Page 8 - Shimadzu’s Solutions for Impurities Analysis

Analysis of Ultra-Trace Impurities Structural Analysis of Ultra-trace
Co-Sense for LC/MS System
Impurities
2D-LC/LCMS-IT-TOF ®

˙ Structural Analysis of Ultra-trace Impurities Using the
Co-Sense for LC/MS System
Non-volatile mobile phase conditions using phosphate buffer are to capture a variation in an elution sequence or impurities eluted in
commonly applied in HPLC methods in QA divisions; however; the proximity to the main components. Therefore, it requires extreme
conditions (volatile mobile phase) need to be changed for caution, as well as valuable time and resources, to covert established
atmospheric ionization methods when performing LC/MS analysis. HPLC method conditions, causing delays when responding to requests
Changing the conditions is risky, as the change can result in a failure for identification of impurities from production departments.

®
˙ The Co-Sense for 2D-LC/LCMS-IT-TOF Before elution of impurity’s peak
FDA Regulations on
Genotoxic Impurities
Nonvolatile mobile phase goes to drain
System Features via the designated loop
ɾ On-line desalting and separation from ion-pair reagent permit the
structural analysis of unidentified impurity peaks by mass
1st-D column
[Option Box vp] Valve A
spectrometry without relying on the LC separation conditions. 2nd-D column To MS
®
ɾ LCMS-IT-TOF , a mass spectrometer combining QIT (ion trap) and
Flow line passes
n
TOF (time-of-flight) technologies, provides MS capability by the QIT through loop
and precise, high-resolution mass measurement capabilities by TOF.
n
Precise mass measurement in MS , which is not possible using a CTO.RVL CTO.RVR [column oven]
[column oven]
Loop to be taken is selected
typical LC/MS/MS, is now a reality. 10 μL loop, SUS x 6 [Option Box vp] Valve D
[Option Box vp] Valve C
ɾ Shimadzu offers a versatile software solution to support workflows
covering detection of ultra-trace impurities, composition prediction
and structural prediction. MetID Solution Metabolite Structural When the peak top moves to
the center of the loop
Analysis Software is capable of automated extraction of a Impurity is fractionated and remains
Residual Solvents
n
structurally-relevant peak using MS spectral similarity. Composition in the designated loop
FDA Regulations on
Prediction Software (Formula Predictor) is capable of formula
prediction using mass accuracy as well as by combining isotopic
1st-D column [Option Box vp] Valve A
n
pattern scoring, chemical rule and MS filtering. 2nd-D column To MS
ɾ When analyzing an ultra-trace impurity and it cannot be determined
Reverts to
whether the samples will be detected as positive or negative ions, initial state
the high-speed, stable ion polarity switching mode ensures mass
spectral information will be obtained. CTO.RVL CTO.RVR [column oven]
[column oven]
Loop goes offline
10 μL loop, SUS x 6
[Option Box vp] Valve D
[Option Box vp] Valve C
˙ Operating Principle of System
The Co-Sense for LC/MS system consists of three parts; 1 dimensional Initial status
st
separation for impurities, trap concentration/desalting of target Nonvolatile mobile phase goes to MS
(or drain) without passing through the loop
nd
impurities and a 2 dimension analyzer (LC/MS). Phosphate and other
st
solutions contained in the mobile phase in the 1 dimensional
separation are removed at the trap concentration/desalting part and
FDA Regulations on
Inorganic Impurities
1st-D column
[Option Box vp] Valve A
nd
the target impurity is introduced to the 2 dimension. In case an ion 2nd-D column To MS
st
pair solution is used for separation in the 1 dimension, the target
impurity and the ion pair solution are separated in the 2 dimension.
nd
This enables mass analysis of the target impurity without selecting
st
analytical conditions at the 1 dimension. CTO.RVL CTO.RVR [column oven]
[column oven]
Impurities in loop
10 μL loop, SUS x 6 [Option Box vp] Valve D
[Option Box vp]
˙ Valve Sequence Valve C
Initial status In analysis
Nonvolatile mobile phase goes to drain Nonvolatile mobile phase goes to MS while
after passing through the detector pushing out the impurity in the loop
1st-D column
1st-D column [Option Box vp] Valve A
[Option Box vp] Valve A 2nd-D column
2nd-D column To MS To MS
Support from Shimadzu
Flow path includes loop
CTO.RVL CTO.RVR [column oven]
CTO.RVL CTO.RVR [column oven] [column oven]
[column oven]
Loop to be analyzed is selected
10 μL loop, SUS x 6
10 μL loop, SUS x 6 [Option Box vp] Valve D [Option Box vp] Valve D
[Option Box vp] Valve C [Option Box vp] Valve C
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