performance of new 400 mhz hts power-driven magnet … · power-driven magnet nmr technology on...

PANIC NMR 2018

MARIA VICTORIA SILVA ELIPE*, NEIL DONOVAN, ROBERT KRULL, DONALD POOKE, KIM COLSON

PERFORMANCE OF NEW 400 MHZ HTS POWER-DRIVEN MAGNET NMR TECHNOLOGY ON CINACALCET HCL (TYPICAL API IN PHARMA)

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Provided March 6, 2018, as part of an oral presentation and is qualified by

such, contains forward-looking statements, actual results may vary

materially; Amgen disclaims any duty to update.

• Historical highlights of magnet development

• Symbiotic scientific collaboration

• Scheme of the instrument

• Cinacalcet HCl

• NMR data (1D 1H, 2D COSY, 2D NOESY, 2D 1H-13C HSQC)

• HTS NMR system installed at Amgen chemistry laboratory

• Pros and cons of HTS magnet system

• Acknowledgements

• Thank you

OUTLINE

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HISTORICAL HIGHLIGHTS OF MAGNET DEVELOPMENT

0

200

400

600

800

1000

1200

1951

1955

1958

1965

1970

1973

1970

1980

2010M

ag

neti

c f

ield

fo

r P

roto

n (

MH

z)

Year

Increase on MHz over the years

Cryogenic

magnets

Electromagnets

Permanent

magnets

HTS magnets

superconducting at ~18 K

0

50

100

150

200

250

300

350

400

450

1950s-60s 2013 2017

Ma

gn

eti

c F

ield

fo

r P

roto

n (

MH

z)

Year

Electromagnets

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SYMBIOTIC SCIENTIFIC COLLABORATION

Amgen

Bruker BioSpin

HTS-110

Maria is happy!

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SCHEMATICS OF THE INSTRUMENT

console

computer

chiller He compressor

power supply

magnet monitor

400 MHz

HTS magnet

sample

Silva Elipe, MV, Donovan, N, Krull, R, Pooke, D, Colson, K, 2018, submitted

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• API of commercial oral formulated tablets of Sensipar®/Mimpara®

• Approved in 2004 by FDA as Sensipar® and by EMEA as Mimpara®

• Therapeutic indications:

– Secondary hyperparathyroidism (sHPT) for patients with chronic kidney disease

(CKD) on dialysis

– Primary hyperparathyroidism and parathyroid carcinoma

CINACALCET HCL

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COMPARING 1D 1H NMR ALIPHATIC REGION OF HTS NMR SYSTEM WITH CONVENTIONAL NMR INSTRUMENT


Magnet up time: days Magnet up time: years

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COMPARING 1D 1H NMR AROMATIC REGION OF HTS NMR SYSTEM WITH CONVENTIONAL NMR INSTRUMENT


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COMPARING 2D COSY OF HTS NMR SYSTEM WITH CONVENTIONAL NMR INSTRUMENT


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COMPARING 2D NOESY OF HTS NMR SYSTEM WITH CONVENTIONAL NMR INSTRUMENT


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COMPARING 2D 1H-13C HSQC OF HTS NMR SYSTEM WITH CONVENTIONAL NMR INSTRUMENT


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COMPARING 1D 1H NMR OF HTS NMR SYSTEM (BBFO/BOSS3 AND QNP/BOSS1) WITH CONVENTIONAL NMR INSTRUMENT


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COMPARING 1D 1H NMR ALIPHATIC REGION HTS NMR SYSTEM (QNP/BOSS1) WITH CONVENTIONAL NMR INSTRUMENT


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HTS NMR SYSTEM INSTALLED AT AMGEN CHEMISTRY LAB

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Pros:

• No need to fill with liquid cryogens (no liquid

N2 and He needed) and no O2 sensors

• Easy access to chemist (in the same lab with

no restricted access)

• Small footprint magnet (can site in hood,

easy sample insertion, small stray field)

• Quick installation (couple of days to field and

acquiring data)

• Ability to shutdown magnet during times of

non-use (easy to do by the user, no need for

engineer, magnet can be easy moved to

other location if needed, no need for extra

money)

PROS AND CONS OF HTS MAGNET SYSTEM Cons:

• Sensitive to power

outages (UPS/generator

needed)

• Compressor & power

supply must be nearby

(real-estate)

• Water cooling or air-

cooling needed

• Noisy equipment (He

compressor)

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• Amgen Sponsors: Janet Cheetham & David Semin

• Cinacalcet HCl sample from Amgen: Minhui Ma & Robert

Munger

• Bruker BioSpin: Clemens Anklin

• Others: many people helped through the process

ACKNOWLEDGEMENTS

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THANK YOU

Elvis is alive and has been working

with a cryogenic magnet for decades

No cryogens????

But now …

Oops!!!

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