THE Q IN NMR A REVIEW OF RECENT INTERNATIONAL ACTIVITIES

Transcription

1 THE Q IN NMR A REVIEW OF RECENT INTERNATIONAL ACTIVITIES Torsten Schoenberger 1, Kim Colson 2, Michael Maiwald 3 1 Bundeskriminalamt (BKA), Wiesbaden, Germany 2 Bruker BioSpin, Billerica, MA, USA 1 Bundesanstalt für Materialforschung und -prüfung (BAM), Berlin, Germany November 24th,

2 The in NMR Spectroscopy qnmr Spectroscopy First initiative towards a worldwide agreement Identifying a network of NMR people concerned with validation Assisting each other through the validation process Harmonizing the terminology Agreeing a standard approach for NMR validations Position the guidelines so that accreditation agencies can use this process Recent activities and their outcome Resources Future activities The qnmr Summit Logo The q Artwork and the qnmr Summit Logo are by Guido Pauli and licensed under a Creative Commons Attribution-ShareAlike 4.0 International License. The license can be found at by-sa/4.0/legalcode. 2

3 What is NMR? Nuclear Magnetic Resonance 1. Dissolve material (and internal standard) in NMR solvent 2. Place NMR tube in magnet 3. Excite sample with RF pulse 4. Record RF signal for several seconds IS materia l NMR tube Molecules stay intact See everything in solution ( 1 H, 13 C, 19 F, 31 P) Direct comparison of mole fractions No ionization, no UV Detailed information, molecular makeup, structural information, radio frequency pulse individual NMR signals answer signal FT 5. Fourier transform the answer signal 6. Individual molecular segments exhibit highly resolved individual signals 7. Signal areas (integration) are directly proportional to mole fractions 3

4 What Makes qnmr Different Pros Easy sample preparation Relatively short analysis times Simple method development Instrument independent Absolutely linear (LOQ to 100 %) No matrix effects Reliable Precise Multiple calibration options Cons without need for identical reference material Limit of detection in low μm range (compared to MS in low nm to pm range) Applications Purity determination Certification Drug metabolism Quality control Quantitation Quality control Reaction monitoring Metabolomics Drug metabolism Drug characterisation Diagnostics) Chemometrics Group differentiation Drug and natural products classification 4

5 Primary Analytical Reference Methods Fundamental Relationship of qnmr signal intensity I x is directly proportional to the number of nuclei N x responsible for that particular resonance I x ~ N x i.e. I x = K s N x where K s is the spectrometer constant and remains the same for all resonances in an NMR spectrum. i.e. and for a molar ratio Factors that affect K s are (a) pulse excitation (that should be uniform throughout the spectral width) (b) repetition time (should be 5 7 times T 1 ) (c) broad-band decoupling, which causes inherent distortion in intensity due to the Nuclear Overhauser Effect (NOE) 5

6 qnmr Protocols 3 Key Issues! Sample preparation (weighing) should be treated separately Proposed method Assure adequate selectivity in appropriate solvent one orienting measurement selection of internal standard (database) Test of interactions/reactions between analyte and internal standard sample above may serve for stability tests T 1 determination quantitative relaxation Determination of sufficient number of scans (sufficient signal-to-noise) and requirement on the minimum allowable sample weight 6

7 Acquisition Parameters for 1 H qnmr My First Quantitative Pulse Sequence Quantitative relaxation 5 x T % 7 x T % F. Malz, H. Jancke, Journal of Pharmaceutical and Biomedical Analysis 38 (2005) Adequate signal to noise ratio 7

8 PANIC Validation Workshop Upcoming Join us March 4th-8th, 2018 in La Jolla, CA, USA >50 Attendees Demographics Industry Service providers Government Academia qnmr, chemometrics, gov. perspective, terminology, regulations, method dev. Pictures from 2017 & 2016 Workshops Work Groups Flash Presentations Talks Vito Gallo: Interlab Comparisons Discussions Elina Zailer: Round Robin Tests Connections Markus Obkicher: Reference Materials 8

9 Founding Principles and Goals We are all in this together Identify a network of NMR people concerned with validation that can ultimately assist each other through the validation process, Harmonize the terminology and a standard approach for NMR validations, Position the guidelines produced by consensus of the NMR community so that accreditation agencies can use this process. Validation of NMR: No Need to PANIC 9

