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2.6 Million Users Can’t Be Wrong*

Nicholas Duczak
Keeley Murphy



*Slides courtesy of Patrick Bennett (in other words, blame him)
*Marketing survey of blackberry users considering switching to
iPhone 5
Marketing Surveys




2
Still have a Blackberry?




3
Did you have one a year ago? Two?
Thirteen?




4
New Technology, Same Old Game




5
Innovation…circa 1999
                                                              13 years ago….The TSQ 7000!
                                                             TSQ® 7000
                                                             Triple-Stage Quadrupole Mass Spectrometer
                                                             The TSQ 7000 is the next generation in triple-stage
                                                             quadrupole technology, the most advanced, versatile, and
                                                             powerful mass spectrometer available in its class.
                                                             The 7000 Series features new, longer quadrupoles for
                                                             improved resolution, a non-linear octapole collision cell
                                                             providing efficient collision-induced dissociation (CID) and
                                                             neutral noise reduction, an advanced 15 kV conversion
                                                             dynode detector to enhance sensitivity, and digital signal
                                                             processing for improved detection limits.
                                                             The TSQ also offers the most complete range of sample
                                                             introduction techniques available for unequaled versatility.
                                                             Advanced MS/MS capabilities enable you to solve virtually
                                                             any analytical problem today, and into the future.


Data System
Software
•Instrument Control Language'" with GUIDE" step‑by-step control and ICIS"11 applications software— mouse driven or keyboard
control, multi-window‑ing environment with Motir graphical user interface


Performance Specifications
LC/MS Sensitivity
…A loop injection of 5µL of a 10 pg µL -1 solution of reserpine [50 picograms total sample]



 6
Innovation…2012




7
Formoterol extract (10 pg/mL, MRM w/ 1D Chromatography)




                                   30uL injection




8
Formoterol extract (1 pg/mL, Q Exactive w/ 1D Chromatography)
       RT: 0.00 - 2.01
                                                             RT: 0.95                                   NL: 4.14E3
                                                             AA: 15655                                  m/z= 149.09549-149.09699 F:
                             100
                                                                                                        FTMS + p ESI Full ms2
                                                                                                        345.18@hcd35.00
                              90
                                                                                                        [75.00-370.00] MS ICIS
                                                                                                        Formoterol-Vial-
                              80                                                                        13_120607100045
                              70
        Relative Abundance




                              60                                             0.1 pg/mL on column (10uL)
                              50

                              40

                              30

                              20

                              10

                              0
                                                             RT: 0.97                                   NL: 1.31E5
                                                             AA: 558147                                 m/z= 155.13299-155.13455 F:
                             100
                                                                                                        FTMS + p ESI Full ms2
                                                                                                        351.22@hcd35.00
                              90
                                                                                                        [75.00-375.00] MS ICIS
                                                                                                        Formoterol-Vial-
                              80                                                                        13_120607100045
                              70
        Relative Abundance




                              60

                              50

                              40

                              30

                              20

                              10

                              0
                               0.0   0.2   0.4   0.6   0.8         1.0        1.2   1.4   1.6   1.8   2.0
                                                                Time (min)




9
ASMS – Q Exactive Pharma/Biopharma

     • Oral: WOC pm - Regulated Bioanalysis using High Resolution LC/MS:
       Headache or Opportunity?
        •Quantitative Pharmacokinetic Sample Analysis and Metabolite Identification of Buspirone
      using High Resolution Accurate Mass Spectrometry, Kevin Cook1; Rose Herbold1; Keeley
      Murphy 1; Panos Hatsis 2, 1Thermo Fisher Scientific, San Jose, CA; 2Novartis, Cambridge, MA
       •Evaluation of Resolving Power and Extraction Window with Comparison of Profile and
      Centroid Modes for High-Resolution Mass Spectrometry Phospholipid Quantitation, Mingkun
      Fu ; Qing Lu, Millennium: the Takeda Oncology Company, Cambridge, MA


