Sangoi, Maximiliano da Silva

Steppe, Martin

English

Lume 5.8

caderno d•farmácla ISSN 0102-6593 Órgão Oficial da Faculdade de Farmácia da Universidade Federal do Rio Grande do Sul volume 26, Suplemento, 201 O CONTROLE DE QUALIDADE DE INSUMOS FARMACÊUTICOS E MEDICAMENTOS Quality control of pharmaceutical raw materiais and medicines lJ-roz..9 ~----- -----------~~ ~~~----153 LIQUID CHROMATOGRAPHIC METHOD FOR THE DETERMINATION OF FESOTERODINE IN TABLET DOSAGE FORMS USING EXPERIMENTAL DESIGNS Sangoi M.S.; Steppe M. Laboratório de Ensino e Pesquisa em Controle de Qualidade, Faculdade de Farmácia, UFRGS. *Doutorando- Início: 2009/1 lntroduction: Overactive bladder (OAB) syndrome is defined as urinary urgency, with or without urgency urinary incontinence, usually accompanied by increased micturition frequency and nocturia. lhe condition is chronic with an overall prevalence of approximately 12% in the general population. Fesoterodine fumarate (FESO) is a urinary antispasmodic, in a modified release preparation, licensed for the treatment of symptoms that may occur in patients with OAB syndrome. FESO is a novel nonselective oral antimuscarinic agent that acts functionally as a prodrug. lt is rapidly and extensively hydrolyzed by nonspecific esterases to the active metabolite 5-hydroxymethyltolterodine (5-HMT), which is responsible for ali antimuscarinic activity of FESO. FESO is commercially available, but at the moment is not included in any pharmacopoeia, and no analytical method is reported for the quantitativa analysis of the drug in presence of its degradation products. Objective: The aim of the present study was to develop and validate a high-throughput stability-indicating reversed-phase liquid chromatography (RP-LC) method for the determination of FESO in tablet dosage forms using experimental designs. Method: Tablets were accurately weighed and crushed to a fine powder, appropriated amounts were transferred into volumetric flasks and diluted with methanol at final concentration of 200 j.Jg/ml. lhe experiments were performed using a C18 column (100 x 4.6 mm i.d.). The Shimadzu LC system was operated isocratically at controlled temperatura (45 'C) using a mobile phase of acetonitrile-methanol-ammonium acetate (20 mM, pH 3.8) (30: 15:55, v/v/v), run at a flow rate of 2.4 mllmin. The injection volume was 10 J..ll and PDA detection was set up at 208 nm. The peak areas were integrated automatically by computar using a Shimadzu Class VP software program. The mass spectrometry (MS) detection (Model Quattro LC, Micromass) was used do identify the degradation products produced during the forced degradation studies, determined by subjecting a tablet solution (200 j.Jg/ml) to accelerated degradation by acidic, basic, thermal, oxidative, and photolytic conditions. Method validation investigated parameters such as the specificity, linearity, range, recovery, accuracy, precision, and limit of quantitation (LoQ) and limit of detection (LoD), according to the lnternational Conference on Harmonization (ICH) guideline. Results and discussion: Short column was incorporated for obtain high-throughput assays requested in industrial pharmaceutical analysis. Thus, the chromatographic separation was obtained within 2.5 min and it was linear in the concentration range of 5-150 j.Jg/ml (f= 0.9995). lhe specificity and stability-indicating capability of the method are proven through degradation studies, which also showed that there is no interference of the formulation excipients, showing that peak is free from any coeluting peak. The combination of LC with MS has become a powerful qualitativa and quantitativa analytical technique essential in various research fields, as quality control analysis. The six major degradation products were identified and namely as DP-1 to DP-6 and the degradation pathway of FESO has been proposed. Plackett-Burman experimental design and a 23 full factorial design were employed to estimate the robustness and intermediate precision, respectively. Moreover, method validation demonstrated acceptable results for accuracy, with a mean value of 99.46% (RSD=1.84%). The proposed method was successfully applied for the quantitativa analysis of FESO in pharmaceutical dosage forms. Conclusion: The results of the validation studies show that the stability-indicating RP-LC method is specific, accurate and has significant linearity, precision and robustness, without any interference from the excipients and degradation products. The major degradation products were analysed and identified by MS. lherefore, the proposed method was applied for the fast analysis of FESO in the tablet dosage forms, contributing to improve the quality control of pharmaceutical preparations containing this drug. Acknow/edgements: Financiai support from CAPES/Brazil. 

Liquid chromatographic method for the determination of fesoterodine in tablet dosage forms using experimental designs

https://lume.ufrgs.br/bitstream/10183/267801/1/000770028.pdf

Liquid chromatographic method for the determination of fesoterodine in tablet dosage forms using experimental designs

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