10 Major Accomplishments Sponsorship Opportunities Available Contact: Bruker Fellowship for Excellence in NMR Validation presented by PANIC Provide education in NMR validation through fostering communication on NMR validation concerns in the community and presentation of results from our meetings and initiatives. Karolien Denef, Kaylen Obray, Claudia Boot, Chris Rithner 1 st Award Recipient (2016) Kaylen Obray Colorado State University, USA 2 nd Award Recipient (2017) Elina Zailer U. Wurzburg / Spectral Service, Cologne, DE Web Presence: Maintain Events, References, NMR Validation Wiki-based website Education Campaign Coordinator: Quarterly Newsletter, Outreach Administration of LinkedIn NMR Validation group Reporter of NMR A review validation of recent international progress qnmr and activities concerns qnmr Day Bari 10

11 Newsletter Submit info to: Interlab comparison info Review of other meetings Upcoming events News flashes that help the progress in the field SMASH 2016 Kim, Kaylen,Claudia 11

12 Wiki A Very Special Thank You to Torsten Schoenberger and Kristie Adams 12

13 Wiki Need an account? Visit: Help us make the ValidNMR Wiki the go-to place for validation protocols and information A go-to place for the analytical chemist just starting out with NMR. 13

14 Join us March 8, 2018 at PANIC Submit your proposal 2018 Workshop Goals and Activities (Preliminary ideas submit your proposals) Want to be a presenter? Contact us at committee@validnmr.com Workshops Talks How to get great qnmr results Why & How to conduct ILCs Terminology familiar to Feds Validation success stories (and how we got there) Measuring uncertainty Interlab Comparison Results Reports from qnmr Summits qnmr ISO Guidelines Small Group Breakouts Wiki : Current Status & Next Steps Join us March 8 in La Jolla, CA 14

15 Activities /2014, Charlotte 2/2016, Houston 9/2016, La Jolla, USA /2015, La Jolla 6/2016, Cologne, D 10/2016, Rockville, USA The qnmr Summit Logo The q Artwork and the qnmr Summit Logo are by Guido Pauli and licensed under a Creative Commons Attribution-ShareAlike 4.0 International License. The license can be found at 15

16 Activities /2017, Hilton Head Island, USA Sep. 2017, SMASH, Baveno, I 2017 March 2017, BAM, Berlin, D Nov. 2017, University Bari, Bari, I 16

17 Summit with USP Rockville, USA (October 2016) 2 Days The first qnmr Summit 2016 was held on October 6+7, 2016 at the Headquarters of the United States Pharmacopoeia (USP) in Rockville, MD (USA). It was organized by the USP and the Center for Natural Product Technologies (CENAPT) of the University of Illinois at Chicago College of Pharmacy. first day: talks (bigger group) second day: discussion (smaller expert group, ~35) dozens of flash presentations nomenclature specific methods best practice manuals education excellent proceedings, not yet in WWW Materials from this event are currently being compiled for dissemination. The qnmr Summit Logo The q Artwork and the qnmr Summit Logo are by Guido Pauli and licensed under a Creative Commons Attribution- ShareAlike 4.0 International License. The license can be found at 17

18 SUMMIT 2017 March, 16th 17th 2017 BAM, Berlin, Germany Open Space Workshops Requirements to qnmr Software qnmr interlaboratory comparisons qnmr Method Collection and their individual validation needs Duties and Responsibilities of qnmr validation Setting up the qnmr WIKI upcoming-events/qnmr-summit-2017-berlin Michael Maiwald (BAM) 18

19 Summit held by JP and JEOL Tokyo, Japan (January 29th-30th, 2018 Venue: Fukuracia Marunouchi oazo Monday, Jan. 29th, 2018 International qnmr Forum: Working toward ISO Understanding NMR standards in the world Tuesday, Jan. 30th, 2018 USP Session: Compendial NMR and qnmr: NMR and qnmr in Pharmacopeial Context International qnmr Symposium: qnmr in the pharmaceutical industry: Present and Future Further details to be posted on Takako Suematsu (JEOL RESONANCE Inc.) and Toru Miura (Wako Pure Chemical Industries, Ltd.) Please contact Takako Suematsu or Toru Miura with questions. 19

20 Summit at University of Würzburg Würzburg, Germany (October 2018) Discussion of the current status of qnmr Scientific exchange concerning, ISO17025, validation, ring tests, quantification capabilities, and statistical methods Enhanced cooperation of all qnmr groups at international level Public discussion platform to promote know how transfer Support of co operation for harmonization Tel.: +49 (0) 931 / Fax: +49 (0) 931 / Institut für Pharmazie und Lebensmittelchemie Am Hubland Würzburg 20

21 3 ValidNMR Tools to bring together international efforts 1. Homepage 2. Wiki 3. LinkedIn share information on - events - ILCs - CRMc - coordination of community s knowledge communication platform 21

22 Acknowledgements Thank you! 22