     • Oral: MOC pm - Integrated Qualitative and Quantitative LC-MS for Small
       Molecule Analysis
        •Development of a Higher Throughput Metabolite Screening Assay in Early ADME Profiling
      Using Generic HRMS Acquisition and Automated Data Processing, Anthony Paiva1; Cheryl
      Klakouski1; Tatyana Zvyaga1; Dieter Drexler1; Jonathan Josephs 1; Harold Weller1; Wilson
      Shou 1; Ismael Zamora2, 1Bristol-Myers Squibb Company, Wallingford, CT; 2Lead Molecular
      Design, San Cugat del Valles, Spain




10
ASMS – Q Exactive Pharma/Biopharma
     • Drug discovery PK analysis using a quadrupole high resolution orbitrap
       mass spectrometer (Q Exactive): an alternative approach to triple
       quadrupole , Hongying Gao; Andre Negahban, Pfizer, Inc, Groton, CT
     • The Opening of Bioanalytical Space Through Benchtop Accurate Mass
       Spectrometry: The Analysis of Propofol and its Four Metabolites, Beijing
       Tan1; Yizhong Zhang2; Andre Negahban3; Hongying Gao4; Christopher
       Holliman5, 1Pfizer, Inc., Groton, CT; 2Pfizer Inc., Groton, CT; 3Pfizer,
       Groton, CT; 4Pfizer, Inc, Groton, CT; 5Pfizer Inc, Groton, CT
     • High Throughput Bioanalysis of Bile Acids and Bile Salts Using UHPLC
       Coupled with High Resolution Mass Spectrometers (HR-MS), Jie Ding;
       Eric Lund; Donald Mckenzie; John Lindsay, Covance Laboratories Inc.,
       Madison, WI
     • Utility of High-Resolution-Accurate-Mass to Minimize Interference in
       Simultaneous Determination of Ribavirin and its Phosphate Metabolites in
       an In Vitro Assay, Cong Wei; James E. Grace Jr.; Tatyana Zvyaga; Dieter
       M. Drexler, Bristol-Myers Squibb Company, Research&Development,
       Wallingford, CT
11
ASMS – Q Exactive Pharma/Biopharma
     • Utilizing a Non-Targeted HR/AM-MS Method to Accelerate Quantitative
       Throughput for In-Vitro Metabolic Profiling, Keeley Murphy ; Kevin Cook;
       Tim Stratton; Patrick Bennett, Thermo Fisher Scientific, San Jose, CA
     • Ultra High-throughput MS Methods for the Discovery of Histone
       Demethylase Inhibitors, John M. Peltier1; Nicole White1; Priti Gaitonde1;
       Wendy Broom1; Zhao Bin Kang1; Ji-Hu Zhang1; Michael Acker1; Keeley
       Murphy2; David Farley1; W. Adam Hill1, 1Novartis Institutes for Biomedical
       Research, Cambridge, MA; 2Thermo-Fisher Scientific, San Jose, US
     • Quantitation of Oligonucleotides In Human Plasma Using Q-Exactive
       Orbitrap High Resolution MS, Weiwei Yuan1; Laixin Wang1; Min Meng1;
       Jessica Wang2; Kevin Cook 2; Patrick Bennett2, 1Tandem Labs, Salt Lake
       City, UT; 2Thermo Fisher Scientific, San Jose, CA
     • Robust Ultra High Sensitivity Quantitative Analysis using Low Flow
       LC/MS/MS and Reduced Phospholipid Matrix Effects. Myth or Reality?,
       David Humphries1; Roger N. Hayes1; Kevin Cook2; Mark Dreyer2; Xiang
       He2; Subodh Nimkar2; Patrick Bennett2, 1MPI Research, Mattawan,
       MI; 2Thermo Fisher Scientific, San Jose, CA
12
ASMS – Q Exactive Pharma/Biopharma
     • Evaluation of Resolution/Scan Speed Limitations for Quantitation of Small
       Molecules by UHPLC-HRMS on the Q-Exactive Platform, Allysen
       Meymaris1; Richard Lelacheur1; Patrick Bennett2; Kevin Cook2; Xin Zhang1,
       1
        Agilux Labs, Worcester, MA; 2Thermo Fisher, San Jose, CA
     • Quantification of Plant Expressed Proteins Using High Resolution LC/MS,
       Jeffrey Gilbert; Trent Oman; Debbie Schwedler; John Lawry; Jesse
       Balcer; Suresh Babu Annangudi Palani; Yelena A. Adelfinskaya; Brian
       Wendelburg; Barry Schafer, Dow AgroSciences, Indianapolis, IN
     • Quantitative Bioanalysis using the Q Exactive HRMS: Factors in
       choosing Resolution and Scan Type, Jack Cunniff1; Chris Yang2; Yujin
       Wang2; Kevin Cook1; Patrick Bennett1, 1Thermo Fisher Scientific, San
       Jose, CA; 2Gilead Sciences, Foster City, CA
     • Improving the Bioanalysis of Endogenous Bile Acids as Biomarkers for
       Hepatobiliary Toxicity, Troy Voelker1; Kevin Cook2; Min Meng 1; Patrick
       Bennett2, 1Tandem Labs, Salt Lake City, UT; 2Thermo Fisher Scientific,
       San Jose, CA


