There are four basic components that make up a Mass Spectrometry instrument. Applied Biosystems/MDS SCIEX has worked at the forefront of the industry to innovate and develop the most advanced technological solutions in each of these components in order to deliver the most powerful systems available to our customers. SAMPLE INTRODUCTION I. ION SOURCE Creates charged ions II. VACUUM INTERFACE III. MASS ANALYZER Separates the ions in space or time based on their m/z ratio. IV. DETECTOR Counts the electrons generated from the ions V. DATA ANALYSIS Figure 1. Stages of the Mass Spectrometry Process In LC/MS, the sample is first separated with HPLC, and then Mass Spectrometry is used for detection. The Mass Spectrometer does this by producing charged particles (ions) from the analytes in the sample and using electric and/or magnetic fields to separate the charged particles according to their massto-charge (m/z) ratio. The resulting data are processed and analyzed by a data management system. The stages of this process are described above in Figure 1.

I. THE ION SOURCE After introduction of the sample from the HPLC system, the sample is ionized by the ion source. Types of sources include electron impact ionization (EI), chemical ionization (CI) and atmospheric pressure ionization (API). In LC/MS, the most common source is API, in which the mobile phase and sample are ionized at atmospheric pressure and the analyte ions are introduced into the mass spectrometer. There are three commonly used API methods: Electrospray Ionization (ESI) produces analyte ions in the liquid phase before they enter the Mass Spectrometer. It is used for polar small molecules, peptides, proteins, and oligonucleotides and other high molecular weight compounds. See Figure 2. Atmospheric Pressure Chemical Ionization (APCI) evaporates the sample through a heated nebulizer before ionization using plasma discharge. APCI is often used for thermally stable molecules that require more ionization energy. See Figure 3. Atmospheric Pressure Photo Ionization (APPI) is similar to APCI, except it uses photons to ionize the analyte molecules, and applies more ionization energy. This can lead to better detection limits for low-polarity compounds. See Figure 6. API Sources offered by Applied Biosystems/MDS SCIEX Electrospray Ionization (ESI) TurboIonSpray source (Figure 2), an IonSpray source with hot drying gas and flow rate from 2-1000 µl/min NanoSpray source, for improved sensitivity at lowest flow rates MicroIonSpray source, for very low flow rate up to 2 µl/min IonSpray source, a pneumatically assisted electrospray with flow rate from 2-200 µl/min Atmospheric Pressure Chemical Ionization (APCI) The Heated Nebulizer Source (Figure 3) is useful for small polar and neutral compounds. Combined Sources Combined sources offer analytical flexibility The Turbo V Source (Figure 4) has exchangeable probes for ESI and APCI The DuoSpray Source (Figure 5) allows simultaneous or sequential use of ESI and APCI. Works equally well in positive and negative ion modes LC Effluent Nebulizer Gas High Voltage N 2 Atmospheric pressure Chemical Ionization X = solvent molecules, e.g. H 2 O, NH 3, etc. Nebulizer Gas 1. Ionization produces predominantly solvent ions Sample (M) 3. the Curain Gas helps transfer ions to the mass analyzer and effects ion declustering Curtain Gas LC Effluent Heated Turbo-Probe Turbulent Mixing N 2 Make-up Gas (~120 C) Corona Discharge Needle 2. the reagent ions react with analyte molecules, forming clusters Curtain Gas Figure 2. TurboIonSpray Source Figure 3. Heated Nebulizer Source

II. THE VACUUM INTERFACE The vacuum interface ensures the transition of ions from the API source to the mass analyzer, which is kept under vacuum. Curtain Gas Interface The Curtain Gas interface protects the interface region from contamination and improves LC/MS productivity by blowing a reverse stream of nitrogen into the ion stream, creating a curtain that prevents the ions from striking the curtain plate and being neutralized. Atmospheric Pressure Photo Ionization (APPI) The PhotoSpray Source (Figure 6) provides greater ionization efficiency for low-polarity compounds TurboIonSpray Heater TurboIonSpray Inlet APCI Inlet IonSpray Probe Corona Discharge Needle Figure 5. DuoSpray Source Heater UV Lamp Curtain Plate Heater Gas Nebulizer Gas (Gas) Quartz Tube Heater Orifice Orifice Spray LC Effluent Exhaust Dopant PhotoSpray Source Block Primary Ionization Region Curtain Gas Figure 4. The Turbo V Source Figure 6 PhotoSpray Source

