Older Events
May 6, 2014 – MSDG Meeting
The NJ Mass Spectrometry Discussion Group presents its May Meeting on Tuesday, May 6, 2014 at at the Holiday Inn Somerset-Bridgewater, 195 Davidson Ave, Somerset NJ 08873
Sponsored by Waters
Attendance is free of charge, compliments of our sponsors!
Please register here.
Featured Speakers:
I. James Settlage Ph.D.
Inventiv Health Clinical, Princeton, NJ
“Leveraging the power of Supercritical Fluid Chromatography coupled with Triple Quadrupole Mass Spectrometry to meet otherwise intractable bioanalytical challenges”
II. Gene Ciccimaro, Ph.D.
Bristol-Myers Squibb, Lawrenceville, NJ
“Meeting the Needs of Biopharma Drug Discovery by Increasing Sensitivity Using ionKey Technology and Protein Immunoenrichment Cleanup”
Program
5:30 pm – Social and registration
6:15 pm – Complimentary dinner
7:00 pm – Welcome and opening remarks
7:05 pm – Dr. Settlage
8:00 pm – Dr Ciccimaro
8:55 pm – Closing remarks
Abstract for Talk II:
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Current challenges facing the Discovery Bioanalyst include the need to understand the biology of preclinical disease models and demonstrate on target effects. Perturbations of biomarkers, protein ligands and receptors need to be quantified in both circulation and in tissues from target organs. Bioanalytical assays to provide this data require exquisite sensitivity due not only to extremely low endogenous levels, but also limited sample volume. To overcome these demands, we attempt to incorporate sample cleanup using immunoenrichment followed by low flow LC-MS technology using the ionKey micro column tile emitter and TQS mass spectrometer. There is a known asymptotic increase in analyte ESI-MS signal response with reduced solvent flow rate. Considering optimal QqQ instrumental ion transfer efficiency loss, a reduction from traditional flow rate (400-800 µL/min) to low micro-flow rates (1-5 µL/min) will on average result in 10-30X, and a reduction to nano-flow rate (<1 µL/ min) will result in ~ 50X gain in signal intensity. These intensity gains however, do not directly correlate to gains in analytical assay sensitivity (reduced LLOQ). In this study we highlight this disconnect when porting a protein immunoenrichment method from traditional to micro-flow LC-MS/MS. We identify charge competition as the cause for the performance gap, and show results from an improved sample preparation that achieves improved assay performance by maximizing sample loading and minimizing charge saturation. We highlight the use of this technology to support drug discovery efforts.
Authors: Bogdan Sleczka, Eugene Ciccimaro, John Mehl, Lorell Discenza, Asoka Ranasinghe, Celia D’Arienzo, Timothy Olah (Bristol-Myers Squibb, Lawrenceville, NJ). Catalin Doneau, Brad Coopersmith, Jim Murphy (Waters)
(Past Events)
Apr 8, 2014 – MSDG Meeting
The NJ Mass Spectrometry Discussion Group presents its April Meeting on Tuesday, Apr 8, 2014 at at the Holiday Inn Somerset-Bridgewater, 195 Davidson Ave, Somerset NJ 08873
Sponsored by Agilent Technologies
Attendance is free of charge, compliments of our sponsors!
Please register here.
Featured Speakers:
I. Daina Avizonis
PhD, Manager / Research Associate, Metabolomics Core Facility,
McGill University, Goodman Cancer Center
“Fueling Cancer: Using Metabolomics to Study Cancer Biology”
II. Jim Lau
PhD, Sr. Applications Scientist, Agilent
“Qualitative and Quantitative Analysis of Lipids using SFC and LC combined with High Resolution Accurate Mass MS”
Program
5:30 pm – Social and registration
6:15 pm – Complimentary dinner
7:00 pm – Welcome and opening remarks
7:05 pm – Dr. Avizonis
8:00 pm – Dr Lau
8:55 pm – Closing remarks
(Past Events)
Mar 11, 2014 – MSDG Meeting
The NJ Mass Spectrometry Discussion Group presents its March Meeting on Tuesday, Mar 11, 2014 at at the Holiday Inn Somerset-Bridgewater, 195 Davidson Ave, Somerset NJ 08873
Sponsored by Bruker Daltonics Inc
Attendance is free of charge, compliments of our sponsors!
