Universal detection see what others miss consistent • sensitive • versatile

Thermo Scientific Dionex Corona ultra RS Charged Aerosol Detector

The Problem—Detection

No HPLC or UHPLC detector is perfect. UV detection is the most

widely used technique, but it fails to detect compounds without

chromophores. Other universal detectors do not combine application

versatility with reliability. This results in detection gaps.

The Solution

The Thermo Scientific™ Dionex™ Corona™ ultra RS™ Charged

Aerosol Detector is the solution. Charged aerosol detection delivers

performance that refractive index (RI), low-wavelength UV, and

evaporative light scattering (ELS) detectors simply cannot match. It

measures analytes that other technologies fail to detect. Charged

aerosol detection has greater sensitivity, wider dynamic range, and

more consistent response. Virtually every pharmaceutical company

has adopted charged aerosol detection.

The Corona ultra RS detector goes beyond simple HPLC. It

combines all the benefits of charged aerosol detection with the high

speed and increased resolution of UHPLC.

Comparison of Charged Aerosol Detection to UV and MS

Minutes0 0.5 1 1.5 2

Void + Cl-Propanolol

Ketoprofen Verapamil

UV at 220 nm

UV at 254 nm

Charged Aerosol Detection

MS TIC(+ ion scan 150-500AMU)

The Corona ultra RS Detector Sees the Complete Picture

The Corona ultra RS detector can be used with the

most up-to-date UHPLC technology to measure

analytes that cannot be seen by UV and may not

be readily detected by mass spectrometry.

With the flexibility and performance for analytical

R&D, and the simplicity and reproducibility needed

for manufacturing QC/QA, the Corona ultra RS

detector can be used for the analysis of

pharmaceuticals (large and small molecule),

biofuels, foods and beverages, specialty chemicals,

and counterions. The detector can also be used in

a range of applications from basic research to

quality control.

Corona ultra RS Detector Benefits

• Consistent response independent of chemical structure

• Compatibility with UHPLC

• Simple and easy to use

2

Going beyond HPLC

Charged Aerosol Detection

What makes any detector useful is its ability to accurately measure

a wide range of analytes with consistent response. However, most

detectors exhibit limitations. Often, one analyte responds more

strongly than another, or may not respond at all.

The Corona ultra RS detector measures charge that is imparted to

analyte particles, with the charge being in direct proportion to the

amount of the analyte in the sample. Measuring this charge is

Step Two

A stream of positively charged

gas collides with the analyte

particles. The charge is then

transferred to the particles–the

larger the particles, the greater

the charge.

Step Three

The particles are transferred to a

collector where the charge is

measured by a highly sensitive

electrometer. This generates a

signal in direct proportion to the

quantity of analyte present.

HPLC Column Eluent

Gas Inlet

Nebulizer and Impactor

Signal Out

CollectorAnalyte particles transfer their charge to a sensitive electrometer

Ion Trap

Analyte is nebulized and dried to produce particles

Largest droplets are eliminated

Positive charge is transferred to analyte particles

Positive charge added to gas stream

accurate and consistent, regardless of the analyte.

The result is that the detector can quantify any

nonvolatile analyte—this includes those without

chromophores or those that cannot ionize—thus

providing a consistent response that is indepen-

dent of chemical structure. With charged aerosol

detection, you can even measure many

semivolatile analytes.

3

Going beyond HPLC

Simplicity in Operation

Step One

Charged aerosol detection

begins by nebulizing the eluent

into droplets, which are

subsequently dried into particles.

The particle size increases with

the amount of analyte.

Consistent Response

The magnitude of response obtained

for nonvolatile analytes using charged

aerosol detection is independent of

chemical structure. This is demonstrated in

the figure to the right, where response by flow

injection analysis is very similar for equivalent

amounts of a wide variety of analytes. The

detector response does not depend on

analyte optical properties as with ultraviolet

(UV) absorbance, or the ability to ionize as

with mass spectrometry (MS). This is critical

for studies dependent on mass balance

assessment or where UV response varies

greatly. The response with charged aerosol

detection is predictable.

Wide Dynamic Range

The Corona ultra RS detector is unique among universal detectors in

that it allows quantitation across a range that exceeds four orders of

magnitude. This wide dynamic range provides significant advantages

for the simultaneous measurement of an analyte and low-level

impurities in a single run. In the forced degradation example shown

below, trace levels of degradant are found at the 0.19% level—well

above the limit of detection. The wide dynamic range means that the

low-level impurity and the active

pharmaceutical ingredient (API) can be

measured in the same run. With response

independent of structure, relative levels can

be assessed even without knowing the

identity of the peak.

