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Développement de méthodes en UPC² Développement de méthodes en UPC
Gilles JAOUEN
©2015 Waters Corporation 1
Rappel : principe du CO2 supercritiqueDiagramme de phaseg p
T (⁰C) P (Bar)CO 31 76 CO2 31 76
©2015 Waters Corporation 2
Rappel : La Chromatographie Convergente UPC²g p g
SFC UltraPerformanceConvergence Chromatographyg g p y
UltraPerformance Convergence Chromatography est le résultatd’avancées technologiques significatives dans l’instrumentationSFC et les chimie de colonnes ce qui conduit à une augmentationSFC et les chimie de colonnes ce qui conduit à une augmentation importante de sélectivités accessibles.
Table. Ordre de grandeur de la diffusion, la viscosité et la
Gas Supercritical Fluid
Liquid
3 1
diffusivité
Density (g/cm3)
10-3 10-1-1Liquid-like
1
Diffusivity (cm2/s)
10-1 10-4-10-3 <10-5
Viscosity 10-4 10-4-10-3 10-2
©2015 Waters Corporation 3Data courtesy of Davy Guillarme, Jean-Luc Veuthey LCAP, University of Geneva, Switzerland
Viscosity (g/cm·s)
10 10 10Gas-like
10
Rappel :Fonctionnement de l’ACQUITY UPC2
PDA detector
Splitter
Column ManagerMake-up
Pump
AuxiliaryInject valve
Back Pressure Regulator(Dynamic and Static)
Pump
Mass Spec
Inject valve
mixerThermo-electric heat exchanger
©2015 Waters Corporation 4
Waste Modifier CO2Supply CO2
PumpModifier
Pump
Sélectivité: L’apport de la Chromatographie Convergente
SolventPentane, Hexane,
HeptaneSupercritical
COHeptane
Xylene
Toluene
Diethyl ether
Wea
k
CO2
Convergence
Dichloromethane
Chloroform
Acetone
Wg
Chromatography Selectivity Space
Dioxane
THF
MTBE
Ethyl acetate
DMSO
Acetonitrile
I l
Str
ong
©2015 Waters Corporation 5
Isopropanol
Ethanol
MethanolOrganicModifier
Développement de méthodes UPC²Mode achiralMode achiral
©2015 Waters Corporation 6
New UPC2 Achiral Phases – Torus™
Highlights– 4 completely new innovative chemistries for UPC2p y
o 1.7 µm particles, 2.1 and 3.0 mm ID– Excellent peak shape – eliminates or reduces need for additives– Added selectivity – wide range of compoundsAdded selectivity wide range of compounds– Improved Robustness
©2015 Waters Corporation 7
Torus Technologygy
A new particle technology Novel two-stage bonding process yielding high density ligands Novel, two stage bonding process yielding high density ligands The second stage imparts the unique selectivity for each phase
– new interactions with analytes
O SiO
OO
OHNH
N
O OH
ACQUITY UPC2
Torus 2-PIC
ACQUITY UPC2
1 7 µm
High Density Bonding
O SiO
OO
OHN
O OH
ACQUITY UPC2
Torus DEA
ACQUITY UPC2 1.7 µm BEH Particle
O SiO
OOH
NH
O SiO
O OH ACQUITY UPCTorus DIOL
ACQUITY UPC2
Torus 1-AA
©2015 Waters Corporation 8
US 6,686,035US 7,223,473Others patent pending
OTorus 1-AA
Wide Range of SelectivityGreater S-Value, Greater Orthogonality, g y
1
3 2
568
S-Value Reference
1
2 35
4 72-PIC
S-Value = 584 6
78DEA
3 25
6 8
1 47
DIOL
S-Value = 93