Please register here.
Featured Speakers
I. Jason W. Wood
PhD, Market Manager – Pharma/Biopharma Bruker Daltonics Inc.
“Real or Artifact? Getting Closer to Reality in Biotherapeutic Characterization”
II. Keith Johnson (co-authors: Heather DeGruttola, Andrew Saati, Lisa A. Marzilli and Jason C. Rouse)
Mass Spectrometry and Biophysical Characterization Group, Analytical Research and Development, BioTherapeutics Pharmaceutical Sciences, Pfizer Inc
“Applications of Ultrahigh-Resolution Mass Spectrometry to Biotherapeutics Characterization”
Program
5:30 pm – Social and registration
6:15 pm – Complimentary dinner
7:00 pm – Welcome and opening remarks
7:05 pm – Dr. Jason Wood
8:00 pm – Dr. Keith Johnson
8:55 pm – Closing remarks
Abstract for Talk I:
There are many tools available for the characterization of biotherapeutics including advanced hardware and software as well as multiple novel enzymes for digesting large molecules into specific fragments for further analysis in a more ‘bottom-up’ approach. However, enzymatic digests can lead to artifacts which may further complicate the analysis of these large biomolecules. Here we present a workflow for the analysis of antibodies with minimal enzymatic digestion and MALDI-TOF/TOF analysis, allowing for fewer artifacts and more accurate characterization”
Abstract for Talk II:
Therapeutic proteins are characterized methodically with respect to primary structure, posttranslational modifications, charge and size heterogeneity, higher order structure, and biological activity, in concert with process and product development, to achieve a comprehensive understanding of the active substance prior to commercialization. The ESI-quadrupole-time-of-flight (QTOF) mass spectrometer is well-established in the heightened characterization of protein therapeutics, and is highly suited for antibodies, antibody-drug conjugates, fusion proteins, novel constructs, and vaccines. This single instrument platform provides detailed structural information for the intact protein molecule, as well as for the subunits/domains, proteolytic peptides, and released N-glycans (if present) in orthogonal analyses. The newest generation of ultrahigh-resolution (UHR) ESI-QTOF mass spectrometers offers significant improvements in critical performance parameters such as resolution, mass accuracy, sensitivity and dynamic range. These instruments, in conjunction with new approaches to protein characterization, provide accurate measurements to within 2 ppm of theoretical values for isotopically-resolved proteins ≤35 kDa, which is ideal for the detailed analysis of whole antibody subunits/domains and smaller single-chain proteins.
In this presentation, a comparison of newer LC/MS-subunit analysis methods for antibody characterization will be discussed that improve on traditional reduction/alkylation, and light and heavy chain subunit mass analysis. Through hinge region-proteolysis and disulfide bond reduction, heavy chain (~50 kDa) essentially can be cleaved homogeneously into two domain fragments (~25 kDa each) with molecular masses more similar to light chain (~24 kDa). Since UHR QTOF MS excels in this 10-35 kDa mass range, these newer approaches to subunit analysis afford more sensitive detection and definitive identification of both expected and unexpected antibody modifications at the whole subunit/domain level, all in a rapid manner – in contrast to traditional, data-intensive proteolytic mapping at the peptide level. In addition, rapid confirmation of the amino acid sequence at the subunit/domain level and detection of potential sequence variants and mis-incorporations during the early stages of process development will be demonstrated with these new methods. Finally, current endeavors regarding automated data analysis for all LC/MS methods will be presented.
(Past Events)
Nov 5, 2013 – MSDG Meeting
Note: There are two meetings coming up soon:
The NJ Mass Spectrometry Discussion Group presents its November Meeting on Tuesday, Nov 5, 2013 at at the Holiday Inn Somerset-Bridgewater, 195 Davidson Ave, Somerset NJ 08873
Sponsored by AB Sciex
Attendance is free of charge, compliments of our sponsor!
