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John Edwards MNova User Meeting - SMASH - 9-22-13
1. Process NMR Associates
Utilization of MNova in a Commercial NMR Testing Laboratory for :
1) Development of Automated Quantitative Analysis Methods by
Direct Internal Standard NMR Measurements, and
2) Pre-Processing of Large NMR Datasets for Chemometric
Regression Analyses to Derive Chemical and Physical Properties
John Edwards
Process NMR Associates, LLC, Danbury, Connecticut
September 22, 2013
MestreLab MNova Users Meeting, SMASH 2013
Santiago de Compostela, Spain
2. Process NMR Associates
250+ Analytical NMR Customers
TTC Labs, Inc.
Process Engineering Excellence
Analytical
Services
And
Consulting
TopNIR Systems
3. Process NMR Associates
Quantitative 1H qNMR Method for Complex Mixture Analysis: Determination of
Acetylated Polysaccharides, Glucose, Maltodextrin, Isocitrate, Malic Acid in
Aloe Vera Leaf Juice.
Also … Preservatives, Additives, and Degradation Products in Aloe Vera Raw
Materials and Consumer Products
Presented By
John Edwards, Ph.D.
Process NMR As
sociates, LLC
Danbury, Connecticut
November 9, 2012 Aloe Summit, Las Vegas, NV
Development of Automated Quantitative Analysis Methods by Direct Internal
Standard NMR Measurements
4. Process NMR Associates
NMR Systems and Experimental Conditions
Acquisition Time
Relaxation (Recycle) Delay
Frequency, MHz
Nucleus
Number of Pulse Accumulations*
Original FID Points
Zero-filled Points
Pulse sequence
Solvent
Sweep width, ppm
Temperature
Line Broadening
Steady State Pulses
Pre-Acquisition Delay
3-8 Seconds
2-6 Seconds
300-500 MHz
1H
16-256
16384-84000
32768-262144
Single pulse
D2O
16
Ambient (25 ºC)
0.35 Hz
8
60 seconds
5. Process NMR Associates
Advantages of Using NMR in Complex Mixture Analysis
• Minimal Sample Preparation
• Reproducible (site to site, country to country)
• Linear and Quantitative Spectral Response
• Targeted AND Non-Targeted
• Qualitative
• Quantitative
• Compound Specific
• Rapid – 10 Minutes
• Affordable
6. Process NMR Associates
Aloe Vera Inner Leaf Juice Constituents and Additives that need to be
Analyzed and Reported for IASC Certification
Compound
Acemannan
Acetylated PS
Glucose
IASC Certification requirement
≥ 5% dry weight
Present
Aloin
10 ppm or less in 0.5% aloe vera solids solution, analysed by
HPLC or other fit for purpose methodology approved by IASC
Isocitrate
≤ 5% dry weight
Maltodextrin
Must be listed on label and analysis must meet label claims. If
undeclared, is considered an adulterant.
Solids
Ash
≥ 0.46% in single-strength juice (for example, a 10x
concentrate should have ≥ 4.6%)
≤ 40%
7. #
# Chemical Characterization of the Immunomodulating Polysaccharide of Aloe Vera L., W.J.Goux, et al,
http://www.iasc.org/AloeStructure080604.pdf
10. Process NMR Associates
Chemical shift values, peak and chemistry descriptions, molar conversion factors that can be
used for detection and quantitation of aloe vera leaf juice preservatives, additives, and
degradation products
Compound
Type of compound
Signal type
Propylene glycol
Ethanol
Lactic acid
Potassium sorbate
Additive
Degradation product or additive
Degradation product
Preservative
CH3, doublet (N=3)
CH3, triplet (N=3)
CH3, doublet (N=3)
CH3, doublet (N=3)
Chemical shift,
ppm
1.1
1.15
1.33
1.82
Acetic acid
Pyruvic acid
Citric acid
CH3, singlet (N=3)
CH3, singlet (N=3)
2 x CH2, Multiplet (N=4)
1.96
2.35
2.5-3.0
Succinic acid
Glycerol
Glycine
Sucrose
Fumaric acid
Sodium benzoate
Degradation product
Degradation product
Naturally present or added as pH
regulator or preservative
Degradation product
Additive
Additive
Additive
Degradation product
Preservative
2 x CH2, singlet (N=4)
CH2 and CH, multiplet
CH2, singlet (N=2)
CH, doublet (N=1)
2 x CH, singlet (N=2)
2 x CH, doublet (N=2)
2.6
3.5
3.51
5.4
6.5
7.95
Formic acid
Degradation product
CH, singlet (N=1)
8.2-8.3
19. Process NMR Associates
2) Pre-Processing of Large NMR Datasets for
Chemometric Regression Analyses to Derive Chemical
and Physical Properties
20. Process NMR Associates
Third Generation NMR - 2013– Aspect AI NMR System
New magnet design – 30mm bore size
•
The amount of magnetic pieces that assemble the magnet reduced from 34 to 10. Reduction in
Mechanical Complexity
•
Bore size of the magnet was increased to 30 mm - improved temperature susceptibility
•
Improved temperature and shim stability.