III. THE MASS ANALYZER From the ion source, ions are transferred to the mass analyzer where they are separated according to their mass-to-charge (m/z) values. The mass analyzer operates under a vacuum to ensure that ions travel with maximum efficiency. There are several types of mass analyzers: Quadrupole Systems Quadrupole mass analyzers use four parallel electrode rods arranged in a square to generate electrical fields that filter ions based on their mass-to-charge ratio as they travel through the rods. At particular magnitudes and frequencies, only ions of selected mass reach the detector. By consistently altering the electric fields, the masses of all ions can be scanned sequentially from low mass to high mass or vice-versa to give a mass spectrum. Time-of-Flight (TOF) Analyzers TOF analyzers apply a constant electrical field to all ions and measure the time the ions fly before reaching the detector. The relation between time and m/z ratio gives the mass of the ion. The heavier the ion, the slower it travels; the lighter it is, the faster it travels. Ion Trap Systems Ion trap systems use a spherical electrode to produce an electrical field that captures ions as they enter. Trapped ions are processed in a 3-dimensional oscillating field from which they can be released selectively. These systems are known as 3-D ion traps. Applied Biosystems/MDS SCIEX created a major breakthrough by introducing Linear Ion Trap where a quadrupole is used to trap ions thereby considerably increasing the trapping capacity and hence dramatically increasing sensitivity. Tandem MS Systems Mutiple-stage or tandem MS (MS/MS), is a technique in which mass analyzers are used in series to obtain structural information or to improve quantitative results. In a hybrid system, a TOF system or a linear ion trap replaces the third quadrupole (Q3) of a triple quadrupole to form the QqTOF (quadrupole-tof) and Q TRAP system technologies. Description of the Different Scan Modes in MS/MS Operation In MS/MS operation, different scan modes can be used to get complementary information about the sample. These modes are chosen and programmed using the system software. Product Ion Scan Provides structural information and identification of fragment ions Precursor Ion Scan Determines the origin of particular product ion(s) created in the collision cell and is frequently used for drug metabolite identification Constant Neutral Loss Indicates which ions lose a neutral species equal to Q1 Q3 difference Multiple Reaction Monitoring (MRM) Used primarily for quantitation studies, this mode allows monitoring of multiple precursor-to-product ion pairs and is the best way to maximize signal/noise ratio of compounds The LINAC Collision Cell A common problem in tandem MS systems is that the residence time of the ions (fragments) in the collision cell can initiate a phenomenon in Q3 called cross-talk, when ions of the same mass for multiple reactions are present. The patented LINAC Collision Cell solves this problem by using a field gradient to accelerate the fragment ions towards Q3. This offers a number of advantages, including: Multiple component analysis Small dwell times Conformation ions No loss of sensitivity Easier method development