Please register here.
Featured Speakers
I. Chongwoo Yu, Ph.D.
Senior Clinical Pharmacology Reviewer Office of Clinical Pharmacology (OCP), Office of Translational Sciences (OTS), Center of Drug Evaluation and Research (CDER), U.S. Food and Drug Administration
“The Role of Bioanalysis in Drug Development”
II. St John Skilton, Ph.D.
Sr. Manager Global Markets, Biologics, AB SCIEX
“Biologics Workflow: How Can We Move from Complex Samples to Direct Answers?”
Program
- 5:30 pm Social and registration
6:15 pm Complimentary dinner
7:00 pm Welcome and opening remarks
7:05 pm Dr. Chongwoo Yu
8:00 pm Dr. St John Skilton
8:55 pm Closing remarks
Abstract for Talk I:
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Clinical Pharmacology plays an important role in drug development, including the evaluation of the drug’s pharmacokinetics (PK), pharmacodynamics (PD), drug interaction potential, exposure-response relationship, and safety considerations when being used in specific populations.
Clinical Pharmacology data is pivotal in delivering the right drug, in the right dose, at the right time, to each particular patient and it has significantly influenced the risk/benefit assessment and labeling recommendations. Consequently, the reliability of that data is of considerable importance and bioanalysis is the solid footing in drug development ensuring the reliability. Bioanalytical data and documentation from method validation or clinical trials are critical elements supporting regulatory submissions such as new drug applications (NDAs) or biologics license application (BLAs).
Case examples will be presented to highlight the utility and importance of bioanalysis in drug development to ensure that drug products are safe, effective, and given at the right dose.
Abstract for Talk II:
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The last few years have seen an abundance of biologics (from peptides to monoclonal antibodies) entering the pharmaceutical pipeline, and it is believed that in the next few years, the pharmaceutical pipeline will contain nearly 50% biologics. In addition, with the patent expiration of several biologics recently, and many more scheduled to come off patent in the future, there is likely to be a steady rise in the number of biosimilars on the market. However, developing robust and reproducible LC/MS or sensitive LC/MS/MS methodologies to characterize and quantify these diverse compounds is significantly more complicated from those developed for small molecules. An evolving regulatory environment, particularly in the late stage studies for both innovator biologics and follow-on biosimilars, adds to this complexity.
As a result there is an increased demand for simple workflows using LC/MS or LC/MS/MS that offer users the ability to develop sensitive, robust, and reproducible methods that address regulatory demands as required. This talk will highlight the workflows that were used for characterization of the key features of Biologics using an LC/MS platform with time-of-flight technology, inclusive but not limited to: advanced peptide mapping, whole protein analyses, Antibody Drug Conjugate characterization, sequence variant analysis, and identification and quantitation of Host Cell Proteins.
(Past Events)
Oct 22, 2013 – MSDG Meeting
Note: There are two meetings coming up soon:
The NJ Mass Spectrometry Discussion Group presents its October Meeting on Tuesday, Oct 22, 2013 at at the Holiday Inn Somerset-Bridgewater, 195 Davidson Ave, Somerset NJ 08873
Sponsored by Shimadzu Scientific Instruments
Attendance is free of charge, compliments of our sponsor!
Please register here.
