impurity profiling of oled material using uplc qtof...oled material and data acquisition for...

Impurity Profiling of OLED Material Using UPLC/Q-Tof

Waters

Introduction

3 © 2020 Waters Corporation

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


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)


▪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


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


MSE acquisition mode

Ch1.

Low Energy

Ch2.

High Energy

Quadrupole Collision Tof MS

Low

Energy

High

Energy

Time


Spectrum alignment

RT

Ch1.

Low Energy

Ch2.

High Energy

RT

RT

RT

m/z

m/z

Align by peak top time


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



RT

Peak

Compound


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



RT

Peak

Compound


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


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+)


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


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


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


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


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



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



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


Elemental composition of impurity

Elemental composition of precursor ion

– Use precursor ion spectrum in low energy data

Theoretical

MeasuredImpurity Formula

= C31H23IrN2O3S2


Candidate structure of impurity with common fragment

??

C31H23IrN2O2S2

E709

C26H16IrN2S2

C31H23IrN2O3S2

Imp

C26H16IrN2S2

Common fragment

MSMS

MSMS


Candidate structure of impurity with common fragment

??

C31H23IrN2O2S2

E709

C26H16IrN2S2

C31H23IrN2O3S2

Imp

C26H16IrN2S2

?

=

C5H7O2

-

? ?- =

C5H7O3

Common fragment

MSMS

MSMS

Candidate

Import

Library


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

&


Ex) Impurity with common fragment

Ex 2) Extraction by comparison with blank sample

Blank

Sample


Binary compare


#1

#2

#3

#4

#5

#6

#7


#1

#2

#3

#4

#5

#6

#7


#1

#2 2.94 729.0851 150,348

#3

#4

#5 4.72 308.2478 99,002

#6

#7


#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


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


Discover tool for elucidation

Elucidate

Formula

DB

Search

Fragment

match

Elemental

composition

Database

search

Fragment

match

Low confidenceC26H16N2S2


Structural elucidation

Not assigned fragments



Neutral loss = Precursor - fragment

= C26H16N2S2 - C21H11NS2

= C5H5N

Elemental composition

C21H11NS2

Not assigned fragments

N

Impurity may include

this functional group



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


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


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



Main component E709

S

N

C13H8NS


S

N

C13H8NSCH3

CH3

O

OH

C5H7O2

+ = +C8HNS-O2-



Main component E709

CH3

CH3

O

OH

C5H7O2

S

N

C13H8NS


S

N

C13H8NS CH3

CH3

O

OH

C5H7O2

= -C8HNS+O2

S

N

C13H8NSCH3

CH3

O

OH

C5H7O2

+ = +C8HNS-O2

-

-

+



Main component E709

CH3

CH3

O

OH

C5H7O2

S

N

C13H8NS

OH

OH

OH

C3H7O3


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


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”


Import candidate structures into the Library

Main component E709

CH3

CH3

O

OH

C5H7O2

S

N

C13H8NS

OH

OH

OH

C3H7O3


Import

Elucidation


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


E709 & impurities

E709 Imp 01 Imp 02 Imp 03

Imp 04 Imp 05 Imp 06


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


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.

impurity profiling of oled material using uplc qtof...oled material and data acquisition for...

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