IV. THE DETECTOR The detector measures the abundance of electrons generated from the ions for each m/z ratio. Most MS systems use some type of electron multiplier as a detector in combination with a signal amplifier. A record of all the charges detected during a scan constitutes a mass spectrum. Applied Biosystems/MDS SCIEX LC/MS/ MS instruments are all equipped with a Pulse Counting detector. This detection mode ensures that the true ion flux is collected as raw data. In contrast, many vendors use analog-mode detectors requiring both electronic and software noise rejection. This filtering of the signal prior to storage as raw data can have a dramatic effect on the data quality making poor data look better than it actually is. Understanding the detector operation is tremendously important for evaluating and conducting high performance LC/MS quantitative analysis. V. DATA ANALYSIS The data system provides a single point of control for the instrumentation, data acquisition, analysis and archiving, and spectrum searching. Following are the complete suite of mass spectrometry software that Applied Biosystems/MDS SCIEX offers: Analyst Software Applied Biosystems/MDS SCIEX Analyst software offers powerful tools for automating method development, data analysis, review, and reporting: Information Dependent Acquisition (IDA) automates MS to MS/MS acquisition for identification and characterization of metabolites and degradation products Automaton automates routine quantitative analysis methods Metabolite ID automates the acquisition and processing of relevant information for metabolite profiling Full scripting capability for customized software solutions Available on all triple quadrupole and hybrid linear ion trap systems from Applied Biosystems/MDS SCIEX Analyst software also helps laboratories working in regulated environments by providing easy database searching, traceability, security, and tools for 21 CFR Part 11 compliance Analyst QS Software Analyst QS software includes all Analyst Software functions for data acquisition and processing on the QSTAR Elite LC/MS/MS system, plus specific tools for the TOF technology such as: Internal, external TOF calibration Calculation of elemental composition and isotopic distribution using mass accuracy Automatic compression of stored data MarkerView Software MarkerView software is used for metabolomics and biomarker profiling using data acquired on Applied Biosystems/ MDS SCIEX mass spectrometers to: Perform chromatographic and special peak picking to find true peaks in complex samples Align mass and retention time to compensate for minor variations and ensure accurate comparison of identical compounds in different samples Process data using classified and/or non-classified workflows with principal component analysis and t-tests to accelerate biomarker discovery Link to raw mass spectra and extracted ion chromatograms to support identification of putative biomarkers Automatically create reports on potential biomarkers and export data to thirdparty statistical packages for additional data mining

TM Mass Spectrometry Systems from the Leader in Life Science MS TRIPLE QUADRUPOLE LC/MS/MS SYSTEMS The API 2000 LC/MS/MS System The Entry-level System for Routine Laboratories The API 2000 LC/MS/MS System is an integrated, compact benchtop, easy-to-use triple quadrupole mass spectrometer for demanding, routine laboratories. This entry-level system features patented Applied Biosystems/MDS SCIEX API technology, with easy-tochange, plug-and-play ion sources for maximum flexibility in a wide range of applications. Other features include: Curtain Gas interface technology for unmatched ruggedness and reliability LINAC collision cell technology for fast scan times without cross-talk Full MS/MS capability for selectivity and sensitivity with Product Ion, Precursor Ion, Neutral Loss and MRM scans and a mass range up to 1800 m/z Analyst software for fully automated method optimization and exceptional ease-of-use The API 3200 LC/MS/MS System An Affordable Benchtop Platform Built on Premier Technology The fully integrated API 3200 LC/MS/MS system takes advantage of proprietary mass spectrometry innovations to deliver the performance required by demanding applications in regulated environments. Designed for high-throughput labs doing small molecule quantitation, this compact system delivers best-in-class reliability and reproducibility over virtually all sample types and concentrations encountered in environmental, food, clinical research and pharmaceutical applications. Like our industry-leading API 5000 and API 4000 systems, the API 3200 system provides an impressive array of high-performance features, including: Innovative Turbo V ion source with plug-and-play probes for efficient ionization and high sensitivity quantitation over a wide range of flow rates LINAC collision cell technology for faster scan times Curtain Gas interface for reduced maintenance and maximum productivity High-productivity software applications, including automated methods development Advanced acquisition and processing Analyst software for automated set-up and analysis Orifice Skimmer IQ1 Q1 Q2 Q3 Optional DuoSpray ion source for fast method development and increased throughput Source Q0 High Pressure Cell ST ST2 ST3 Q1 LINAC Collision Cell Q3 EXIT LENS IQ2 IQ3 DETECTOR CEM Optional PhotoSpray source expands the range of compounds for analysis Curtain Gas Interface Optional NanoSpray source for improved sensitivity at lowest flow rates