Featured Presentations and Speakers
I. Dr. Fred Regnier
Professor Emeritus & John H. Law Distinguished Professor of Chemistry Purdue University and Novilytic Laboratories
“Mass-Linked Immuno-Selective Analysis and Next Generation Plasma Collection Technology For Clinical and Pharmaceutical Applications”
II. Dr. Christopher Gilles
“Accelerating Therapeutic Antibody Analysis and Next Generation Plasma Screening with Ultra-Fast Mass Spectrometry”
Program
- 5:30 pm Social and registration
6:15 pm Complimentary dinner
7:00 pm Welcome and opening remarks
7:05 pm Dr. Fred Regnier
8:00 pm Dr. Christopher Gilles
8:55 pm Closing remarks
Abstract for Talk II:
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Introduction — Because monoclonal antibodies (mAbs) are increasingly an important line of therapeutics for the biopharmaceutical industry, the demand to better understand the biochemical and biophysical properties of mAbs has become critical. Recent developments in native protein mass spectrometry (MS) have clearly shown its distinctive power for characterization of intact proteins and protein conjugates. The mass spectrometry–based study of intact mAbs in native-like states provides a wealth of information to interpret its biological features. This is the first reported use of a commercial Orbitrap mass analyzer for measuring a native intact mAb protein. A monoclonal IgG1 kappa antibody, composed of two heavy chains of 451 amino acids and two light chains of 213 amino acids was characterized in this study.
Methods — The mAb was analyzed using normal flow liquid chromatography (LC)-MS method. The intact mAb protein was eluted from a size exclusion column under non-denaturing and non-reducing conditions and then directly detected by a standard stock bench-top Orbitrap mass spectrometer under full scan MS mode. The AGC target was set at 3e6 with resolution at 17,500. The MS spectrum was then analyzed with protein deconvolution software (Protein Deconvolution 2.0) that utilizes the ReSpect algorithm for molecular mass determination.
Results — To monitor the IgG1 kappa in native-like state, the protein was dissolved under non-denatured and non-reduced conditions. The protein was then chromatographically eluted from a size exclusion column and directly analyzed online using an Orbitrap mass spectrometer with high mass range. The mass spectra from LC-MS analyses of the native intact antibody demonstrate a clean distribution of the multiply charged envelope at mass range above 5000 m/z. Individual charge states in the raw mass spectrum for the native antibody shows major glycosylation species. Results from this study demonstrate an efficient and potentially high through-put workflow for antibody measurement in native-like states. This protocol, using a combination of normal flow size exclusion LC and a HR/AM bench-top Orbitrap mass spectrometer is expected to provide important data for mAb studies.
Novel Aspect — Native Intact Monoclonal Antibody was analyzed by a standard stock bench-top Orbitrap mass spectrometer
(Past Events)
Oct 9, 2013 – MSDG Keynote Lectures & Awards at CPSA
Note: There are three meetings this month:
The NJ Mass Spectrometry Discussion Group will participate in the
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Keynote Lectures & Awards
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(Past Events)
Oct 7, 2013 – MSDG organized session at CPSA
Note: There are three meetings this month:
The NJ Mass Spectrometry Discussion Group presents the
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MSDG Organized Session at
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Session Details
From Screen Hit to Bedside Medicine:
Time: 12:00 – 4:30, Monday, October 7, 2013
Venue: University I Ballroom
Sponsor: Silicon Kinetics
Discussion Leaders: Ron Kong, PTC Therapeutics; Fangbiao Li, Merck
Talk 1:
Applying Nano Porous Silicon Technology to Affinity Kinetics and its Linkage to Mass Spectrometry
Keith Waddell, Silicon Kinetics
Talk 2:
Caught in a Bind: Antibodies for Current and Emerging Technologies
Gordon R. Whiteley, NIH
Talk 3:
Metabolomics in Drug Discovery: Lessons Learned and Path Forward
Petia Shipkova, Bristol-Myers Squibb
Talk 4:
Target-Specific Protein Quantitation by LC-MS/MS
Bob Xiong, Tandem Labs
Talk 5:
Thought on the Biomarker Pipeline
Randy Nelson, Arizona State University
Talk 6:
Error Proofing: Maximizing Productivity by Getting it Right the First Time
Lucinda Cohen, Merck
(Past Events)
Sep 12, 2013 – MSDG Vendor Show & Vendor Sponsored Workshop
The NJ Mass Spectrometry Discussion Group presents the
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2013 Fall Vendor Show & Vendor Sponsored Workshop
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Attendance is free of charge, compliments of our sponsor!
