title: 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.
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.
authors.affiliation: Department of Analytical Research and development, Dr. Reddy's, Laboratories Ltd, IPDO, Hyderabad, 500072, Telangana, India; Pharmaceutical Chemistry Division, School of Advanced Sciences, VIT University Vellore-632014, TN, India.
authors.forename: Lakkireddy
authors.initials: L
authors.lastname: Prakash
authors.affiliation: Pharmaceutical Chemistry Division, School of Advanced Sciences, VIT University Vellore-632014, TN, India.
authors.forename: Malipeddi
authors.initials: M
authors.lastname: Himaja
authors.affiliation: Department of Analytical Research and development, Dr. Reddy's, Laboratories Ltd, IPDO, Hyderabad, 500072, Telangana, India.
authors.forename: Rudraraju
authors.initials: R
authors.lastname: Vasudev
keywords: Characterisation; Development; Stability-indicating; Tolterodine tartrate; UPLC
references.citation: J Chromatogr A. 1998 Dec 18;828(1-2):209-18
references.pmid: 9916307
references.citation: J Pharm Biomed Anal. 2014 Mar;90:215-21
references.pmid: 24384498
references.citation: Pharmazie. 2007 Mar;62(3):170-3
references.pmid: 17416191
references.citation: J Pharm Biomed Anal. 1997 Sep;16(1):155-65
references.pmid: 9447563
references.citation: J Pharm Biomed Anal. 1998 Dec;18(4-5):707-14
references.pmid: 9919972
references.citation: J Pharm Biomed Anal. 2004 Sep 3;35(5):1279-85
references.pmid: 15336373
references.citation: J Chromatogr B Analyt Technol Biomed Life Sci. 2005 Sep 25;824(1-2):92-8
references.pmid: 16043426
references.citation: J Pharm Biomed Anal. 2014 Aug 5;96:272-7
references.pmid: 24793500
references.citation: J Chromatogr Sci. 2015 Jan;53(1):112-21
references.pmid: 24795078
references.citation: PDA J Pharm Sci Technol. 2009 May-Jun;63(3):234-9
references.pmid: 20069796
references.citation: J Pharm Biomed Anal. 2013 Dec;86:11-35
references.pmid: 23969330
references.citation: J Chromatogr Sci. 2015 Jan;53(1):122-6
references.pmid: 24837014
references.citation: J Chromatogr B Biomed Sci Appl. 1999 Dec 24;736(1-2):247-53
references.pmid: 10677005
references.citation: J Pharm Biomed Anal. 2014 Dec;101:102-22
references.pmid: 24853620