13
ASMS – Q Exactive Pharma/Biopharma
     • UHPLC-ESI-HRMS quantitation of metabolites without using reference
       standards-Impact of mobile phase composition on MS respons, Sumithra
       Katragadda; Dil Ramanthan, Kean University, Iselin, NJ
     • LC/SRM Has Come of Age to Quantitate Proteins: Amyloid β isoforms
       measured in Human Cerebrospinal Fluid and Compared to ELISA, Kwasi
       Mawuenyega; Tom Kasten; Vitaliy Ovod; Kelly Moor; Ling Munsell; Rose
       Connors; Wendy Sigurdson; Randall Bateman, Washington University
       School of Medicine, Saint Louis, MO
     • Quantitation of Melatonin and N-Acetylserotonin in Human Plasma by
       Nanoflow LC-MS/MS and Electrospray LC-MS/MS, Melissa D. Carter; M.
       Wade Calcutt; Beth A. Malow; Kristie Lindsey Rose; David L. Hachey,
       Vanderbilt University, Nashville, TN




14
Innovation- circa 2025

                          • Learn more about HR/AM and
                            Q Exactive.

                          • Visit the site at
                            http://www.planetorbitrap.com




15
Attend the Thermo Users Meetings




16
Attend the Thermo Users Meetings




17
…we seem to be having some technical
 difficulties…please stay on the line….




18

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12 2.6 million users can't be wrong keeley murphy and nick duczak - thermo scientific