Consistent response and a wide dynamic range

Enhanced Performance

4

10.7% RSD variation in CAD responseamong 1.0 µg samples by flow injection

Detector Response for Nonvolatiles

250,000

200,000

150,000

100,000

50,000

0 Warfarin

4 Aminoquinaldine

Papaverine

Gentisic acid

Primidone

Tartaric acid

Glucosamine

Adrenosterone

Cyclodextrin

Dibucaine

Progestrone

Propranolol

Glucose

Lactose

Methionine

Amitriptyline

Glutathione

Umbelliferone

Dextrin

Sucrose

Homocysteine

Fructose

Salicylic acid

NortriptylineAnalyte

DegradantImpurities

Impurities

Amikacin

0 0.5 1 1.5 2 2.5 3 43.5Minutes

140

0

0.4 0.6 0.8

20 minutesheating

10 minutesheating

noheating

mV

600

0

mV

Forced Degradation

Enhanced Sensitivity

The Corona ultra RS detector provides an enhancement in sensitivity

when used with UHPLC. Sub-nanogram levels of detection can be

readily achieved, but there is more than just greater sensitivity. More

importantly, the level of sensitivity is consistent across analyte types.

Complementary to UV and MS Detection

The Corona ultra RS is an ideal primary detector. However, when

combined with UV, diode array detection (DAD), or MS, it provides

an orthogonal and complementary detection mechanism, allowing

you to obtain additional analytical data.

Even More with UHPLC

The high acquisition rate and low-peak dispersion of the Corona

ultra RS detector allows you to exploit the increased separation

speed and resolution of UHPLC, giving results that are 5–10 times

faster than standard HPLC.

When used with the Thermo Scientific Dionex UltiMate™ 3000 RSLC

x2 Dual System employing inverse gradient capability, relative

peak response becomes a practical reality, providing the benefit

of consistent response across the entire gradient range. Now,

you can determine relative purity or level of degradation even

without standards.

Enhanced Performance

5

Achieving New Levels of Sensitivity

Glucose Sucrose Lactose

500 pg of each sugar on column

˜50 ng of each sugar on column

The Corona ultra RS detector incorporates capabilities to make applications easier, including:• An internal valve to send unwanted analytes to waste

• An optional flow splitter for easier interfacing with MS

• A flow diversion system to eliminate waste overfilling

• A unique algorithm for data processing

• All the filter settings of the Corona CAD

Enhanced performance

For Ultimate Performance...

Combine the Corona ultra RS with the UltiMate 3000 x2 pump for cost-effective gradient compensation, providing an ideal tool for approximation of relative concentrations when standards are not available.

Intuitive, simple to operate, and easy to integrate

Ease of Use

The Corona ultra RS detector is virtually plug-and-play. It uses

touchscreen technology that is easy to navigate. There are few

parameters to set, and the few options are displayed on a single

screen. Instrumental parameters are explained on the screen to

allow easy choice of settings. This simple, intuitive operation means

the detector can be quickly installed, enabling you to quickly begin

generating data.

Diagnostics

A diagnostic screen provides all the information necessary to assure

that the detector is working correctly. In addition, values are easy to

interpret. This function provides information to help with instrument

and method validation and troubleshooting. The detector even

prompts you when it is time for preventive maintenance.

Solvent Compatibility and Conservation

Virtually any volatile solvent can be used with the Corona ultra RS

detector without concern for compatibility or UV cutoff. When used

with UHPLC, run times can be reduced by a factor of 5–10 times.

This saves solvent and reduces waste.

Reproducibility and Reliability

Charged aerosol detection is highly reproducible.

The figure below shows the overlay of five runs.

The peak shapes and responses are so

reproducible that it is difficult to distinguish the

individual runs. RSDs of less than 1% are typical.

Data from 150 randomly selected units over a

six-month period show an inter-unit variability of

approximately 2.5%. This means that you can

expect the same results independent of the

location of the detector.

6

Comparison of UHPLC to HPLC

0 10 12.5 15 17.52.5 7.55Minutes

400

0

200

0 4 51 32

400

0

200

HPLCUHPLC

PEG 400Overlay of five injections

Intuitive, simple to operate, and easy to integrate

Easily Integrates with any HPLC System

The Corona ultra RS detector can be used with any standard HPLC

system, but is also ready for UHPLC without any modification.

The detector is designed to integrate into any liquid chromatographic

system, HPLC or UHPLC, from any manufacturer. Software

drivers are available for the Thermo Scientific Dionex

Chromeleon™ Chromatography Data System, as well as

ChemStation®, EZChrom®, and Empower® software. The stackable

design and rugged construction allow it to be placed anywhere in a

system. There is no concern about moving or tipping the detector.