1
3
24
56
7
8
S-Value = 90
©2015 Waters Corporation 9
Minutes0.00 0.50 1.00 1.50 2.00 2.50 3.00 3.50 4.00 4.50 5.00
1-AA
(1) Uwe Neue, et al. , Journal of Chromatography A, 1127 (2006
Wide Range of SelectivityGreater S-Value, Greater Orthogonality, g y
1
3 2
568
S-Value Reference
1
2 35
4 72-PIC
S-Value = 584 6
78DEA
3 25
6 8
1 47
DIOL
S-Value = 93
1
3
24
56
7
8
S-Value = 90
©2015 Waters Corporation 10
Minutes0.00 0.50 1.00 1.50 2.00 2.50 3.00 3.50 4.00 4.50 5.00
1-AA
(1) Uwe Neue, et al. , Journal of Chromatography A, 1127 (2006
Better Peak Shape Without Additives – Torus 2-PIC
1. Ibuprofen2. Theophylline3. Amitriptyline4. Fenoprofen5. Thymine6 P l l
3.0 x 50mm, 1.2mL/min, 5-40% MeOH in four min, 40C, 2175psi
86. Propranolol7. Prednisolone8. Sulfamethoxazole9. Cytosine
Conventional 2-EP 1 7µm3
2 5
61 7
4
9Conventional 2 EP 1.7µm
6
ACQUITY UPC² Torus 2-PIC 1.7µm
12
3 45
7 89
Minutes0.00 0.55 1.10 1.65 2.20 2.75 3.30 3.85 4.40 4.95 5.50
©2015 Waters Corporation 11
Excellent peak shapes seen on 2-PIC using pure MeOH co-solvent
Torus 2-PICEffect of Basic Additive
1
5
37 3.0 x 100mm
1.5mL/min10% Co-Solvent2500psi
1.Caffiene2.Papaverine3.Amitriptyline4 Fenoprofen4
5
2
6
8
35C4.Fenoprofen5.Thymine6.Prednisone7.Propranolol8.Prednisolone9.Sulfamethoxazole10 Sulfanilamide MeOH6
9
10
10.Sulfanilamide
3
MeOH
1
37
45
2 8 MeOHw/ 40mM NH3
©2015 Waters Corporation 12Minutes0.00 2.00 4.00 6.00 8.00 10.00 12.00 14.00 16.00 18.00 20.00
69
10
w/ 40mM NH3
Torus DEA – Good Peak Shapes for Strong Basesg
1 7 T DEA
Column: 3.0 x 100 mmFlow rate: 1.5 mL/min IsocraticMobile Phase: 12% MeOHTemperature: 35°CABPR: 2500 psi
Competitor 1 8µm 2-EP
1.7µm Torus DEA ABPR: 2500 psi
Competitor 1.8µm 2 EPTrimipramineAmitriptylineImipramineNortriptyline
Minutes0.0 0.5 1.0 1.5 2.0 2.5 Minutes0.0 0.5 1.0 1.5 2.0 2.5
No additive needed to give sharp peak shapes for very basic compounds – necessary to take advantage of rapid UPC2
©2015 Waters Corporation 13
compounds necessary to take advantage of rapid UPCseparations
Torus DIOL– Good Peak Shapes for Acidic Analytesy
4.2e-1
4.4e-1
4.6e-1
4.8e-1
3.0e-1
3.2e-1
3.4e-1
3.6e-1
3.8e-1
4.0e-1
AU
1 6e-1
1.8e-1
2.0e-1
2.2e-1
2.4e-1
2.6e-1
2.8e-1
P iti l I f
4.0e-2
6.0e-2
8.0e-2
1.0e-1
1.2e-1
1.4e-1
1.6e 1 Positional Isomers of Dimethoxybenzoic Acids
Excellent peak shape for a three minute separation of acidic aromatic regioisomers
Time-0.00 0.10 0.20 0.30 0.40 0.50 0.60 0.70 0.80 0.90 1.00 1.10 1.20 1.30 1.40 1.50 1.60 1.70 1.80 1.90 2.00 2.10 2.20 2.30 2.40 2.50 2.60 2.70 2.80 2.90 3.00 3.10 3.20 3.30
0.0
2.0e-2
©2015 Waters Corporation 14
Technology Brief: “Direct separations of the six positional isomers of disubstituted benzoic acids using ACQUITY UPC2 Torus columns”
Torus 1Torus 1--AA for Hydrophobic CompoundsAA for Hydrophobic CompoundsFree Fatty AcidsFree Fatty Acidsyy
Time (min) Flow (mL/min) %B Curve