Please register here.
Featured Speakers
I. Dr. Kevin Bateman
Merck & Co
II. Professor Gary Glish
University of North Carolina at Chapel Hill
“The New Tandem MS: Ion Mobility Spectrometry/Mass Spectrometry”
Program
- 1:30 – 7:00 PM Vendor Set Up & Registration – Hotel Ballroom
1:30 – 7:00 PM Vendor Show
3:30 – 4:15 PM Workshop Session
4:15 – 4:45 PM Cocktail Break / vendor interaction
4:45 – 5:45 PM Presentation by Dr. Kevin Bateman
5:45 – 7:00 PM Buffet Dinner (Raffle prizes will be announced)
7:00 – 8:00 PM Presentation by Professor Gary Glish
Abstract for Talk II:
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Tandem mass spectrometry (MS/MS) is one of the most powerful methods available to the modern analytical chemist. However, as instruments become more and more sensitive there is an increasing challenge of isomeric and isobaric ions interfering with the analysis. The conventional approach to overcoming this problem is to use chromatography to separate analytes prior to ionization. While LC is a powerful analytical technique in its own right, it has some limitations when combined with mass spectrometry. A couple of important limitations are that the time frame of a chromatography separation is much slower than mass spectrometry (minutes to hours vs. seconds or less), and the order of analyte analysis cannot be adjusted in real-time. And for some real-time analyses, chromatography is not even an option.
As an alternative to chromatographic separations, we are developing differential ion mobility spectrometry (DIMS) as a separation method prior to mass spectrometry. While mass spectrometry separates ions based on their mass-to-charge ratio, conventional drift tube ion mobility spectrometry (DTIMS) is based on the ions’ shape-to-charge ratio. For DIMS the separation mechanism is not totally understood and while shape-to-charge plays a role, other factors such as the ion interaction with the drift gas are important. This makes DIMS more orthogonal to MS than DTIMS. DIMS has other differences compared to DTIMS that make DIMS more useful as an alternative to chromatography when combined with MS. In this presentation the fundamentals of DIMS will be discussed. Examples will be shown using DIMS/MS to analyze isobaric peptides, aerosols in real-time, and targeted compounds in complex matrices.
(Past Events)
Jun 18, 2013 – MSDG Meeting
The NJ Mass Spectrometry Discussion Group presents the June 2013 Meeting on Tuesday, June 18, 2013 at Mirabelle’s Room, DoubleTree by Hilton Somerset, 200 Atrium Drive, Somerset, New Jersey 08873.
Sponsored by Thermo.
Attendance is free of charge, compliments of our sponsor!
Please register here.
Featured Speakers
I. Jonathan Josephs, Ph.D
Principal Scientist, Bristol-Myers Squibb
“Creation of Rich MSn Data for Structure Elucidation in Quan/Qual Analysis: Applications of Combined HCD/CID and New Isolation Techniques”
II. Dr. Jie Qian
“Orbitrap Analysis of Native Intact Monoclonal Antibody”
Program
- 5:30 pm Social and registration
6:15 pm Complimentary dinner
7:00 pm Welcome and opening remarks
7:05 pm Jonathan Josephs
8:00 pm Jie Qian
8:55 pm Closing remarks
Abstract for Talk II:
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Introduction — Because monoclonal antibodies (mAbs) are increasingly an important line of therapeutics for the biopharmaceutical industry, the demand to better understand the biochemical and biophysical properties of mAbs has become critical. Recent developments in native protein mass spectrometry (MS) have clearly shown its distinctive power for characterization of intact proteins and protein conjugates. The mass spectrometry–based study of intact mAbs in native-like states provides a wealth of information to interpret its biological features. This is the first reported use of a commercial Orbitrap mass analyzer for measuring a native intact mAb protein. A monoclonal IgG1 kappa antibody, composed of two heavy chains of 451 amino acids and two light chains of 213 amino acids was characterized in this study.