The API 4000 LC/MS/MS System The Industry Standard for High-Performance Quantitation and Identification The industry-standard API 4000 LC/MS/MS System brings highperformance quantitation and identification to every phase of pharmaceutical development from drug discovery to clinical trials. The system s superior sensitivity also ensures low detection limits for trace analysis of pesticide/drug residues in food and environmental samples, forensic toxicology and clinical research applications. Integrated with powerful Analyst software, the system provides faster access to information for DMPK in drug development. The API 4000 system includes: Innovative Turbo V ion source for efficient ionization and high sensitivity quantitation over a wide range of flow rates LINAC collision cell technology for faster scan times Curtain Gas interface for reduced maintenance and maximum productivity Enhanced high flow-rate performance, reduced ionization suppression, self-cleaning probe design and reliable interface for high-throughput productivity Optional DuoSpray ion source for fast method development and increased throughput Optional PhotoSpray source expands the range of compounds for analysis Industry-standard Windows-based Analyst software with tools for GLP compliance, including 21 CFR Part 11 Optional NanoSpray source for improved sensitivity at lowest flow rates The API 5000 LC/MS/MS System The Most Sensitive Triple Quad for Complex Bioanalytical Samples The API 5000 LC/MS/MS system offers a wide linear dynamic range and exceptional sensitivity for routine quantitation of low abundance compounds in complex matrices, with greater signal-to-noise than the industry-standard API 4000 system. It also provides unequalled accuracy and precision for quantitative analysis of small molecules. Designed to deliver the lowest detection limits for the most demanding DMPK and ADMET studies, the API 5000 system combines new QJet ion guide technology with the proven Turbo V ion source and a powerful new generation of Analyst software. The result is a robust, high-throughput platform for every phase of pharmaceutical development and a new level of quantitative performance. This reliable, easy-to-use system includes: Revolutionary new QJet ion guide dramatically improves sensitivity by efficiently capturing and focusing more ions into the mass analyser Patented LINAC collision cell ensures maximum ion transfer (free of cross-talk) in MS/MS mode for simultaneous multi-compound analysis, monitoring and MRM Proprietary Curtain Gas interface for reduced maintenance and maximum productivity Turbo V ion source for enhanced high flow-rate performance, reduced ionization suppression, self-cleaning probe and interface reliability Optional DuoSpray ion source for fast method development and increased throughput Optional PhotoSpray source for expanded compound analysis range

HYBRID SYSTEMS The 3200 Q TRAP LC/MS/MS System Triple Quad and Linear Ion Trap Technology Combined in a Single Platform The 3200 Q TRAP LC/MS/MS system uses patented technology to create a high performance Hybrid Triple Quadrupole Linear Ion Trap. By combining the specificity and robustness of a triple quadrupole with the full scan MS/MS sensitivity of a linear ion trap, this unique technology enables you to characterize and quantify a wider range of small molecules and drug metabolites on a single system. Triple quadrupole performance delivers qualitative and quantitative LC/MS/MS (true precursor ion scan, neutral loss scan, MRM and wide linear dynamic range) Hybrid linear ion trap performance delivers structural identification or confirmation (MS 2, MS 3, enhanced resolution, high sensitivity full scan) Analyst software provides innovative qualitative analysis tools, including spectrum library and fragment interpretation The 4000 Q TRAP LC/MS/MS System An Innovation in Hybrid Triple Quadrupole Linear Ion Trap Technology The 4000 Q TRAP LC/MS/MS System provides high-sensitivity quantitative and qualitative capabilities in one instrument. The ability to combine triple quadrupole scan types with linear ion trap scan types makes this the ideal system for applications requiring rapid, automated quantitative and qualitative analysis at lowest concentration levels such as drug discovery, ADME/Tox, metabolomics, pharmacokinetics, forensics, clinical research, environmental and food trace analysis. This powerful system provides: High-sensitivity full-scan MS, CID-MS/MS, and MS 3 with high-selectivity from true triple quadrupole MRM, precursor ion (PI) and neutral loss (NL) scans Hybrid Linear Ion Trap technology with a triple quadrupole collision cell to produce library searchable MS/MS spectra, with reduced cycle times and without low mass cut-off MS 3 data for structural elucidation Analyst software provides innovative qualitative analysis tools, including spectrum library and fragment interpretation Skimmer Q0 High pressure Cell ST Q1 Q2 LINAC Collision Cell Q3 EXB DF Orifice IQ2 IQ3 C2B DET Curtain Gas Interface

