Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2014 Sep 8;83(1):65-83.
doi: 10.3797/scipharm.1407-18. Print 2015 Jan-Mar.

Isolation, Identification, and Characterisation of Degradation Products and the Development and Validation of a Stability-Indicating Method for the Estimation of Impurities in the Tolterodine Tartrate Formulation

Lakkireddy Prakash  1 , Malipeddi Himaja  2 , Rudraraju Vasudev  3
Affiliations

Isolation, Identification, and Characterisation of Degradation Products and the Development and Validation of a Stability-Indicating Method for the Estimation of Impurities in the Tolterodine Tartrate Formulation

Lakkireddy Prakash et al. Sci Pharm. .

Abstract

A short and sensitive stability-indicating gradient RP-UPLC method was developed for the quantitative determination of process-related impurities and degradation products of tolterodine tartrate in pharmaceutical formulations. The method was developed by using the Waters ACQUITY UPLC™ BEH shield RP18 (2.1 × 100 mm, 1.7 μm) column with a mobile phase containing a gradient mixture of solvent A and B at a detection wavelength of 210 nm. During the stress study, the degradation products of tolterodine tartrate were well-resolved from tolterodine and its impurities and the mass balances were found to be satisfactory in all the stress conditions, thus proving the stability-indicating capability of the method. The developed method was validated as per ICH guidelines with respect to specificity, linearity, limit of detection and quantification, accuracy, precision, ruggedness, and robustness. During the stability (40°C/75% RH, 3 months) analysis of the drug product, one unknown impurity was detected by the above stability-indicating method. The unknown impurity was isolated by preparative HPLC and subjected to mass and NMR studies. Based on the spectral data, the unknown impurity was characterised as 2-(3-amino-1-phenylpropyl)-4-methylphenol (des-N,N-diisopropyl tolterodine). Structural elucidation of the impurity by spectral data is discussed in detail.

Keywords: Characterisation; Development; Stability-indicating; Tolterodine tartrate; UPLC.

PubMed Disclaimer

Figures

Fig. 1
Fig. 1
HR-MS and MS–MS data of tolterodine and the unknown impurity (a) HR-MS spectra of tolterodine, (b) MS–MS spectra of tolterodine, (c) HR-MS spectra of the impurity, (d) MS–MS spectra of the impurity
Fig. 2
Fig. 2
Chemical structures of tolterodine and the unknown impurity with numbering
Fig. 3
Fig. 3
Overlay of the NMR spectra of the unknown impurity and tolterodine
Fig. 4
Fig. 4
Typical overlay chromatogram of the blank, placebo, and impurity mixture
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Drugs.com, Tolterodine tartrate. [(accessed17 July 2013)]. http://www.drugs.com/monograph/tolterodine-tartrate.html .
    1. Rxlist, Tolterodine tartrate. [(accessed17 July 2013)]. http://www.rxlist.com/detrol-la-drug.html .
    1. Drug Bank, Tolterodine tartrate. [(accessed17 July 2013)]. http://www.drugbank.ca/drugs/DB01036 .
    1. Nanda RK, Gaikwad J, Prakash A. Simultaneous spectrophotometric Estimation of Tolterodine on Pharmaceutical Dosage form. Int J PharmTechRes. 2009;2:312–314.
    1. Nanda RK, Gaikwad J, Prakash A. Estimation of Tamsulosin and Tolterodine in its pharmaceutical dosage form by Spectrophotometric method. Int J PharmTechRes. 2009;1:420–423.

LinkOut - more resources