Initial 1.9 1.8 --
5.0 1.9 11 9
3.0x100mm 1.7µm Torus 1-AACO2/MeOH, 50C, 2100psi BPRUPC2 w/ QDa ESI-
C16:1
C16
C20:4
5.5 1.9 30 1
6.5 1.9 30 11
7.0 1.9 1.8 1
UPC w/ QDa ESI
C17
C17:1 C18:2
C20:2
C20:4
C22:2
Carbon length : number of double bonds
% C14C14:1
C15C15:1
C17 C18
C20 C22C20:1 C22:1 C22:6
C24:1
C10C11 C12
C13
©2015 Waters Corporation 15
Time (min)0.60 1.00 1.40 1.80 2.20 2.60 3.00 3.40 3.80 4.20 4.60 5.00
0
C6 C8C10
Method Development Strategy for Achiral ACQUITY UPC² Torus ColumnsQ
2) Defined Screening1) Rapid Scouting 3) Optimization
Acidic orMix Analyte
) gGeneric gradient with specified chemistry
and co-solvent
DIOL DIOL w/baseGeneric Gradient:
1.2 mL/min,
2-PIC
Co-solvent
BasicAnalytes DEA DEA
w/base
4-50% MeOH in 3 mins30°C, 2,000 psi
3.0 x 100 mm column
A) If separation criteria is met then proceed to
Temperature
Order of im
p
1-AA /b
/
1-AA / id
NeutralAnalytes
met, then proceed to Optimization if needed
B) If good separation but need better peak shape, then run 2-PIC
Additive
Backpressure
pact
w/base w/acidAnalytesp ,with additive
C) If different separation is needed, proceed to Defined Screening
Backpressure
©2015 Waters Corporation 16
ACQUITY UPC² Torus Columns Method Development Strategyp gy
2) Defined ScreeningGeneric gradient with specified chemistry
d l t
1) Rapid Scouting 3) Optimization
2 CAcidic or
Mix Analyte
and co-solvent
DIOL DIOL w/baseGeneric Gradient:
1.2 mL/min, 4-50% MeOH in 3 mins
30°C 2 000 psi
2-PIC
Co-solvent
Ord
BasicAnalytes DEA DEA
w/base
30 C, 2,000 psi3.0 x 100 mm column
A) If separation criteria is met, then proceed to Optimization if
Temperature
der of impact
1-AA w/base
1-AA w/acid
NeutralAnalytes
pneeded
B) If good separation but need better peak shape, then run 2-PIC with additive
Additive
Backpressure
t
C) If different separation is needed, proceed to Defined Screening
©2015 Waters Corporation 17
ACQUITY UPC² Torus Columns Method Development Strategyp gy
2) Defined ScreeningGeneric gradient with specified chemistry
d l t
1) Rapid Scouting 3) Optimization
2 CAcidic or
Mix Analyte
and co-solvent
DIOL DIOL w/baseGeneric Gradient:
1.2 mL/min, 4-50% MeOH in 3 mins
30°C 2 000 psi
2-PIC
Co-solvent
Ord
BasicAnalytes DEA DEA
w/base
30 C, 2,000 psi3.0 x 100 mm column
A) If separation criteria is met, then proceed to Optimization if
Temperature
der of impact
1-AA w/base
1-AA w/acid
NeutralAnalytes
pneeded
B) If good separation but need better peak shape, then run 2-PIC with additive
Additive
Backpressure
t
C) If different separation is needed, proceed to Defined Screening
©2015 Waters Corporation 18
Simplified Column Selectionp
Torus Columns will use a targeted screening approach to method development. The goal is to minimize the effort needed to arrive at a set of conditions that can be optimized
©2015 Waters Corporation 19
to arrive at a set of conditions that can be optimized.
