Development and Validation of Rapid Stability-Indicating RP-HPLC Method for Assay and Related Substances of Solifenacin
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ORIGINAL
Development and Validation of Rapid Stability‑Indicating RP‑HPLC Method for Assay and Related Substances of Solifenacin Succinate Rajiv A. Jadhav1,2 · Yogeesha M. Sanil2 · Sunil G. Shankarwar2 · Anil G. Shankarwar2 · Rajendra P. Pawar2 · Saroj R. Bembalkar2 Received: 21 February 2020 / Revised: 21 June 2020 / Accepted: 24 June 2020 © Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract A simple, inexpensive, rapid and novel stability-indicating reversed-phase high-performance liquid chromatographic method employing Zorbax-CN column has been developed and validated for the determination of both, assay and related substances of Solifenacin Succinate (SOL) drug substance and in its drug product. Forced degradation study of SOL was performed at acid, base, oxidative, photolytic and thermal stress conditions. Significant degradation was observed only in acidic and basic conditions. Four process and degradation impurities and have been identified by LC–MS and characterized by 1H NMR and FT-IR spectroscopy. The baseline separation of the impurities was achieved by gradient elution using phosphate buffer (pH 3.5) and a mixture of solvents (acetonitrile, methanol, and water), as mobile phase at a flow rate of 1.0 mL min−1. All impurities were quantified using a photodiode array detector (PDA) at 220 nm. The developed RP-HPLC method was validated in agreement with ICH requirements. The forced degradation studies proved the stability-indicating power of the method and hence, the validated method is useful for the intended use in routine analysis of SOL as bulk drug and in respective dosage forms. The salient feature of the presented method could be applied for assay and related substances determination of SOL in pharmaceutical laboratories and industries. Keywords Degradation impurities · Forced degradation · Method validation · Solifenacin succinate · Stability-indicating · RP-HPLC
Introduction Solifenacin succinate (SOL), a butanedioic acid is described chemically as (1S)-(3R)-1-azabicyclo [2.2.2] oct-3-yl3,4-dihydro-1-phenyl-2(1H)-iso-quinolinecarboxylate(1:1) succinate. The empirical formula of SOL is C23H26N2O2. C4H6O4 and molecular weight is 480.55. The chemical structure of SOL is shown in Fig. 1. The SOL salt is a tertiary amine and belongs to antichlolinergic property, which is used for symptomatic treatment of overactive bladder (OAB) [1]. The acetylcholine and muscarinic receptors perform distinct actions in various organs in a body, such as contraction of smooth muscles, saliva production, and iris * Saroj R. Bembalkar [email protected] 1
Wockhardt Research Centre, D-4, MIDC, Chikalthana, Aurangabad 431006, India
Department of Chemistry, Deogiri College, Aurangabad 431005, India
2
sphincter function, etc. The major therapeutic target organ is the urological tract of anticholinergics such as SOL. Moreover, SOL is a competitive M3 receptor antagonist and its peak plasma concentration of 40.6 ng/mL was reached 3–8 h after long-term oral administration. SOL has 98% of plasma
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