Thermo Scientific Dionex Corona ultra RS Charged Aerosol Detector

Thermo Scientific Dionex Corona ultra RS
Charged Aerosol Detector
Universal detection
see what others miss
consistent • sensitive • versatile

Going beyond HPLC
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.
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.
Comparison of Charged Aerosol Detection to UV and MS
UV at 220 nm
UV at 254 nm
Corona ultra RS Detector Benefits
Void + Cl -
Propanolol
Ketoprofen
Verapamil
• Consistent response independent of
chemical structure
Charged Aerosol
Detection
• Compatibility with UHPLC
• Simple and easy to use
MS TIC
(+ ion scan 150-500AMU)
0 0.5 1 1.5 2
Minutes
2

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
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 independent
of chemical structure. With charged aerosol
detection, you can even measure many
semivolatile analytes.
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.
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.
Nebulizer and Impactor
HPLC Column Eluent
Analyte is
nebulized and
dried to produce
particles
Signal Out
Gas Inlet
Ion Trap
Collector
Analyte particles transfer
their charge to a
sensitive electrometer
Largest droplets
are eliminated
Positive charge added
to gas stream
Positive charge is transferred
to analyte particles
3

Consistent response and a
wide dynamic range
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
250,000
200,000
150,000
Detector Response for Nonvolatiles
10.7% RSD variation in CAD response
among 1.0 µg samples by flow injection
injection analysis is very similar for equivalent
100,000
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
50,000
0
Nortriptyline
Salicylic acid
Fructose
Homocysteine
Sucrose
Dextrin
Umbelliferone
Glutathione
Amitriptyline
Methionine
Lactose
Glucose
Analyte
Propranolol
Progestrone
Dibucaine
Cyclodextrin
Adrenosterone
Glucosamine
Tartaric acid
Primidone
Gentisic acid
Papaverine
4 Aminoquinaldine
Warfarin
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
140
be assessed even without knowing the
identity of the peak.
600
mV
20 minutes
heating
10 minutes
heating
Forced Degradation
Amikacin
mV
0
no
heating
0.4 0.6 0.8
Degradant
Impurities
Impurities
0
0 0.5 1 1.5 2 2.5 3 3.5 4
Minutes
4

Enhanced performance
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.
Achieving New Levels of Sensitivity
Glucose Sucrose Lactose
500 pg of each sugar
on column
˜50 ng of each sugar
on column
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.
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
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.
5

Intuitive, simple to operate, and easy
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.
400
Comparison of UHPLC to HPLC
400
200
PEG 400
Overlay of five injections
0
0 1 2
3
4 5
200
UHPLC
HPLC
0
0 2.5 5
7.5
10
Minutes
12.5 15 17.5
6

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.
4
pA
Flow Diversion
Overlay of multiple injections
3
pA
0
-.50
0.3 0.6 0.9 1.2 1.5
Minutes
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
2
1
Original chromatogram
Chromatogram with flow diversion
-0.5
0.3 0.5
1 1.5
2
Minutes
7

Application solutions
180
-5
Monoglycerides
Steroids
Fatty Acids
Fatty Alcohols
Sterols
Algal Oil Lipid Profile
Phospholipids
Diglycerides
Triglycerides
0 5 10 15 20 25 30 35 40 45 50 55 60 65 72.7
Minutes
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.
550
300
20.3
pA
Total Glycerides of Biodiesel
Triolein
1.4
5.95 7.5 8.75 9.95
Minutes
1,3-Diolein
9.75
pA
56 ng
Glycerol
6.93
28.28 29 29.33
Minutes
The same detector can be used to
assess purity or to perform
in-process quality control of biodiesel.
1-Oleylglycerol
0
-50
0 5 10 15 20 25 30 35 39.4
Minutes
300
mV
0
Carbohydrates
1
2
3
0 2 4 6 8 10
Minutes
4
5
1. Fucose
2. Fructose
3. Glucose
4. Sucrose
5. Lactose
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 complement
to analysis with HPAE-PAD.
8

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.
900
500
0
9
0
-3
0 1 2 3 4 5 6 7 8 9 10 11 12 13
Surfactants
Corona ultra RS (n = 5)
0 2 4 6 8 10 12 14 16 18 20 22 24 26
1000
10
Other nebulizer-based detector (n = 1)
50
2
500
0
19.20 20 21.20
1.1
1 6 12
Detector
overload
0
0 2 4 6 8 10 12 14 16 18 20 22 24 26
Minutes
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.
1.5
pA
0
-0.5
0.70
pA
0
1
2
Primidone
Primidone
Hydrocortisone
Hydrocortisone
Effect of Power Function
-0.25
0.17 0.5 1 1.4
Ketoprofen
Ketoprofen
Warfarin
Warfarin
Progesterone
Progesterone
Response (peak area) Response (peak area)
3
1.5
0
2
1
0
0 500 1000 1500 2000 2500
Mass on Column (ng)
0 500 1000 1500 2000 2500
Mass on Column (ng)
Minutes
9

Application solutions
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.
28
DL-Leucine
D-Phenylalanine
Typical Pharmaceutical Agents
5 overlaid concentrations from 11–170 ng
Acetaminophen
Theophylline
-2.8
0.12 1 2 3 3.95
Minutes
Erythromycin
Naproxen Na
Diclofenac Na
Dodecylsulfate Na
Progestrone
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.
10.5
Sodium
API and Counterions
Chloride
Diclofenac
0.15% Chloride Spike
0.1% Chloride Spike
No Spike
-5
0 1 2 3 4 5
Minutes
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.
110
–10
Typical Cleaning Agent
0 1.3 2.5 3.8 5.0 6.3 7.5 8.8 10.0
Minutes
10

3.0
0.1% PEG
Pegylated Protein
PEG-MAb 50 µg o.c.
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.
50
Cationic Cell-Penetrating Peptides
MPG
Transportan
Syn B1
0 1 2
3 4 5 6
7 8.2
Minutes
50
2.0
1.0
6.09
pA
0.3% PEG
0.2% PEG
0.1% PEG
0 10 20
Minutes
Fast-Acting Insulin
Unknowns
0.53
10.23 Minutes 12.96
Insulin
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
-5
0 2 4 6
8 10 12 14 16.1
Minutes
11

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.
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