Développement de méthodes UPC²Phases chiralesPhases chirales
©2015 Waters Corporation 20
Chiral Stationary Phase (CSP)Structures
O
OR
O
HN
R
O
RO
OR
n
OR=
AMY1: Amylose tris-(3,5-dimethylphenylcarbamate)
OO
OR
RO
HN
R=Chiral polysaccharide coating on silica particle
“Chiral Selector” modulatesthe chiral recognition
RO
OR
n
O
CEL1: Cellulose tris-(3,5-dimethylphenylcarbamate)
coat g o s ca pa t c ecreates the chiralenvironment
OO
OR
RO
Cl
HN
R=
©2015 Waters Corporation 21
RO
OR
n
OR
CEL2: Cellulose tris-(3-chloro-4-methylphenylcarbamate)
Trefoil™ Columns CoverA Wide Range of Selectivities
AMY1 CEL1 CEL2
g
Troger’s Base
B i i iBupivicaine
O
O
Minutes0.00 0.80 1.60 2.40 3.20 4.00
Minutes0.00 0.60 1.20 1.80 2.40 3.00
Minutes0.00 0.80 1.60 2.40 3.20 4.00Trimebutine
O
O
ON
©2015 Waters Corporation 22
UPC2 Chiral Method Development (MD)Key Success Elementsy
ACQUITY UPC2 Best analytical SFC
f l CS Trefoil™ CSPs: – Trefoil™ AMY1– Trefoil™ CEL1 Highest chiral separation success– Trefoil™ CEL2
2.5 um particles Best in class efficiency vs. 3.0 & 5.0 um 2.1 x 50 mm Max. speed / Min. solvent use
Method– 2 min Screening Method Ballistic general purpose gradient
o PDA/MS detection Peak identification/confirmation
Optimal Combinations of co-solvents & additives favorably modulate chiral recognition
©2015 Waters Corporation 23
Quicker Method Development Success
SFC Chiral MD Study:Co-Solvent / Additive CombinationImpact on Chiral Resolution SuccessImpact on Chiral Resolution SuccessSystematic Variation of Co-Solvents & Additives 15 Combinations of 4 Co-Solvents:
Condition MeOH EtOH IPA ACN Low pH Mid pH High pH1 X X2 X X3 X X
– Methanol, Ethanol, Isopropanol, Acetonitrile
3 Additives (Low, Mid & High pH)
4 X X5 X X6 X X7 X X8 X X9 X X10 X X11 ‐‐‐ ‐‐‐12 X X13 X X X14 X X X
Single Co-Solvents X 3 Additives
– Trifluroacetic Acid (TFA), Ammonium Acetate (AmAc), Ammonium Hydroxide (AmOH)
14 X X X15 X X X16 X X X17 X X X18 X X X19 X X X20 X X X21 X X X22 X X X23 X X X24 X X X25 X X X
Binary Co-Solvent Blends X 3 Additives
25 X X X26 X X X27 X X X28 X X X29 X X X30 X X X31 X X X X32 X X X X33 X X X X34 X X X X35 X X X X
For 1 CSP:44 combinations x 55 chiral study 36 X X X X
37 X X X X38 X X X X39 X X X X40 X X X X41 X X X X42 X X X X43 X X X X X44 X X X X X45 X X X X X
Ternary Co-Solvent Blends X 3 Additives
Quaternary Co-Solvent Blends X 3 Additives
x 55 chiral study compounds=2,420 runs
©2015 Waters Corporation 24
Examined 44 Co-Solvent / Additive Combinations(excluded ACN with Ammonium Acetate (AmAc) due to insolubility)
SFC Chiral MD Study:Search for Optimal CombinationsWith Trefoil™ AMY1 ColumnWith Trefoil™ AMY1 Column
UPC2™ chromatography of 55 representative chiral compounds. Each racemate is problem needing a solution (resolution!!!) Each racemate is problem needing a solution (resolution!!!). Examine 2,420 separate analyses (UV and MS ESI +/- per analysis)
using this “Pass” criterion:– Enantiomer Resolution If Rs > 1.2 then compound solved!
©2015 Waters Corporation 25
Selectivity (50 mm AMY1 screen column)Modulation Example
0 32
p
N
NH
O
SH2N
O
O
AU
0.000.080.160.240.32 H
O
O
Methanol/IsopropanolAmmonium HydroxideRs = 0.74
Sulpiride
AU
0.080.160.240.32
Isopropanol/AcetonitrileAmmonium HydroxideRs = 0.27
0.00
AU
0 150.300.450.60 Ethanol/Acetonitrile
Ammonium AcetateRs = 0.73
0.000.15
AU 0 40
0.600.80 Ethanol/Isopropanol
TFA
©2015 Waters Corporation 26
A
0.000.200.40
Minutes0.00 0.40 0.80 1.20 1.60 2.00
Rs = 1.47
SFC Chiral MD Study:Search for Optimal CombinationsWith Trefoil™ AMY1 Column (cont )With Trefoil™ AMY1 Column (cont.)
Found:– 34 Chiral compounds were “solved” by at least one combination.34 Chiral compounds were solved by at least one combination.
“Optimal Combination” (def.):– A combination of Co-Solvents / Additives associated with
high chiral resolution successhigh chiral resolution success.
Ask:– What is the fewest number of Optimal Combinations needed to solve
h “ i i l h”these compounds? The “Critical Path”.
