title: Separation, characterization, and quantitation of process-related substances of the anti-hypertensive drug doxazosin mesylate by reversed-phase LC with PDA and ESI-MS as detectors.
abstract: A simple and rapid reversed-phase liquid chromatography (LC) method with photodiode array (PDA) and electrospray ionization (ESI)-mass spectrometry (MS) as detectors was developed and validated to separate, identify, and quantitate the related substances of Doxazosin mesylate (DXZN) for monitoring the reactions involved during process development. The high-performance liquid chromatography profiles of related-substances of DXZN are used as fingerprints to follow the procedures used in the manufacturing units. The separation is accomplished on an Inertsil ODS-3 column with acetonitrile-ammonium acetate (10 mM, pH 4.0) as the mobile phase, using a gradient elution mode and monitoring the eluents by a photodiode array detector at 265 nm at ambient temperature. LC-ESI-MS-MS is used to identify the additional impurities formed during the synthesis. The identified impurities were synthesized and characterized by UV, Fourier transform-IR, 1H NMR, and MS data. The detection limits for the impurities are 0.74 - 4.14 x 10(-9) g, and the method is found to be suitable not only for the monitoring of synthetic reactions, but also for quality assurance of DXZN in bulk drugs and formulations.
authors.affiliation: HPLC/UV Group, Division of Analytical Chemistry, Discovery Laboratory, Indian Institute of Chemical Technology, Hyderabad-50 0007, India. rnrao55@yahoo.com
authors.forename: R
authors.initials: R
authors.lastname: Nageswara Rao
authors.forename: D
authors.initials: D
authors.lastname: Nagaraju
authors.forename: A K
authors.initials: AK
authors.lastname: Das
authors.forename: Nivedita
authors.initials: N
authors.lastname: Jena
mesh_terms: D000959:Antihypertensive Agents / Q000032:analysis / Q000737:chemistry / Q000302:isolation & purification*; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D017292:Doxazosin / Q000032:analysis / Q000737:chemistry / Q000302:isolation & purification*; D012015:Reference Standards; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D013057:Spectrum Analysis / Q000379:methods*; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D000959:Antihypertensive Agents; D017292:Doxazosin