Characterization of Forced Degradation Products of Netarsudil: Optimization and Validation of a Stability-Indicating RP-HPLC Method for Simultaneous Quantification of Process-Related Impurities.
| Autor: | Anna VR; Koneru Lakshmaiah Education Foundation, Department of Engineering, Chemistry College of Engineering, Andhra Pradesh, India., Kumar BS; Koneru Lakshmaiah Education Foundation, Department of Engineering, Chemistry College of Engineering, Andhra Pradesh, India., Harish J; Koneru Lakshmaiah Education Foundation, Department of Engineering, Chemistry College of Engineering, Andhra Pradesh, India., Tatavarti BK; Kakaraparti Bhavanarayana College (Autonomous), Department of Chemistry, Andhra Pradesh, India., Eswarlal T; Koneru Lakshmaiah Education Foundation, Department of Engineering Mathematics, College of Engineering, Andhra Pradesh, India. |
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| Jazyk: | angličtina |
| Zdroj: | Turkish journal of pharmaceutical sciences [Turk J Pharm Sci] 2024 Jul 12; Vol. 21 (3), pp. 224-233. |
| DOI: | 10.4274/tjps.galenos.2023.99148 |
| Abstrakt: | Objectives: The aim of this study is to examine resolution, identification, and characterization of forced degradation products of netarsudil by liquid chromatography-tandem mass spectrometry by validating a simple and sensitive high-performance liquid chromatography method for the resolution, identification, and quantification of two process-related impurities in netarsudil. Materials and Methods: Chromatographic separation was accomplished on a ZORBAX Eclipse XDB C18 (250 x 4.6 mm; 5 µ id) column at room temperature as the stationary phase and 257 nm as the detector wavelength with the mobile phase consisting of acetonitrile, methanol, and pH 4.6 phosphate buffer in 45:35:20 ( v/v ) at 1.0 mL/min flow rate in isocratic elution. Results: The method reported very sensitive detection limits of 0.008 µg/mL for impurity 1 and 0.003 µg/mL for impurity 1. The method produces a calibration curve linear in the concentration level of 25-200 for netarsudil and 0.025-0.2 µg/mL for impurities. The proposed method gives acceptable results for other validation parameters such as accuracy, precision, ruggedness, and robustness. The drug was subjected to various stress conditions such as acid, base, peroxide, and thermal and ultraviolet light to investigate the stability-indicating ability of the method. Considerable degradation was observed in stress studies, and the degradation products were well resolved from process-related impurities. The characterization of degradation products was performed on the basis of collision-induced dissociation mass spectral data, and the possible structures of the six degradation compounds of netarsudil were proposed. Conclusion: The outcomes of other validation studies were likewise satisfactory and proven adequate for the regular analysis of netarsudil and its process-related impurities in bulk drug and pharmaceutical dosage forms and can also be applied for the evaluation of the stress degradation mechanism of netarsudil. Competing Interests: Conflict of Interest: No conflict of interest was declared by the authors. (Copyright© 2024 The Author. Published by Galenos Publishing House on behalf of Turkish Pharmacists’ Association.) |
| Databáze: | MEDLINE |
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