Impurity Profiling of OLED Material Using UPLC/Q-Tof
Waters
Introduction
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Supply chain in product manufacturing
ManufacturingSynthesis
& Purification
Synthesis
& Purification
Raw materials Materials Products
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Quality factors and comparative studies
Raw materials from supplierBatch A vs Batch B
Supplier X vs Supplier Y
Prototype
Product
Trial & Error
Performance
test
Development
Performance Better vs Worse
Brand A
Brand B
Reverse engineeringOwn product vs Competitors
Discharge
ChargeRef : 0 Cycle
Product stability / life cycleReference vs Degradation
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Impurity in manufacturing process
Raw materials
Synthesis
Purification
Evaluate
performance
Manufacturing
Quality control
Impurity in raw materials
Impurity/by-product in synthetic
and purification process
Residual monomer, initiator
Contamination from outside
Development
Shipping
Unknown Impurity Profiling
Scale up/Manufacturing
Target analysis
(Known impurity)
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▪Agenda
– Q-Tof MS and Elucidation workflow
– OLED material and data acquisition for impurity profiling
– Extraction and identification of impurity peaks
–Extraction using common fragment/Neutral loss
–Extraction by comparison with blank sample
–Extraction based on synthetic pathway.
Impurity profiling agenda
Q-Tof MS and Elucidation workflow
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What information we can obtain from Q-Tof ?
TIME
Accurate mass information ex) (C20H19N2O2S)+ = 351 = 351.1162
m/z
351.1162
352.1193353.1161
Monoisotopic
Isotope
High resolution data
m/z
Quadrupole
Tof
All ions detection including isotope
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MSE acquisition mode
Ch1.
Low Energy
Ch2.
High Energy
Quadrupole Collision Tof MS
Low
Energy
High
Energy
Time
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Spectrum alignment
RT
Ch1.
Low Energy
Ch2.
High Energy
RT
RT
RT
m/z
m/z
Align by peak top time
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Workflow for Structural elucidation
RT
Peak
Compound
1) Elucidate formula
from spectrum
m/z
351.1162
352.1193
353.1161
2) Isotope ratio
3) Delta m/z
1) Accurate mass
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Workflow for Structural elucidation
RT
Peak
Compound
1) Elucidate formula
from spectrum
m/z
351.1162
352.1193
353.1161
2) Isotope ratio
3) Delta m/z
1) Accurate mass
2) Search candidate
compound from formula
Database search
.mol file
ChemSketch
Drawing
structure
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Workflow for Structural elucidation
RT
Peak
Compound
1) Elucidate formula
from spectrum
m/z
351.1162
352.1193
353.1161
2) Isotope ratio
3) Delta m/z
1) Accurate mass
3) Evaluate the most
likely candidate by
fragment match
m/z
High energy
Fragment ion
Fragment match
Simulated fragment spectrum
2) Search candidate
compound from formula
Database search
.mol file
ChemSketch
Drawing
structure
OLED material and analytical condition for impurity profiling
15 © 2020 Waters Corporation
OLED material - E709 -
S
N
Ir
CH3
CH3
O
O
2
Red dopant E709
– Bis(2-benzo[b]thiophen-2-yl-
pyridine)(acetylacetonate)iridium(III)
– Formula : C31H23IrN2O2S2
– Monoisotopic mass : 712.08302 g/mol
713.090
711.088
712.091
714.093
715.090
716.091 717.091 718.091
Theoretical spectrum (M+H+)
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Analytical condition
LC condition
– LC : ACQUITY UPLC I-Class
– Column : ACQUITY UPLC BEH C18
2.1 x 50mm, 1.7um
– MP A : 5mM-anmmoium acetate aq
– MP B : Acetonitrile/THF (50/50)
– Flow : 0.4 mL/min
– Temp. : 40 ℃
– PDA : 210 – 400 nm
– Rate : 20 point/sec
Time A(%) B(%) Curve
0 70 30 6
6 10 90 6
8 70 30 11
10 70 30 11
MS condition
– MS :SYNAPT G2-Si
– Ionization : ESI positive
– Mode : MSE
– Capillary : 3.0 kV
– Scan rate : 0.2 sec
– Cone : 30 V
– Collision : Low energy 4 eV
High energy 30-70 eV
– Mass range :m/z = 50 - 1000
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Data acquisition
– Solvent Blank
o Dissolution solvent (THF)
o Used as the reference for comparing with OLED
sample.
