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).

Waters Corporation 34 Maple Street, Milford, MA 01757 U.S.A. T: 1 508 478 2000 F: 1 508 872 1990 www.waters.com

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