7

Makes Using the System Simple

An on-board switching valve allows flow diversion of

high-salt samples during the analysis to simplify the

chromatogram. The same valve can be used to divert

flow to a different detector without having to

disassemble the system. There is nothing to obtain

separately, nothing that needs to be installed. It is all

built into the detector. An optional variable-ratio flow

splitter is available to integrate with MS or other

parallel detectors without loss of resolution.

0.50.3 1 21.5Minutes

4

0

-0.5

Original chromatogram

Chromatogram with flow diversion

Overlay of multiple injections

pA

2

1

Minutes

0.3 0.90.6 1.51.2

0-.50

3

pA

Flow Diversion

Total Glycerides of Biodiesel

Minutes

550

300

0-50

1-Oleylglycerol

1,3-Diolein MinutesMinutes

28.28 29 29.336.93

9.75

pA56 ng

Triolein

5.95 8.75 9.957.51.4

20.3

pA Glycerol

0 5 10 20 25 30 35 39.415

Minutes

300

mV

0

0 2 4 8 106

1

2

3 4

5

1. Fucose2. Fructose3. Glucose4. Sucrose5. Lactose

Carbohydrates

0 5 10 15 20 25 30 40 45 50 55 60 65 72.735

Minutes

180

-5

Fatty Alcohols

Fatty Acids

Monoglycerides

Steroids Sterols

Triglycerides

Diglycerides Phospholipids

Algal Oil Lipid Profile

Carbohydrates

Sugar analysis using HPLC is often

performed using RI detection. But RI

detection is limited by poor sensitivity

and the inability to use gradients. The

Corona ultra RS provides gradient

separations and sensitivity to low ng.

It also offers the ability to use

reversed-phase and HILIC modes of

separation, making it an ideal com-

plement to analysis with HPAE-PAD.

Lipids

HPLC is a powerful tool for lipid

analysis. With UV detection,

quantitation is made difficult by

differing relative response due to the

wide variety of structures. Other

universal detectors demonstrate a

lack of response consistency making

relative quantification difficult. With

response independent of chemical

structure, charged aerosol detection

delivers consistent, predictable

results with no optimization.

The same detector can be used to

assess purity or to perform

in-process quality control of biodiesel.

8

Application solutions

Surfactants

Minutes

Corona ultra RS (n = 5)

Other nebulizer-based detector (n = 1)

Detector overload

900

500

0

0 2 4 6 8 10 12 14 16 18 20 22 24 26

0 1 2 3 4 5 6 7 8 9 10 11 12 13

9

0

-3

10

50

019.20 20 21.20

1 6 12

2

1.1

1000

500

0

0 2 4 6 8 10 12 14 16 18 20 22 24 26

11 66 1

11 22 33 44 55 66 77 88 99 1010 1111 1212 13

Effect of Power Function

Minutes

0.70

0

-0.250.17 0.5 1 1.4

1

Prim

idon

e

Hydr

ocor

tison

e

Keto

prof

en

War

farin

Prog

ester

one

2

Prim

idon

e

Hydr

ocor

tison

e

Keto

prof

en

War

farin

Prog

ester

one

pA

pA

1.5

0

-0.5 Mass on Column (ng)

Resp

onse

(pea

k ar

ea)

Resp

onse

(pea

k ar

ea)

0 1000 1500500 25002000

1.5

0

3

Mass on Column (ng)

0 1000 1500500 25002000

1

0

2

Unique Data Algorithm

The Corona ultra RS includes

firmware to apply a power function to

the data output, often decreasing

baseline noise and linearizing the

data. With a few injections the ideal

setting can be determined.

Surfactants

Surfactants such as Triton® X-100,

which lacks a chromophore, can be

easily measured with the Corona

ultra RS detector. Unlike some other

universal detectors, the wide

dynamic range of charged aerosol

detection technology lets you assay

a full range of concentrations

without overloading the detector.

9

Pharmaceutical Analysis

Product Characterization

The Corona ultra RS detector makes it easy to

determine the concentration and purity of any

non- and many semivolatile active pharmaceutical

ingredients (APIs) and excipients. With response

independent of the chemical nature of the

analyte, almost any API or compound used

in the formulation can be measured with

predictable response.

Cleaning Validation

Cleaning validation can be both difficult and time

consuming. Using the Corona ultra RS detector, it

is possible to measure the API and cleaning agents,

either separately or together, as well as estimate

their relative amounts. A profile representing the

relative amounts of cleaning agent can be

generated even without knowing the identity

of the components.