SOFTWARE AND SERVICE The QSTAR Elite Hybrid LC/MS/MS System Enhanced QqTOF Technology for Faster Metabolite Discovery, Identification and Structural Elucidation The QSTAR Elite system takes QqTOF performance to a new level by providing greater sensitivity, higher mass resolution, increased mass accuracy, faster MS/MS, and increased linear dynamic range. Along with improved workflows and more intelligent data acquisition, these performance enhancements help to ensure that you get more meaningful information from every experiment. Multiple ion sources extend flexibility across a wide range of applications Increased dynamic range up to four orders of magnitude in full scan mode without signal reduction for optimized quantitation Analyst Software in the Validated Environment Designed with complete set of features necessary for GLP and 21 CFR Part 11 Regulations. Provides tools for multi-instrument, project-wide security from a single computer Offers configurable audit map functionality, preventing redundant or unnecessary event capture Improved Network Acquisition Capabilities allow for better data storage and data backup Role-based Architecture allows labs to customize Analyst Software to their lab environment Enhanced Validation Package proposes a full set of validation materials for software upgrades New Razor detector for improved resolution and mass accuracy Powerful, application-specific software tools provide you with efficient system control, data collection and analysis Remote Instrument Monitoring 1 New turbo pump design runs cooler for enhanced reliability 2 New LINAC II collision enables faster MS to MS/MS switching 3 Optional IonCooler Guide allows collisional coding of large noncovalently-bound complexes, significantly increasing the sensitivity for the complexes of 0.5 MDa and above. Maximize instrument uptime with Applied Biosystems Smart Monitoring Service. With Smart Monitoring, we can remotely and proactively track critical system parameters over the Internet and identify potential instrument problems before they affect your lab s efficiency. Using a combination of remote preemptive monitoring and remote diagnostics, many of our customers are experiencing a significant increase in instrument uptime.

Applied Biosystems/MDS SCIEX Systems are Used in a Wide Variety of Applications Drug Discovery and Development Applied Biosystems/MDS SCIEX LC/MS/MS systems play a key role in drug discovery and development. Improved ionization and interface technologies together with powerful software capabilities provide pharmaceutical researchers with unprecedented performance for applications ranging from target discovery to manufacturing quality control. Automated metabolite identification and characterization ADME Studies Drug target screening Impurity profiling Pharmacokinetic studies Metabolomics Tissue imaging Drug Development Quantitative Analysis of Buspirone Metabolites using LC/MS/MS Early assessment of drug metabolism of in vitro and in vivo samples requires sufficient sensitivity and specificity to measure nanogram levels of metabolites in complex matrices. The API 5000 LC/MS/MS system gives you unequalled accuracy and precision for quantitative analysis of small molecules. It also offers linearity over a wide dynamic range and exceptional sensitivity for routine quantitation of low abundance compounds in complex matrices. Drug Discovery Determination of Phase I Metabolites of Glyburide Using the 4000 Q TRAP System, A Hybrid Triple Quadrupole/Linear Ion Trap Mass Spectrometer A common strategy for metabolite MS analysis consists of using a triple quadrupole precursor and neutral loss analysis in conjunction with an ion trap single MS 1 survey with MS 2 and MSn dependent scans. Triple quadrupole scan modes provide a very selective method for the identification of structurally similar metabolites, even in the presence of strong co-eluting signals. The superior sensitivity of 4000 Q TRAP System makes it possible to detect ultra-low level metabolites, and a large number of unique metabolites can be found using the system s various scan modes. This combination provides a comprehensive view of the metabolites of glyburide. 367.1 168.8 x 100.0 393.1 2300 385.0 286.0 369.0 269.3 115.9 411.1 227.9 508.0 302.2 142.0 526.3 199.1 490.2 312.0 402.8 464.2 154.9 276.1 341.4 569.9 119.9 424.2 100 150 200 250 300 350 400 450 500 550 600 m/z, amu cps 20 22 24 26 28 30 32 Time, min 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 38 40 Time, min Excellent linearity over a wide dynamic range is illustrated in this calibration curve of eight replicate injections at each concentration of buspirone. From the table, the statistics and accuracy demonstrate unparalleled consistency and reproducibility required for quantitation in regulated environments. MRM-triggered IDA survey detecting oxidized metabolite.

