Carbohydrate Analysis: Column Chemistries and Detection

Carbohydrate Analysis:
Column Chemistries and Detection
Joe Romano
Waters Corporation
Carbohydrates in Feeds Methodology Forum
AOAC 2007 Annual Meeting
Anaheim, CA
September 18, 2007
©2007 Waters Corporation
Separation Modes for Carbohydrate
Analysis
ƒ Reversed Phase
ƒ Partition or Normal Phase
ƒ Size Exclusion
ƒ Ion Exclusion and Size Exclusion Combined
ƒ Ligand Exchange and Size Exclusion Combined
©2007 Waters Corporation
2
Detectors for Carbohydrate
Analysis
ƒ Refractive Index Detection
ƒ Evaporative Light Scattering Detection (ELSD)
ƒ Pulsed Amperometric Detection (PAD)
©2007 Waters Corporation
3
Separation Modes for
Carbohydrate Analysis
ƒ Reversed Phase
ƒ Partition or Normal Phase
ƒ Size Exclusion
ƒ Ion Exclusion and Size Exclusion Combined
ƒ Ligand Exchange and Size Exclusion Combined
©2007 Waters Corporation
4
Reversed Phase Separation with Refractive
Index Detection
©2007 Waters Corporation
5
Maltose (Alpha 1-4) Oligomers with
Reversed Phase/ PAD
©2007 Waters Corporation
6
Laminarin (Beta 1-3) Oligomers with
Reversed Phase (Resolve C18)/ ELSD
L4
L5
L6
L3
©2007 Waters Corporation
7
Laminarin (Beta 1-3) Oligomers with
Reversed Phase (Hypercarb)/ ELSD
L2
L3
L4
L5
L6
©2007 Waters Corporation
8
Separation Modes for
Carbohydrate Analysis
ƒ Reversed Phase
ƒ Partition or Normal Phase
ƒ Size Exclusion
ƒ Ion Exclusion and Size Exclusion Combined
ƒ Ligand Exchange and Size Exclusion Combined
©2007 Waters Corporation
9
Food Mono- and Disaccharides:
Normal Phase/ Partition/ HILIC
ƒ Challenge: Trying to resolve carbohydrates of:
— Different MW’s
— Different isomers within a MW
ƒ Options: Column Chemistries
— Base particle: silica or polymer
— Bonded phase: amine, diol, amide, polyamine
— Amine-modified (coated) silica: spermine (SAM 1) or guanidine
carbonate (SAM2), triethylamine
©2007 Waters Corporation
10
Food & Beverage
ƒ Nutritional labeling of food products requires listing of sugar
and total carbohydrate content
ƒ Common sugars defined as:
— Monosaccharides: fructose & glucose
— Disaccharides: sucrose, maltose & lactose
ƒ AOAC LC Methods recommend the use of propyl amine
functional columns for analysis of mono & disaccharides in
food products
ƒ Current AOAC LC Methods (amino-based columns)
— 977.20
— 980.20
— 982.14
— 984.17
— 984.22
Honey
Chocolate
Presweetened cereal
Licorice extracts
Purity of lactose
©2007 Waters Corporation
11
Typical Samples
©2007 Waters Corporation
12
Mono- and Disaccharide Analysis
Partition or HILIC Chromatography
HP Carbohydrate Column, 4.6 mm x 25 cm
80% ACN / 20% Water
1.4 mL/min at 35°C; BP = 680 psi
20 µL
2410 Refractive Index, 40°C, 128X
2.5 g/L Each Sugar
33 µ RI Units
Fructose
Glucose
Sucrose
Maltose
Lactose
2.00
3.00
4.00
5.00
6.00
7.00
8.00
9.00
10.00
11.00
12.00
Minutes
©2007 Waters Corporation
13
Sucralose & Sugars with ELSD
Column: YMC-Pack™ Polyamine II, 4.6X250 mm, PB12505-2546WT @ 35°C
Eluent: 75:25 Acetonitrile / Water
150 LSU
1- Sucralose
2- Fructose
3- Glucose
4- Sucrose
5- Maltose
6- Lactose
Flow Rate: 1.0 ml/min
1
Detection: 2420 ELSD, Heater- 60%, 45 psi, Drift- 43°C, Gain-10
Injection Volume- 50 µl
100 ppm level
2
4
3
5
1.00
3.00
5.00
7.00
Minutes
9.00
6
11.00
©2007 Waters Corporation
14
Effect of Acetonitrile Concentration
on Elution Time
©2007 Waters Corporation
15
Carbohydrates by
Partition Chromatography
Column: Waters Carbohydrate Analysis, 4.6X250 mm @ 35ºC
Eluent:
75% acetonitrile, 25% water ( v/v )
Flow Rate: 1.0 ml/min
Detection: RI ( 2414 ) @ 45ºC
Sensitivity: 4
230 mv
3
Analytes
1- Xylose
2- Arabinose
3- Fructose
4- Mannose
5- Glucose
6- Galactose
7*- Maltose
Cellobiose
* coelutions
5
1
5.00
6.00
6
4
2
7.00
8.00
9.00
10.00
g/100mL
0.915
1.16
0.517
0.757
0.441
0.793
0.665
0.775
11.00
12.00
7
13.00
14.00
15.00
Minutes
©2007 Waters Corporation
16
Separation Modes for
Carbohydrate Analysis
ƒ Reversed Phase
ƒ Partition or Normal Phase
ƒ Size Exclusion (Polymers)
ƒ Ion Exclusion and Size Exclusion Combined
ƒ Ligand Exchange and Size Exclusion Combined
ƒ Anion Exchange
©2007 Waters Corporation
17
Ethanol Fermentation Analysis
Using Breeze™ HPLC System
Analytes
g/100 mL
1 Dextrin
0.71
11 2 Maltotriose
0.25
3 Maltose
0.55
4 Dextrose
0.97
5 Fructose
0.24
6 Succinic Acid
0.28
7 Lactic Acid
0.83
8 Glycerol
1.11
9 Acetic Acid
0.40
10 Methanol
1.19
11 Ethanol
11.85
12 2-Propanol
0.75
* Unknowns
Column:
Waters Ion Exclusion
7.8 x 300 mm @ 50ºC
Eluent:
2 mM Sulfuric Acid
Flow Rate: 0.6 mL/min
Detection: RI ( 2414 ) @ 45ºC
Sensitivity: 4
200 m V
4
8
3
1
2
7
5
12
6
9
10
**
0.00
4.00
8.00
12.00
16.00
Minutes
20.00
24.00
28.00
©2007 Waters Corporation
18
Ethanol Fermentation Analytes
Current Analytes
Biomass Analytes
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.