Using the unique Thermo Scientific Acclaim™

Trinity™ P1 column and the Corona ultra RS

detector, the API, counterion, and impurity

ions can all be quantified, simultaneously. This

speeds up selection of counterions in the

development process.

10

Application solutions

0 1 2 3 4 5Minutes

10.5

-5

Sodium

Chloride

No Spike

0.1% Chloride Spike

0.15% Chloride Spike

Diclofenac

API and Counterions

–10

110

Minutes0 1.3 2.5 3.8 5.0 6.3 7.5 8.8 10.0

Typical Cleaning Agent

0.12 1 2 3 3.95Minutes

28

-2.8

DL-L

eucin

e

D-Ph

enyla

lanin

e

Aceta

min

ophe

n

Theo

phyll

ine

Eryth

rom

ycin

Napr

oxen

Na

Diclo

fenac

Na

Dode

cylsu

lfate

Na

Prog

estro

ne

Typical Pharmaceutical Agents5 overlaid concentrations from 11–170 ng

Biopharmaceutical Analysis

Analysis of biopharmaceuticals present new

challenges. Complex mixtures of large and small

molecules, many without chromophores, can be

analyzed using charged aerosol detection.

PEGylated MAb

PEGylation helps the biological stability of

therapeutic monoclonal antibodies (MAbs) but

measuring the residual PEG can be difficult. With

predictable response irrespective of the analyte,

charged aerosol detection can be used to measure

residual PEG in PEGylated proteins. With its

sensitivity and dynamic range, both low levels of

the PEG impurity and the high levels of PEGylated

protein can be measured together, without the

need to reanalyze the sample.

siRNA Delivery Vehicles

The use of siRNA as a therapeutic agent requires

optimized delivery vehicles. The detector lets you

measure the purity and stability of both lipids and

peptides used in these delivery systems.

Final Product Purity

Charged aerosol detection is ideal for peptide and

protein analysis. With no restriction on solvents, as

with UV, this detector gives you a greater range of

selectivity. And you never need worry about

acetonitrile shortages again!

From raw material qualification to final product

purity of large or small molecules, the Corona ultra

RS detector lets you see things as you have never

seen them before.

0 21 5 63 4 7 8.2Minutes

50

-50

Cationic Cell-Penetrating Peptides

MPG Transportan

Syn B1

Fast-Acting Insulin

Minutes

50

0-5

Minutes10.23 12.960.53

6.09

pA

0 2 4 8 10 12 14 16.16

InsulinUnknowns

0.1% PEG

PEG-MAb 50 µg o.c.

0.1% PEG 0.2% PEG 0.3% PEG

0 10 20

1.0

2.0

3.0

Minutes

Pegylated Protein

11

www.thermofisher.com/charged_aerosol©2016 Thermo Fisher Scientific Inc. All rights reserved. Chemstation and EZChrom are registered trademarks of Agilent Technologies. Empower is a registered trademark of Waters Corporation. Triton is a registered trademark of Dow Chemical Co. All other trademarks are the property of Thermo Fisher Scientific Inc. and its subsidiaries. Specifications, terms and pricing are subject to change. Not all products are available in all countries. Please consult your local sales representative for details.

BR70193_E 09/16S

Australia +61 3 9757 4486Austria +43 1 333 50 34 0Belgium +32 53 73 42 41Brazil +55 11 3731 5140China +852 2428 3282

Denmark +45 70 23 62 60France +33 1 60 92 48 00Germany +49 6126 991 0India +91 22 2764 2735Italy +39 02 51 62 1267

Japan +81 6 6885 1213Korea +82 2 3420 8600Netherlands +31 76 579 55 55Singapore +65 6289 1190 Sweden +46 8 473 3380

Switzerland +41 62 205 9966Taiwan +886 2 8751 6655UK/Ireland +44 1442 233555USA and Canada +847 295 7500

Discover the Corona ultra RS Detector–Giving You More for HPLC and UHPLC

In the world of HPLC/UHPLC, one detection technology stands out.

Charged aerosol detection has response independent of analyte

structure, provides consistent responses across a range of non- and

semivolatile analytes, has a wide dynamic range and broad

applicability, and is as easy to use as UV.

The Corona ultra RS detector combines the benefits of charged

aerosol detection with the speed and resolution of UHPLC for faster,

high-resolution separations while still giving superior performance

with HPLC. This detector provides the flexibility and performance for

analytical R&D, and the simplicity and reproducibility needed for

manufacturing QC/QA. It can be used for almost any analysis in

pharmaceuticals (large and small molecule), biofuels, foods and

beverages, specialty chemicals, and ions including a wide range of

applications—from basic research to quality control. This makes the

Corona ultra RS the detector of choice for your application.