Metabolomics Studies Metabolomics Analysis of Rat Urine Before and After Administration of Vinpocetine In this study, MarkerView Software is used in the analysis of the effects of vinpocetine, a compound derived from vincamine, a constituent found in the leaves of common Periwinkle plant, Vinca minor L. Vinpocetine is believed to improve cerebral metabolism (glucose and oxygen uptake), increase ATP concentration, and selectively increase blood flow to the brain. After dosing rats with Vinpocetine, urine samples were collected at several different time points, monitoring the alteration in endogenous as well as xenobiotic metabolites as a result of drug administration. Metabolite Identification Identification of Propranolol Metabolites from Human Urine Samples Using the QSTAR Elite System In a drug metabolism research study, the goal is to identify all of the metabolites, both major and minor. This can be a challenging task on an LC time-scale, especially because the ions of interest may not be the most intense ions in the mass spectrum. Automated LC/MS/MS workflows using Information Dependent Acquisition (IDA) provide the framework for deriving maximum information from every LC experiment. The IDA functionality lets you focus on specific ions of interest for increased productivity. Several tools are available to narrow the search, but significant improvements have been made with the implementation of Dynamic Background Subtraction (DBS) and Mass Defect triggered IDA Software (MDt IDA Software) on the QSTAR Elite system. To highlight the power of this combination, the QSTAR Elite system was used to identify the metabolites of propanolol from human urine samples. Experiments were run to compare the number of metabolites found using a standard IDA run (dynamic exclusion) versus a combination of Dynamic Background Subtraction (DBS) and MDt IDA Software features, as compared to the expected metabolites based on the literature. Standard IDA w/ DBS w/ DBS & MDt IDA # of ions selected 912 496 288 # of Metabolites ID d 10 27 27 Results of PCA analysis on the positive electrospray Vinpocetine data. Comparison of automated data collection for metabolites of propranolol. The combination of DBS and MDt IDA significantly improves the overall efficiency of automated workflows. By greatly narrowing the search higher quality, more relevant data is collected yielding improved metabolite coverage and additional time for more experiments.

Clinical Research Applied Biosystems/MDS SCIEX LC/MS/MS systems offer analytical power, proven applications, and ease-of-use for clinical research. Therapeutic Drug Efficacy Inborn Errors of Metabolism Endocrinology Research Biomarkers Toxicology Forensics and Toxicology Applied Biosystems/MDS SCIEX LC/MS/MS systems offer unparalleled performance for identifying analytes in complex samples. Provides the maximum amount Impurity profiling of information from one LC run, Enables structural confirmation both qualitative and quantitative of drug compounds with General unknown/targeted compound libraries screening for xenobiotics in Doping analysis blood, urine and saliva samples Clinical Research A Simple and Rapid LC/MS/MS Method for the Simultaneous Determination of 4 Immunosuppressant Drugs Liquid chromatography in combination with tandem mass spectrometry has the potential for the simultaneous determination of Cyclosporin A, Tacrolimus, Sirolimus, and Everolimus with greater specificity, lower detection limits, and a broader dynamic range than commercial immunoassays. The LC/MS/MS method allows the effective removal of high-molecular compounds, important for the long-term robustness of the method, as well as minimal sample handling and rapid sample turn-around time. The concentration and identification of these immunosuppressant drugs in research studies can thus be accomplished quickly and simply, with minimal manual sample clean-up and without compromising assay precision and accuracy. Forensic Toxicology Simultaneous Qualitative and Quantitative LC/MS/MS Analysis of Opiates in Biological Matrices Although ELISA and immunoassays are sensitive techniques for detecting opiates, there is a high degree of false-positive results due to cross-reactivities among related opiates. Identification of these illicit drugs for forensic, clinical or drug-testing applications requires a specific and sensitive method. LC/MS/MS offers a simultaneous qualitative and quantitative method for analyzing opiates in biological matrices. With the advent of the hybrid quadrupole/ion trap Q TRAP System, LC/MS/MS techniques can reliably detect these compounds without any additional sample preparation or instrument time. Simultaneous determination of four immunosuppressant drugs in 100 µl of blood using an Applied Biosystems/MDS Sciex LC/MS/MS system. The total run time was 2.5 minutes. Analysis of Morphine and its metabolites using targeted MRM with Product Ion Scan in Urine Applied Biosystems products are for research use only. Not for use in diagnostic procedures.