– Low concentration sample
o Concentration at which the main component is
not saturated.
o Used as reference for calculating relative
concentration of impurity.
– High concentration sample
o Concentration at which the main component is
saturated.
o Used for identifying low concentration impurity.
BLANK
Time1.00 1.50 2.00 2.50 3.00 3.50 4.00 4.50 5.00 5.50 6.00
%
0
100
Solvent Blank
Low Conc
Time1.00 1.50 2.00 2.50 3.00 3.50 4.00 4.50 5.00 5.50 6.00
%
0
100
Low Conc.
High Conc
Time1.00 1.50 2.00 2.50 3.00 3.50 4.00 4.50 5.00 5.50 6.00
%
0
100
High Conc.
Main component
(not saturated)
Diverter valve
to the waste
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Acquired data of E709
Retention (min)
Inte
nsity (
count)
Inte
nsity (
count)
Mass (m/z)
Mass chromatogram of M+H+
m/z = 713.0903
RT = 4.10
Mass spectrum (High energy)
Fragment 1 = C26H16IrN2S2 = 613.0379
Fragment 2 = C21H11IrNS2 = 533.9957
Fragment 3 = C13H7IrNS = 401.9923
S
N
Ir
CH3
CH3
O
O
2
Extraction and identification of Impurity peaks
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How to extract impurity peak from TIC
In one platform software
Compare with blank sample
Blank
Sample
Blank
Sample
Search from the same fragment
as main component
Low Conc
Time2.00 4.00 6.00
%
0
100
XIC of fragmentSample (High energy)
Main
ImpImp
Same
color
Search from synthetic pathway IrCl3O O
OO
Ir
3
S
NS
N
Ir
CH3
CH3
O
O
2
Imp Imp
Ex 1) Extraction using common fragment/neutral loss
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Extract impurity peaks by common fragment / neutral loss
S
N
Ir
CH3
CH3
O
O
2
F1 = C26H16IrN2S2 = 613.0379
F2 = C21H11IrNS2 = 533.9957
F3 = C13H7IrNS = 401.9923
E709 (M+H+)
m/z = 713.0903
Fragmentation
Imp?
?
Imp?
Imp?
?
Imp
E709High Conc
Time1.00 2.00 3.00 4.00 5.00 6.00
%
0
100
Mass chromatogram
m/z = 613.0379
High energy
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Extract impurity peaks by common fragment / neutral loss
Peak# RT m/z Intensity
#1
#2
#3
#4
#5
#6
#7
TIME
High
Energy
Low
Energy
Peak# RT m/z Intensity Common
Fragment
Found
Fragment
Common
Neutral loss
Found
Neutral loss
#1
#2 Yes 613.0379
#3
#4 Yes 533.9957
#5
#6
#7 Yes 100.0524
TIME
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Extract impurity peaks by common fragment / neutral loss
Add Delete Import
m/z Formula Label Charge
Input fragment m/z or formula
in processing method
Inte
nsity (
count)
Retention (min)
Mass chromatogram
Mass Spectrum
Process
613.03786
Processing method
High energy
Low energy
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Elemental composition of impurity
Elemental composition of precursor ion
– Use precursor ion spectrum in low energy data
Theoretical
MeasuredImpurity Formula
= C31H23IrN2O3S2
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Candidate structure of impurity with common fragment
??
