analysis of loratadine and related substances using the … · 2015-07-23 · goal successfully...
TRANSCRIPT
GOALSuccessfully transfer the compendial HPLC
method for the analysis of Loratadine, as written,
to the ACQUITY UPLC® H-Class System and sub-
sequently migrate to a UPLC®-optimized method.
BAckGrOundDrug substances and drug products are routinely
analyzed for impurities and related substances and
for assay of active pharmaceutical ingredient (API)
content to ensure efficacy and safety of the phar-
maceutical product. The U.S. Pharmacopeia (USP)
compendial methods used for these analyses typi-
cally employ HPLC utilizing long columns resulting
in excessive run times. In the case of Loratadine
and Loratadine Tablets, an antihistamine drug
used to treat allergies, the USP method for Related
Substances (RS) and Assay uses a 4.6 mm x 15
cm L7 column at 1.0 mL/min with an isocratic run
time of approximately 20 minutes. A second RS
method (designated Test 2) for Loratadine prepared
by a different synthetic route calls for a 4.6 mm x
25 cm L1 column at 1.2 mL/min with a gradient
run time of 50 minutes in order to separate an
additional impurity. Any reduction in analysis time
can correspond to significant cost savings for an
analytical lab.
Analysis of Loratadine and Related Substances using the ACQUITY UPLC H-Class System
develop a method that is approximately five times faster and produces data of equal or better quality than current HPLc methods by using the AcQuITY uPLc H-class System. This system provides an ideal solution for laboratories running uSP compendial HPLc methods or that are looking to migrate current methods to the efficiency and cost-effectiveness of uPLc.
[ technology brief ]
THe SOLuTIOnThe method provided from the USP was run on a traditional HPLC system (Alliance®
HPLC with a 2998 Photodiode Array Detector) exactly as written in the monograph.
The entire analysis was then run, exactly as written, on the ACQUITY UPLC H-Class
System. Results from these two assays (retention time reproducibility, relative
retention time, and impurity levels) were compared to show the ACQUITY UPLC
H-Class System has the ability to perform compendial methods of this type equally
or better than traditional HPLC technology.
The compendial HPLC method was transferred to a UPLC method using the instru-
ment’s built-in ACQUITY UPLC Columns Calculator. Using this newly calculated
method, the entire sample set was analyzed, and the results compared (retention
time reproducibility, relative retention times, and impurity levels) to the HPLC
results. Using this significantly shorter run time method with a reduction from 20
minutes for the isocratic run to 4 minutes, the results compared favorably to those
obtained both from the ACQUITY H-Class System running the HPLC method and the
traditional HPLC system (Figure 1).
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Waters, ACQUITY UPLC, and UPLC are registered trademarks of Waters Corporation. MassPREP, Auto•Blend, and The Science of What’s Possible are trademarks of Waters Corporation. All other trademarks are the property of their respective owners.
©2010 Waters Corporation. Produced in the U.S.A.January 2010 720003325EN LB-PDF
[ technology brief ]
A compendial HPLC method for the assay of Loratadine and
Related Substances was successfully run as written on the
Waters ACQUITY UPLC H-Class System. Results obtained on the
system were equivalent to those obtained on the Alliance HPLC
System, meeting the requirements of the USP method.
With the help of the ACQUITY UPLC Columns Calculator, the
method was transferred to UPLC on the ACQUITY UPLC H-Class
System. This new UPLC method was approximately five times
Imp
1 -
6.01
3
Imp
2 -
6.52
3 Lora
tadi
ne -
8.3
62
-0.002
0.000
0.002
0.004
0.006
0.008
0.010
0.012
0.014
0.016
Minutes
Minutes
4.50 5.00 5.50 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 14.50 15.00
HPLC separationAlliance 2695
Imp
1 -
6.77
8
Imp
2 -
7.43
7
Lora
tadi
ne -
9.7
07
-0.0005
0.0000
0.0005
0.0010
0.0015
0.0020
0.0025
0.0030
0.0035
4.50 5.00 5.50 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 14.50 15.00 15.50 16.00 16.50 17.00 17.50 18.00 18.50 19.00
HPLC separationACQUITY UPLC H-Class
Imp
1 -
1.44
0
Imp
2 -
1.57
5
Lora
tadi
ne -
2.0
33
AU
0.000
0.001
0.002
0.003
0.004
0.005
0.006
0.007
0.008
0.009
0.010
Minutes1.00 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 3.40 3.50 3.60 3.70 3.80 3.90 4.00
UPLC separationACQUITY UPLC H-Class
Peak RT %RSD Rel. RT % Impurity
Impurity 1 6.024 min 0.319% 0.718 0.0185%
Impurity 2 6.536 min 0.345% 0.779 0.0443%
Loratadine 8.387 min 0.373% 1.000 n/a
Peak RT %RSD Rel. RT % Impurity
Impurity 1 6.762 min 0.269% 0.697 0.0188%
Impurity 2 7.430 min 0.297% 0.766 0.0419%
Loratadine 9.698 min 0.256% 1.000 n/a
Peak RT %RSD Rel. RT % Impurity
Impurity 1 1.446 min 0.257% 0.708 0.0188%
Impurity 2 1.581 min 0.256% 0.774 0.0425%
Loratadine 2.042 min 0.335% 1.000 n/a
AU
AU
Figure 1. Comparison of Loratadine and Related Substances run by HPLC
on Alliance HPLC System vs. HPLC run on ACQUITY
UPLC H-Class and UPLC run on the same.
faster and produced data of equal or better quality than the current HPLC
method. When high quality results are produced more quickly, laboratory
productivity increases and cost-per-sample decreases.
The Waters ACQUITY UPLC H-Class System is an ideal solution for
laboratories running USP compendium HPLC methods or that are seeking
to migrate their current HPLC methods to the more efficient and cost
effective UPLC technology platform.
SummArY