New Digital Spectrometer Design - reduces footprint, improves signal processing capabilities
Probe - Improved Probe Q for Higher Sensitivity.
Software – Windows 7 – Improved Chemometric Capabilities
Lab version
On-Line version
21. Process NMR Associates
Pulsar
60 MHz NMR
3-5 mm Samples
Lab Only
42 MHz NMR
3-5 mm Samples
Lab Only
NMReady 60
60 MHz NMR
3-5 mm Samples
Lab Only
September 12, 2013
Fourier 60
MobiLab™ SPECTRA 2T
60 MHz NMR
3-5 mm Samples
Lab Only
85+ MHz NMR
3-5 mm Samples
Lab Only
Picospin 45 and 80
45 MHz and 82 MHz NMR
300 micron capillary injection
Lab Only
aspectimaging
60 MHz NMR
3-10 mm Samples
Lab or On-Line
60 MHz NMR
3-10 mm Samples
Lab or On-Line
31. Process NMR Associates
Transposed CSV Output of Stacked Plot – Yields rows that have integration bin values
Input as X Variable Data into Chemometrics Software Packages
32. PLS Regression Analysis to Obtain Predictive Model of
EPA and DHA Omega-3 Fatty Acids at Various Points
Of Nutritional Supplement Manufacturing Process
EPA (Area %)
0.64
21.55
62.97
29.43
14.21
52.74
15.21
7.18
16.95
36.35
61.09
13.32
71.78
41.40
1.19
11.73
43.38
6.07
9.77
58.93
10.62
43.91
54.05
0.00
26.97
DHA (Area %)
0.01
13.34
15.66
18.16
9.54
28.90
10.51
0.23
10.04
16.47
21.26
5.95
7.43
25.91
0.06
12.23
19.30
2.78
0.72
23.41
5.18
21.52
28.18
0.00
12.82
Sample Description
First Esterification
First Esterification
Clathration
Mol Dist
Pollock Oil
Separator
PolyUnsat Ester
First Esterification
First Esterification
Clathration
Mol Dist
MSC Pollock Oil
Separator
PolyUnsat Ester
First Esterification
First Esterification
Clathration
Clath Raffinate
First Esterification
Mol Dist
MSC Pollock Oil
Separator
PolyUnsat Ester
First Esterification
First Esterification
600
500
400
300
Data
NMR ID
FO3h001
FO3h002
FO3h003
FO3h004
FO3h005
FO3h006
FO3h007
FO3h008
FO3h009
FO3h010
FO3h011
FO3h012
FO3h013
FO3h014
FO3h015
FO3h016
FO3h017
FO3h018
FO3h019
FO3h020
FO3h021
FO3h022
FO3h023
FO3h024
FO3h025
200
100
0
-100
1
2
3
4
5
6
Variables
7
8
9
10
11
37. Process NMR Associates
Acknowledgements
Paul Giammatteo – PNA
Tal Cohen – ASPECT AI and Modcon
Adam Dicaprio, Daniel Edwards – PNA
Mike Bernstein – MestreLabs (SMA Development)
For more information and applications visit www.process-nmr.com