Food and Environmental Applied Biosystems/MDS SCIEX LC/MS/MS systems enable laboratories to characterize and monitor a wide range of compounds simultaneously, with minimal sample clean up and fast analysis times. Multi-target compound analysis Residue/contaminant screening Unknown screening and confirmation Qualitative and quantitative analysis of a wide variety of compound classes including: - Antibiotics - Mycotoxins - Beta Agonists - Acrylamide - Pesticides Food Environmental Detection of Nitrofurane Metabolites in Food with LC/MS/MS Furazolidone, furaltadone, nitrofurazone and nitrofurantoine belong to the group of nitrofuranes once used as antibiotics for treatment of gastrointestinal infections in cattle and poultry. Due to their proven mutagenic and carcinigenic effect, nitrofuranes (except for furazolidone) were prohibited in 1993 in the European Union. Despite their low molecular weight, the derivatized metabolites can be quantitated over several orders of magnitude with high accuracy using methods developed on Applied Biosystems/MDS SCIEX triple quadrupole LC/MS/MS systems. Simultaneous Quantitative Screening and Qualitative Confirmation of 300 Pesticides Using the 3200 Q TRAP LC/MS/MS System Contamination of natural waters with pesticides from agriculture is a problem of primary concern. Many pesticides which are difficult or impossible to analyze by GC/MS can be identified and quantified by LC/MS/MS after simple solvent extraction and fast cleanup. The 3200 Q TRAP System uses the acquisition time mainly for fast screening of as many target compounds as possible. Automatic confirmatory measurements are then only carried out when a pesticide is detected. The confirmatory measurement provides full collision induced mass spectra, which can be searched against a mass spectral library of pesticides. Typical detection limits: API 4000 LC/MS/MS System: meat extract with 0.2 µg/kg AOZ. 2-NBA-AOZ: 236/134 (blue), 236/192 (red): standard with 0.2 µg/l 2-NBA-AOZ (236/134) (grey). Screening for pesticides in water and food samples: A: MRM transitions of 300 targeted pesticides B: MRM of 10 µg/l Atrazine C: Enhanced Product Ion Spectrum to search against a mass spectral library (3200 Q TRAP LC/MS/MS System)

Make The Choice for Optimum Performance LC/MS is a powerful analytical technology that offers substantial benefits. There are four basic components that make up a Mass Spectrometry instrument. Applied Biosystems/MDS SCIEX has worked at the forefront of the industry to innovate and develop the most advanced technological solutions in each of these components in order to deliver the most powerful systems available to our customers. To assist you in maintaining the highest levels of instrument up-time and performance, Applied Biosystems offers performance agreements with several levels of coverage from regular planned maintenance visits and service calls to total system protection. Your Applied Biosystems representative can provide you with complete information on available programs. Choose the plan that best meets your service needs. For Research Use Only. Not for use in diagnostic procedures. Applera Corporation is committed to providing the world s leading technology and information for life scientists. Applera Corporation consists of the Applied Biosystems and Celera Genomics businesses. Applied Biosystems and AB (design) are registered trademarks and Applera is a trademark of Applera Corporation or its subsidiaries in the US and/or certain other countries. Analyst, QSTAR, Q TRAP, LINAC, PhotoSpray, NanoSpray, MicroIonSpray and TurbolonSpray are registered trademarks and API 2000, API 3000, API 3200, API 4000, API 5000, MarkerView, Curtain Gas, DuoSpray, IonSpray, Razor, IonCooler, MDt, QJet and Turbo V are trademarks of Applied Biosystems/MDS SCIEX, which is a joint venture between Applera Corporation and MDS Inc. 2006 Applera Corporation and MDS Inc. All rights reserved. Printed in the USA, 04/2007 Publication 114BR20-02. Headquarters 850 Lincoln Centre Drive Foster City, CA 94404 USA Phone 650.638.5800 Toll Free 800.345.5224 www.appliedbiosystems.com International Sales For our office locations please call the division headquarters or refer to our Web site at www.appliedbiosystems.com/about/offices.cfm