  • 1. 2.6 Million Users Can’t Be Wrong* Nicholas Duczak Keeley Murphy *Slides courtesy of Patrick Bennett (in other words, blame him) *Marketing survey of blackberry users considering switching to iPhone 5
  • 3. Still have a Blackberry? 3
  • 4. Did you have one a year ago? Two? Thirteen? 4
  • 5. New Technology, Same Old Game 5
  • 6. Innovation…circa 1999 13 years ago….The TSQ 7000! TSQ® 7000 Triple-Stage Quadrupole Mass Spectrometer The TSQ 7000 is the next generation in triple-stage quadrupole technology, the most advanced, versatile, and powerful mass spectrometer available in its class. The 7000 Series features new, longer quadrupoles for improved resolution, a non-linear octapole collision cell providing efficient collision-induced dissociation (CID) and neutral noise reduction, an advanced 15 kV conversion dynode detector to enhance sensitivity, and digital signal processing for improved detection limits. The TSQ also offers the most complete range of sample introduction techniques available for unequaled versatility. Advanced MS/MS capabilities enable you to solve virtually any analytical problem today, and into the future. Data System Software •Instrument Control Language'" with GUIDE" step‑by-step control and ICIS"11 applications software— mouse driven or keyboard control, multi-window‑ing environment with Motir graphical user interface Performance Specifications LC/MS Sensitivity …A loop injection of 5µL of a 10 pg µL -1 solution of reserpine [50 picograms total sample] 6
  • 8. Formoterol extract (10 pg/mL, MRM w/ 1D Chromatography) 30uL injection 8
  • 9. Formoterol extract (1 pg/mL, Q Exactive w/ 1D Chromatography) RT: 0.00 - 2.01 RT: 0.95 NL: 4.14E3 AA: 15655 m/z= 149.09549-149.09699 F: 100 FTMS + p ESI Full ms2 345.18@hcd35.00 90 [75.00-370.00] MS ICIS Formoterol-Vial- 80 13_120607100045 70 Relative Abundance 60 0.1 pg/mL on column (10uL) 50 40 30 20 10 0 RT: 0.97 NL: 1.31E5 AA: 558147 m/z= 155.13299-155.13455 F: 100 FTMS + p ESI Full ms2 351.22@hcd35.00 90 [75.00-375.00] MS ICIS Formoterol-Vial- 80 13_120607100045 70 Relative Abundance 60 50 40 30 20 10 0 0.0 0.2 0.4 0.6 0.8 1.0 1.2 1.4 1.6 1.8 2.0 Time (min) 9
  • 10. ASMS – Q Exactive Pharma/Biopharma • Oral: WOC pm - Regulated Bioanalysis using High Resolution LC/MS: Headache or Opportunity? •Quantitative Pharmacokinetic Sample Analysis and Metabolite Identification of Buspirone using High Resolution Accurate Mass Spectrometry, Kevin Cook1; Rose Herbold1; Keeley Murphy 1; Panos Hatsis 2, 1Thermo Fisher Scientific, San Jose, CA; 2Novartis, Cambridge, MA •Evaluation of Resolving Power and Extraction Window with Comparison of Profile and Centroid Modes for High-Resolution Mass Spectrometry Phospholipid Quantitation, Mingkun Fu ; Qing Lu, Millennium: the Takeda Oncology Company, Cambridge, MA • Oral: MOC pm - Integrated Qualitative and Quantitative LC-MS for Small Molecule Analysis •Development of a Higher Throughput Metabolite Screening Assay in Early ADME Profiling Using Generic HRMS Acquisition and Automated Data Processing, Anthony Paiva1; Cheryl Klakouski1; Tatyana Zvyaga1; Dieter Drexler1; Jonathan Josephs 1; Harold Weller1; Wilson Shou 1; Ismael Zamora2, 1Bristol-Myers Squibb Company, Wallingford, CT; 2Lead Molecular Design, San Cugat del Valles, Spain 10
  • 11. ASMS – Q Exactive Pharma/Biopharma • Drug discovery PK analysis using a quadrupole high resolution orbitrap mass spectrometer (Q Exactive): an alternative approach to triple quadrupole , Hongying Gao; Andre Negahban, Pfizer, Inc, Groton, CT • The Opening of Bioanalytical Space Through Benchtop Accurate Mass Spectrometry: The Analysis of Propofol and its Four Metabolites, Beijing Tan1; Yizhong Zhang2; Andre Negahban3; Hongying Gao4; Christopher Holliman5, 1Pfizer, Inc., Groton, CT; 2Pfizer Inc., Groton, CT; 3Pfizer, Groton, CT; 4Pfizer, Inc, Groton, CT; 5Pfizer Inc, Groton, CT • High Throughput Bioanalysis of Bile Acids and Bile Salts Using UHPLC Coupled with High Resolution Mass Spectrometers (HR-MS), Jie Ding; Eric Lund; Donald Mckenzie; John Lindsay, Covance Laboratories Inc., Madison, WI • Utility of High-Resolution-Accurate-Mass to Minimize Interference in Simultaneous Determination of Ribavirin and its Phosphate Metabolites in an In Vitro Assay, Cong Wei; James E. Grace Jr.; Tatyana Zvyaga; Dieter M. Drexler, Bristol-Myers Squibb Company, Research&Development, Wallingford, CT 11