C31H23IrN2O2S2
E709
C26H16IrN2S2
C31H23IrN2O3S2
Imp
C26H16IrN2S2
Common fragment
MSMS
MSMS
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Candidate structure of impurity with common fragment
??
C31H23IrN2O2S2
E709
C26H16IrN2S2
C31H23IrN2O3S2
Imp
C26H16IrN2S2
?
=
C5H7O2
-
? ?- =
C5H7O3
Common fragment
MSMS
MSMS
Candidate
Import
Library
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Fragment match between data & candidate structure
S = Score:
Calculated score of energy for
fragmentation based on chemical bond
Inte
nsity (
count)
Retention (min) m/z
LibraryData
Fragment match
&
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Ex) Impurity with common fragment
Ex 2) Extraction by comparison with blank sample
Blank
Sample
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Binary compare
Peak# RT m/z Intensity
#1
#2
#3
#4
#5
#6
#7
Peak# RT m/z Intensity
#1
#2
#3
#4
#5
#6
#7
Peak# RT m/z Intensity
#1
#2 2.94 729.0851 150,348
#3
#4
#5 4.72 308.2478 99,002
#6
#7
Peak# RT m/z Intensity
#1
#2 - - -
#3 - - -
#4 - - -
#5 4.72 308.2478 98,832
#6
#7
High Conc
Time1.00 2.00 3.00 4.00 5.00 6.00 7.00
%
0
100
6.48
4.232.94
2.74 3.865.444.70
5.81
6.91
BLANK
Time1.00 2.00 3.00 4.00 5.00 6.00 7.00
%
0
100
5.854.722.75
Sample Blank
Compare
Common to
sample & blank
Unique to Sample
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Binary compare In
tensity (
count)
Inte
nsity (
count)
Retention (min) Mass (m/z)
Blank
Sample
Blank
Sample
Compare all peaks in sample and blank
– Compare all peak in low energy data
– Categorize peaks into “sample”, “blank”, or “common”
Name (Sample) Name(Ref) Unique m/z(Sample) m/z(Ref) RT(Sample) RT(Ref)
Common
Sample
Sample
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Discover tool for elucidation
Elucidate
Formula
DB
Search
Fragment
match
Elemental
composition
Database
search
Fragment
match
Low confidenceC26H16N2S2
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Structural elucidation
Not assigned fragments
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Structural elucidation
Neutral loss = Precursor - fragment
= C26H16N2S2 - C21H11NS2
= C5H5N
Elemental composition
C21H11NS2
Not assigned fragments
N
Impurity may include
this functional group
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Structural elucidation
Library
Import
Draw structure
.mol file
Process
Assigned fragment
More confidence
on elucidation
Ex 3) Extraction based on synthetic pathway
IrCl3O O
OO
Ir
3
S
NS
N
Ir
CH3
CH3
O
O
2
Imp Imp
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Synthetic pathway
IrCl3O O
O
O
Ir
33
OLED material : Ir(ppy)3
Reflux Reflux
in Glycerol
Ir(ppy)3
Ir
N
N
IrCl3O
O
Ir
3
S
N S
N
Ir
CH3
CH3
O
O
2
OLED material : E709
Reflux Reflux
in Glycerol
E709
S
N
Reflux
in Glycerol
3
Ir
S
N
If we can guess the pathway…
O O
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Possible impurity reaction
E709
CH3
CH3
O
OH
-
C5H7O2S
N
C13H8NS
OH
OH
OH
-
Glycerol : C3H7O3
Possible Impurity Reaction
Search
by software
IrCl3O
O
Ir
3
S
N S
N
Ir
CH3
CH3
O
O
2
OLED material : E709
Reflux Reflux
in Glycerol
E709
O O
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Possible impurity reaction
Main component E709
S
N
C13H8NS
Possible Impurity Reaction
S
N
C13H8NSCH3
CH3
O
OH
C5H7O2
+ = +C8HNS-O2-
