Tolterodine, a quaternary ammonium compound, is used to treat urinary incontinence. To create the drug substance, tolterodine
is paired with tartrate to form tolterodine tartrate. This drug substance can then be used to create drug products. One way
to confirm the amount of a drug substance in a drug product is to assay for its counterion. This is especially true for counterions
such as tartrate that are unlikely to originate from any other sample components. Ion chromatography (IC) with suppressed
conductivity detection is a common technique for counterion determinations. Here we report an IC method to determine tartrate
in a tolterodine tartrate drug product that is faster, requires less labour and eliminates analyst exposure to strong acid
relative to a recently published IC method (1).
A Thermo Scientific Dionex ICS-5000 IC System configured with an EG Eluent Generator module, DC Detector/Chromatography Compartment
and CD Conductivity Detector was used. Samples were introduced by an AS-AP Autosampler. All data collection and processing
was controlled by Thermo Scientific Dionex Chromeleon Chromatography Data System software. Complete experimental details are
found in reference 2.
Figure 1 Trace A shows the determination of tartrate in a capsule drug product containing tolterodine tartrate. Tartrate is
resolved from other anions in the sample using a Thermo Scientific Dionex IonPac AS20 Hydroxide-Selective Anion-Exchange Column
set with 20 mM potassium hydroxide. The eluent is produced by the eluent generator, and therefore the labor and possible error
associated with eluent preparation are eliminated. Tartrate is detected by suppressed conductivity in the recycle mode, indicating
that the analyst does not have to prepare a strong acid solution for suppressed conductivity detection. Figure 1 Trace B shows
the same sample to which an additional 4 mg/L tartrate was added. For a set of five samples there was 100% recovery of the
added tartrate. The same unfortified five samples had 98.4% of the labeled amount of drug substance as measured by tartrate
concentration. Both results indicate good method accuracy. Overall this is an accurate IC method for determining tartrate
that does not require the analyst to prepare eluent or strong acid regenerant.
Figure 1: Determination of tartrate in a drug capsule: Trace A shows the sample and Trace B is the sample to which 4 mg/L
tartrate was added before sample preparation.
(1) G.R. Deshpande, B.M. Rao, and N. Someswararao, "Quantitative Determination of Tartaric Acid in Tolterodine Tartrate by
Ion Chromatography Using Conductivity Detection," RASAYAN J. Chem., 2101–2107 (2009).
(2) Thermo Scientific Application Note 1002: Determination of Tartaric Acid in Tolterodine Tartrate Drug Products by IC with
Suppressed Conductivity Detection, Sunnyvale, California, USA, 2012. [Online] http://www.dionex.com/en-us/webdocs/113488-AN1002-IC-TartaricAcid-TolterodineTartrate-02May2012-LPN3065.pdf (accessed May 31, 2012).
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