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
Open Access
- 1 January 2015
- journal article
- Published by MDPI AG in Scientia Pharmaceutica
- Vol. 83 (1), 65-83
- https://doi.org/10.3797/scipharm.1407-18
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 x 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 quantifica-tion, 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
This publication has 14 references indexed in Scilit:
- Structure elucidation of a process-related impurity of dapoxetineJournal of Pharmaceutical and Biomedical Analysis, 2014
- Impurity Profiling and a Stability-Indicating UPLC Method Development and Validation for the Estimation of Related Impurities of Halobetasol Propionate in Halobetasol Propionate 0.05% (w/w) CreamJournal of Chromatographic Science, 2014
- Isolation, identification and characterization of degradant impurities in Tolterodine tartrate formulationJournal of Pharmaceutical and Biomedical Analysis, 2014
- Reverse-phase, high performance liquid chromatographic method for the determination of tolterodine tartrate in routine quality control samples.2010
- An enantiospecific HPLC method for the determination of (S)-enantiomer impurities in (R)-tolterodine tartarate.2007
- High performance liquid chromatography-electrospray ionization mass spectrometric determination of tolterodine tartrate in human plasmaJournal of Chromatography B, 2005
- A validated chiral HPLC method for the enantiomeric separation of tolterodine tartarateJournal of Pharmaceutical and Biomedical Analysis, 2004
- Column switching in capillary liquid chromatography–tandem mass spectrometry for the quantitation of pg/ml concentrations of the free basic drug tolterodine and its active 5-hydroxymethyl metabolite in microliter volumes of plasmaJournal of Chromatography A, 1998
- The use of hyphenated LC–MS technique for characterisation of impurity profiles during drug developmentJournal of Pharmaceutical and Biomedical Analysis, 1998
- Determination of tolterodine and the 5-hydroxymethyl metabolite in plasma, serum and urine using gas chromatography-mass spectrometryJournal of Pharmaceutical and Biomedical Analysis, 1997