  • 12. ASMS – Q Exactive Pharma/Biopharma • Utilizing a Non-Targeted HR/AM-MS Method to Accelerate Quantitative Throughput for In-Vitro Metabolic Profiling, Keeley Murphy ; Kevin Cook; Tim Stratton; Patrick Bennett, Thermo Fisher Scientific, San Jose, CA • Ultra High-throughput MS Methods for the Discovery of Histone Demethylase Inhibitors, John M. Peltier1; Nicole White1; Priti Gaitonde1; Wendy Broom1; Zhao Bin Kang1; Ji-Hu Zhang1; Michael Acker1; Keeley Murphy2; David Farley1; W. Adam Hill1, 1Novartis Institutes for Biomedical Research, Cambridge, MA; 2Thermo-Fisher Scientific, San Jose, US • Quantitation of Oligonucleotides In Human Plasma Using Q-Exactive Orbitrap High Resolution MS, Weiwei Yuan1; Laixin Wang1; Min Meng1; Jessica Wang2; Kevin Cook 2; Patrick Bennett2, 1Tandem Labs, Salt Lake City, UT; 2Thermo Fisher Scientific, San Jose, CA • Robust Ultra High Sensitivity Quantitative Analysis using Low Flow LC/MS/MS and Reduced Phospholipid Matrix Effects. Myth or Reality?, David Humphries1; Roger N. Hayes1; Kevin Cook2; Mark Dreyer2; Xiang He2; Subodh Nimkar2; Patrick Bennett2, 1MPI Research, Mattawan, MI; 2Thermo Fisher Scientific, San Jose, CA 12
  • 13. ASMS – Q Exactive Pharma/Biopharma • Evaluation of Resolution/Scan Speed Limitations for Quantitation of Small Molecules by UHPLC-HRMS on the Q-Exactive Platform, Allysen Meymaris1; Richard Lelacheur1; Patrick Bennett2; Kevin Cook2; Xin Zhang1, 1 Agilux Labs, Worcester, MA; 2Thermo Fisher, San Jose, CA • Quantification of Plant Expressed Proteins Using High Resolution LC/MS, Jeffrey Gilbert; Trent Oman; Debbie Schwedler; John Lawry; Jesse Balcer; Suresh Babu Annangudi Palani; Yelena A. Adelfinskaya; Brian Wendelburg; Barry Schafer, Dow AgroSciences, Indianapolis, IN • Quantitative Bioanalysis using the Q Exactive HRMS: Factors in choosing Resolution and Scan Type, Jack Cunniff1; Chris Yang2; Yujin Wang2; Kevin Cook1; Patrick Bennett1, 1Thermo Fisher Scientific, San Jose, CA; 2Gilead Sciences, Foster City, CA • Improving the Bioanalysis of Endogenous Bile Acids as Biomarkers for Hepatobiliary Toxicity, Troy Voelker1; Kevin Cook2; Min Meng 1; Patrick Bennett2, 1Tandem Labs, Salt Lake City, UT; 2Thermo Fisher Scientific, San Jose, CA 13
  • 14. ASMS – Q Exactive Pharma/Biopharma • UHPLC-ESI-HRMS quantitation of metabolites without using reference standards-Impact of mobile phase composition on MS respons, Sumithra Katragadda; Dil Ramanthan, Kean University, Iselin, NJ • LC/SRM Has Come of Age to Quantitate Proteins: Amyloid β isoforms measured in Human Cerebrospinal Fluid and Compared to ELISA, Kwasi Mawuenyega; Tom Kasten; Vitaliy Ovod; Kelly Moor; Ling Munsell; Rose Connors; Wendy Sigurdson; Randall Bateman, Washington University School of Medicine, Saint Louis, MO • Quantitation of Melatonin and N-Acetylserotonin in Human Plasma by Nanoflow LC-MS/MS and Electrospray LC-MS/MS, Melissa D. Carter; M. Wade Calcutt; Beth A. Malow; Kristie Lindsey Rose; David L. Hachey, Vanderbilt University, Nashville, TN 14
  • 15. Innovation- circa 2025 • Learn more about HR/AM and Q Exactive. • Visit the site at http://www.planetorbitrap.com 15
  • 16. Attend the Thermo Users Meetings 16
  • 17. Attend the Thermo Users Meetings 17
  • 18. …we seem to be having some technical difficulties…please stay on the line…. 18

Editor's Notes

  1. Method is L/L extraction followed by SPE extraction, then LC/LC heart cut – so, 2D chrom. Above is 1D chrom on API5000. 0.5 mL extract, recon in 100, inject 30. QE was only 1D, inject 5 uL.