15.
16.
Dextrin (>DP4)
Maltotriose
Maltose (alpha 1-4)
Glucose (dextrose)
Fructose
Glycerol
Propanol
Ethanol
Methanol
Lactic Acid
Succinic Acid
Acetic Acid
Dextrin (>DP4)
Maltotriose
Maltose (alpha 1-4)
Cellobiose (beta 1-4)
Glucose (dextrose)
Fructose
Galactose
Mannose
Arabinose
Xylose
Glycerol
Ethanol
Methanol
Lactic Acid
Succinic Acid
Acetic Acid
©2007 Waters Corporation
19
16 Biomass Carbohydrates by Ion
Exclusion/ SEC
Column:
Waters Ion Exclusion
7.8 x 300 mm @ 50ºC
Eluent:
10 mN Phosphoric Acid
Flow Rate: 0.6 mL/min
Detection: RI ( 2414 ) @ 45ºC
Sensitivity: 4
2
400 mv
5
6
1
Analytes
g/100mL
1- Maltotetraeose ( DP4 )
2- Maltotriose- (DP-3)
3*- Maltose-0.50, Cellobiose
4- Glucose
5*- Fructose- 0.55, Galactose
Mannose 0.52, Xylose
6- Arabinose
7- Succinic Acid
8- Lactic Acid
9- Glycerol
10- Acetic Acid
12
11- Methanol
12- Ethanol
0.13
0.12
0.53
0.58
0.67
0.57
0.12
0.45
0.47
0.58
0.44
0.58
7.89
*- coeluting species
3
4
7
7.00
9.00
11.00
13.00
9
8
15.00
10
17.00
Minutes
11
19.00
21.00
23.00
25.00
©2007 Waters Corporation
20
Separation Modes for
Carbohydrate Analysis
ƒ Reversed Phase
ƒ Partition or Normal Phase
ƒ Size Exclusion (Polymers)
ƒ Ion Exclusion and Size Exclusion Combined
ƒ Ligand Exchange and Size Exclusion Combined
©2007 Waters Corporation
21
Ligand Exchange and
Size Exclusion Combined
ƒ Cation exchange columns
ƒ Separation based first on size exclusion mode (largest
carbohydrate elutes first from column)
ƒ Separation based second on ligand exchange mode
(interaction between hydroxyls and metal counter ions)
— Ca++ and Pb++ (strongest separation)
— Na+ (weaker separations)
©2007 Waters Corporation
22
Explaination of Ligand Exchange Mode
©2007 Waters Corporation
23
Separation of Anomers
Ca 2+ Ligand Exchange/ SEC Column
Columns must be run at temperatures between 70 and 90º C
Anomers Not
Separated
Anomers
Separated
©2007 Waters Corporation
24
Effect of Temperature
Ca 2+ Ligand Exchange/ SEC Column
©2007 Waters Corporation
25
Comparison of Ligand Exchange/SEC
Columns with Different Counter Ions
Na+
Ca2+
Pb2+
©2007 Waters Corporation
26
Monosaccharides and Disaccharides
Ca2+ Ligand Exchange/SEC
©2007 Waters Corporation
27
Biomass Carbohydrates by
Ca 2+ Ligand Exchange/ SEC
3
Column: Waters Sugar-Pak™, 6.5X300 mm @ 90ºC
Eluent:
Water containing 50 mg/L CaEDTA
Flow Rate: 0.5 ml/min
Detection: RI ( 2414 ) @ 50ºC
Sensitivity: 16
5
400 mv
1
Analyte
1- Cellobiose
Maltose
2- Glucose
3- Galactose
Xylose
Mannose
4- Fructose
5- Arabinose
g/100mL
0.78
0.665
0.44
0.79
0.91
0.76
0.52
1.16
* coelutions
4
2
6.00 6.50 7.00 7.50 8.00 8.50 9.00 9.50 10.00 10.50 11.00 11.50 12.00 12.50 13.00 13.50 14.00
Minutes
©2007 Waters Corporation
28
Monosaccharides and Disaccharides
Pb 2+ Ligand Exchange/ SEC Column
Slow flow rates: 0.6 ml/min
High Temperature: 80º C
Lead salt in mobile phase
Sample preparation required
Sample: 5micro-L
1.Cellobiose 1.0%
2.Glucose 1.5%
3.Xylose 0.5%
4.Galactose 0.5%
5.Arabinose 0.5%
6.Mannose 1.0%
©2007 Waters Corporation
29
Summary: Separation Modes for
Carbohydrate Analysis
ƒ Reversed Phase
ƒ Partition or Normal Phase
ƒ Size Exclusion (Polymers)
ƒ Ion Exclusion and Size Exclusion Combined
ƒ Ligand Exchange and Size Exclusion Combined
©2007 Waters Corporation
30