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Possible impurity reaction
Main component E709
CH3
CH3
O
OH
C5H7O2
S
N
C13H8NS
Possible Impurity Reaction
S
N
C13H8NS CH3
CH3
O
OH
C5H7O2
= -C8HNS+O2
S
N
C13H8NSCH3
CH3
O
OH
C5H7O2
+ = +C8HNS-O2
-
-
+
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Possible impurity reaction
Main component E709
CH3
CH3
O
OH
C5H7O2
S
N
C13H8NS
OH
OH
OH
C3H7O3
Possible Impurity Reaction
S
N
C13H8NS CH3
CH3
O
OH
C5H7O2
= -C8HNS+O2
OH
OH
OH
C3H7O3
S
N
C13H8NSCH3
CH3
O
OH
C5H7O2
+ = +C8HNS-O2
+
-
-
-H+
CH3 CH3
O O
OH
OH
OH
CH3 OH
O OOH
OH
= +C3H6O3
+
Aldol reaction
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Import transformations into the Library
E709
S
N
C13H8NSS
N
C13H8NSCH3
CH3
O
OH
C5H7O2
+ = +C8HNS-O2-
Register transformation in the “Science Library”
Formula
Mass
Type reaction formula
Auto calculation of MW
Register in the “Science Library”
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Import candidate structures into the Library
Main component E709
CH3
CH3
O
OH
C5H7O2
S
N
C13H8NS
OH
OH
OH
C3H7O3
Possible Impurity Reaction
Import
Elucidation
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Impurities from synthetic pathway
Select transformation in processing method
Process
Name Formula m/z RT
Inte
nsity (
count)
Retention (min)
Inte
nsity (
count)
Inte
nsity (
count)
Retention (min) Retention (min)
Name Da Formula
Most confidence
in fragment match
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E709 & impurities
E709 Imp 01 Imp 02 Imp 03
Imp 04 Imp 05 Imp 06
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E709 & impurities
Component RTFormula
(molecule)Monoisotopic
(Da)m/z(M+H) Area Area(%)
E709 4.12 C31H23IrN2O2S2 717.0830 713.0903 21,905,264.00* 98.815
Imp 01 2.95 C31H23IrN2O3S2 728.0779 729.0852 161,026.31 0.726
Imp 02 2.52 C34H29IrN2O5S2 802.1147 803.1220 9,261.18 0.042
Imp 02 2.69 C34H29IrN2O5S2 802.1147 803.1220 32,300.84 0.146
Imp 03 2.63 C32H25IrN2O4S2 758.0885 759.0958 1,524.69 0.007
Imp 03 2.79 C32H25IrN2O4S2 758.0885 759.0958 6,420.56 0.029
Imp 04 3.87 C26H16N2S2 420.0755 421.0828 22,879.06 0.103
Imp 05 3.36 C23H22IrNO4S 601.0899 602.0972 1,105.40 0.005
Imp 06 4.64 C39H24IrN3S3 823.0762 824.0834 28,235.01 0.127
* E709 area is converted from low concentration sample
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Conclusion
Ch1.
Low Energy
Ch2.
High Energy
Quadrupole Collision Tof MS
High resolution MS and data acquisition mode
–Not only accuracy and resolution, also sensitivity is important for impurity profiling
o 0.001% impurity in material → 1000ppm(material/solvent) → 10 ppb (impurity/solvent)
–MSE mode that can provide all precursor & fragment ion spectra with a single injection is
supportive for finding and elucidating impurity peaks
Process software : UNIFI
– A single platform software
– Effectively picking up impurity peak using same fragment, binary compare
and transformation in synthetic pathway.
– Elemental composition → Database search → Fragment match
(in-silico fragmentation) with one click
– Flexible function of science library
Impurity in chemical materials
– Leads to degradation & shorten lifetime of device even at extremely low conc.
–Reducing defective product and improving yields & safety by controlling impurity.