Methods — The mAb was analyzed using normal flow liquid chromatography (LC)-MS method. The intact mAb protein was eluted from a size exclusion column under non-denaturing and non-reducing conditions and then directly detected by a standard stock bench-top Orbitrap mass spectrometer under full scan MS mode. The AGC target was set at 3e6 with resolution at 17,500. The MS spectrum was then analyzed with protein deconvolution software (Protein Deconvolution 2.0) that utilizes the ReSpect algorithm for molecular mass determination.
Results — To monitor the IgG1 kappa in native-like state, the protein was dissolved under non-denatured and non-reduced conditions. The protein was then chromatographically eluted from a size exclusion column and directly analyzed online using an Orbitrap mass spectrometer with high mass range. The mass spectra from LC-MS analyses of the native intact antibody demonstrate a clean distribution of the multiply charged envelope at mass range above 5000 m/z. Individual charge states in the raw mass spectrum for the native antibody shows major glycosylation species. Results from this study demonstrate an efficient and potentially high through-put workflow for antibody measurement in native-like states. This protocol, using a combination of normal flow size exclusion LC and a HR/AM bench-top Orbitrap mass spectrometer is expected to provide important data for mAb studies.
Novel Aspect — Native Intact Monoclonal Antibody was analyzed by a standard stock bench-top Orbitrap mass spectrometer
(Past Events)
May 7, 2013 – MSDG Meeting
The NJ Mass Spectrometry Discussion Group presents the May 2013 Meeting on Tuesday, May 7, 2013 at the Holiday Inn Somerset-Bridgewater, 195 Davidson Ave, Somerset NJ 08873. Sponsored by Agilent Technologies.
Attendance is free of charge, compliments of our sponsors!
Please register here.
Featured Speakers
I. Xinping Fang, Ph.D
VP, Head of Bioanalytical & Acting Head of Drug Metabolism / Biotransformation, XenoBiotic Laboratories, Inc, Plainsboro, NJ.
“Implementing an Ultrasensitive and Advanced New LC-MS/MS Platform, Xevo TQ-S, in a Regulated BA Lab”
II. Paul Rainville
Senior Manager of Scientific Operations, ESD, Pharmaceutical & Life Sciences Business Operations. Waters Corporation
“Advances in Front-End Technologies for Bioanalysis”
Program
- 5:30 pm Social and registration
6:15 pm Complimentary dinner
7:00 pm Welcome and opening remarks
7:05 pm Xinping Fang
8:00 pm Paul Rainville
8:55 pm Closing remarks
Abstract for Talk II:
Modern bioanalytical chemists are charged with the task of developing high sensitivity assays for drug candidates with low circulating concentration, typically in the single pg/mL range. If this challenge was not difficult enough new economic, study design and ethical pressures demand that increasingly small volumes of samples are required and new sample formats such as dried blood spots. In this paper we will discuss the relative merits and pitfalls of two-dimensional liquid chromatography for bioanalytical applications when coupled to tandem quadrupole MS. Two-dimensional chromatography was evaluated for two applications i) to improve analyte cleanliness, thus increasing assay sensitivity and ii) to allow the direct injection of organic solvents onto a reversed phase system. As part of the study the mode of 2D operation was evaluated; forward flush, back flush and heart cut. Also we will discuss the use of a micro fabricated ceramic device packed with sub 2ìm for the analysis of plasma, bile and urine samples. We will show how the use of the micro scale separations device has been employed for the analysis of both small and large molecules.
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2021 Baekeland Award
The North Jersey Section of the American Chemical Society will award the 2021 Leo Hendrik Baekeland Award on May 12, 2022, to Dr Prashant K. Jain.
The Section presents the Award biennially to commemorate the technical and industrial achievements of Leo Hendrik Baekeland and to encourage younger chemists to emulate his example.
Message From Justyna Sikorska
It is a great honor to serve as Chair for 2023. I look forward to leading this incredible and diverse group of volunteers . . . My goals for 2023 start with supporting our diverse topical groups and committees in organizing exciting seminars . . .