©2015 Waters Corporation 27
AMY1 Critical Path Through “Co-Solvents / Additive Space”pStep Combo % Salvage % Total Success
1 EtOH / ACN / AmAc ---- 56 %
2 EtOH / IPA / TFA 18 % 74 %
3 IPA / ACN / AmOH 14 % 88 %
4 MeOH / IPA / AmOH 6 % 94 %/ /
5 IPA / AmOH 3 % 97 %
6 ACN / TFA 3 % 100 %
90.0%100.0%
ss
% Success by Step
50.0%60.0%70.0%80.0%
Total Succe
All CombosHigh success rate can be achieved High success rate can be achieved with 4 cowith 4 co--solvent / additive combossolvent / additive combos
©2015 Waters Corporation 28
40.0%1 2 3 4 5 6
Step
What if we had only used single co-solvents?gStep Combo % Salvage % Total Success
1 EtOH / AmOH ---- 44%
2 IPA / TFA 18 % 62%
3 EtOH / TFA 6 % 68%
4 ACN / TFA 6 % 74%/
5 MeOH / AmOH 3 % 77%
6 IPA / AmAc 2 % 79%
90.0%100.0%
ess
% Success by Step
50.0%60.0%70.0%80.0%
Total Succe
All Combos
Single CombosSingle coSingle co--solvents solvents are inferior to coare inferior to co--solvent blendssolvent blends
©2015 Waters Corporation 29
40.0%1 2 3 4 5 6
Step
are inferior to coare inferior to co solvent blendssolvent blends
Full 3 CSP Method DevelopmentStrategy: AMY1, CEL1, CEL2gy , ,
Expand to 3 CSP’s: AMY1, CEL1, CEL2– Examine 4 Step efficiency for each CSP (2,420 x 3 = 7260 analyses).Examine 4 Step efficiency for each CSP (2,420 x 3 7260 analyses).– Examine 4 Step efficiency for full compound set (55).– Explore most efficient CSP/co-solvent/additive “Critical Path”.
G l 4 t 8 i t Chi l M th d –Goal: 4 step, 8 minute Chiral Method Development. AMY1 CEL1 CEL2
Condition MeOH EtOH IPA ACN Low pH Mid pH High pH1 X X2 X X
Condition MeOH EtOH IPA ACN Low pH Mid pH High pH1 X X2 X X
Condition MeOH EtOH IPA ACN Low pH Mid pH High pH1 X X2 X X
For 3 CSP:44 combinations x 55 compounds
X X3 X X4 X X5 X X6 X X7 X X8 X X9 X X10 X X11 ‐‐‐ ‐‐‐12 X X13 X X X14 X X X15 X X X16 X X X17 X X X18 X X X19 X X X20 X X X21 X X X22 X X X
X X3 X X4 X X5 X X6 X X7 X X8 X X9 X X10 X X11 ‐‐‐ ‐‐‐12 X X13 X X X14 X X X15 X X X16 X X X17 X X X18 X X X19 X X X20 X X X21 X X X22 X X X
X X3 X X4 X X5 X X6 X X7 X X8 X X9 X X10 X X11 ‐‐‐ ‐‐‐12 X X13 X X X14 X X X15 X X X16 X X X17 X X X18 X X X19 X X X20 X X X21 X X X22 X X Xx 55 compounds
x 3 CSPs=7,260 runs
23 X X X24 X X X25 X X X26 X X X27 X X X28 X X X29 X X X30 X X X31 X X X X32 X X X X33 X X X X34 X X X X35 X X X X36 X X X X37 X X X X38 X X X X39 X X X X40 X X X X41 X X X X42 X X X X43 X X X X X
23 X X X24 X X X25 X X X26 X X X27 X X X28 X X X29 X X X30 X X X31 X X X X32 X X X X33 X X X X34 X X X X35 X X X X36 X X X X37 X X X X38 X X X X39 X X X X40 X X X X41 X X X X42 X X X X43 X X X X X
23 X X X24 X X X25 X X X26 X X X27 X X X28 X X X29 X X X30 X X X31 X X X X32 X X X X33 X X X X34 X X X X35 X X X X36 X X X X37 X X X X38 X X X X39 X X X X40 X X X X41 X X X X42 X X X X43 X X X X X
©2015 Waters Corporation 30
43 X X X X X44 X X X X X45 X X X X X
43 X X X X X44 X X X X X45 X X X X X
43 X X X X X44 X X X X X45 X X X X X
AMY1 + CEL1 + CEL2Optimal Path ScreenUsing All Combos
Step Combo % Salvage % Total Success
1 AMY1 EtOH/IPA/ACN AmAc 45 5 %1 AMY1-EtOH/IPA/ACN-AmAc ---- 45.5 %
2 CEL1-MeOH/IPA-TFA 27.3 % 72.7 %
3 CEL2-EtOH/ACN-TFA 13.6 % 86.4 %
4 AMY1-EtOH/IPA-TFA 9.1 % 95.5 %
5 CEL1-IPA-TFA 4.5 % 100.0%
80.0%90.0%100.0%
ess
% Success by Step
40.0%50.0%60.0%70.0%80.0%
Total Succe
All Combos
©2015 Waters Corporation 31
30.0%1 2 3 4 5 6
Step
AMY1 + CEL1 + CEL2 Optimal Path Screen Using Single Co-Solvent Combos
Step Combo % Salvage % Total Success1 CEL1 EtOH TFA 43 2 %1 CEL1-EtOH-TFA ---- 43.2 %2 AMY1-EtOH-AmOH 22.7 % 65.9 %3 CEL2-EtOH-TFA 11.4 % 77.3 %4 AMY1 IPA A A 4 5 % 81 8 %4 AMY1-IPA-AmAc 4.5 % 81.8 %5 AMY1-EtOH-TFA 4.5 % 86.4 %6 CEL1-IPA-TFA 4.5 % 90.9 %
90.0%100.0%
s
% Success by Step AMY1+CEL1+CEL2: Recommend Co-Solvent
Mixtures
40.0%50.0%60.0%70.0%80.0%
Total Success
All Combos
Single Combos
For 3 CSPs, CoFor 3 CSPs, Co--Solvent Solvent mixturesmixtures are are better than single Cobetter than single Co--Solvents (ca. 14%)Solvents (ca. 14%)
©2015 Waters Corporation 32
30.0%1 2 3 4 5 6
Step
Trefoil™ Chiral Method Development:Strategy DetailsS a egy e a s
Use all three 2.1x50mm Trefoil columns and the ballistic screening method on ACQUITY UPC² to implement the following screening method on ACQUITY UPC to implement the following Trefoil Optimal Path Screen (4 steps):
S l 2 Minute Screening MethodStep Columns & Blends Solv
Line1 AMY1-EtOH/IPA/ACN-AmAc B1
2 Minute Screening MethodTrefoil 2.1x50 mm columns @ 40°C 1.2 mL/min flow rate ABPR = 3200 psi
Use indicated blend with:
2 CEL1-MeOH/IPA-TFA B23 CEL2-EtOH/ACN-TFA B34 AMY1 EtOH/IPA TFA B4
Use d cated b e d t• 20 mM AmAc OR • 0.2% TFA
Equilibrate: 3% B for 0.5 minGradient: 3 to 60% B over 1.5 min 4 AMY1-EtOH/IPA-TFA B4 Hold: 60% B for 0.5 min
2.5 min Cycle Time per Step
©2015 Waters Corporation 33
ACQUITY UPCACQUITY UPC22 Trefoil Columns Trefoil Columns for for ChiralChiral SeparationsSeparationspp
Highlights– Designed for the ACQUITY UPC2 Systemg Q y
o Transition away from Normal Phase LC– Broad selectivity for separation of a wide range of chiral
compounds– High speed and efficiency
o Fast gradients - 2.5 µm particles, 2.1 and 3.0 mm ID– Excellent mechanical stability– Mass spectrometer compatible
o Single Quad for Method developmento Triple Quad for DMPK studiesp Qo Tof for accurate mass, impurity ID
Chiral & Achiral analysis using same mobile phases and same t
©2015 Waters Corporation 34
system
Conclusion
L’UPC² a démontré ses bénéfices en tant que:– Technique complémentaire à la LC (sélectivité très différente)– Alternative à la phase normale– Technique simple d’utilisation et avec une bonne performance– Système à coût réduit d’utilisation
L’UPC² s’applique à un nombre important de domaines:– Séparations chirales– Chimie de synthèse– Produits finis dans le pharmaceutique par exemple– Industrie chimique (tensio-actifs, composés apolaires…)– Les lipides
b d’– Et bien d’autres… Flexibilité de la détection
– Optique : UV, PDA, Fluo, DEDLMS l W
©2015 Waters Corporation 35
– MS : toute la gamme Waters