title: Development and validation of a reversed-phase HPLC method for monitoring of synthetic reactions during the manufacture of a key intermediate of an anti-hypertensive drug.
abstract: A reversed-phase high-performance liquid-chromatographic method for monitoring of reactions involved in process development of a key intermediate of antihypertensive drugs, e.g, doxazosin mesylate, prazosin, alfuzosin, terazosin, etc., has been developed and validated. The HPLC profiles of impurities of 4-amino-2-chloro-6,7-dimethoxyquinazoline were used as fingerprints to follow the synthetic procedures in the manufacturing unit. The separation was accomplished on an Inertsil ODS-3 column with isocratic elution using acetonitrile-ammonium acetate (10 mM; pH 4.0; 50:50 v/v) as mobile phase and a photodiode array detector set at 240 nm at ambient temperature. The method was validated with respect to accuracy, precision, linearity, and limits of detection and quantification. The method could detect the impurities at a level of 0.01 to 0.20 microg/mL and it was found to be suitable not only for monitoring of reactions but also for quality assurance of 4-amino-2-chloro-6,7-dimethoxyquinazoline.
authors.affiliation: Analytical Chemistry Division, Discovery Laboratory, Indian Institute of Chemical Technology, Hyderabad, India. rnrao55@yahoo.com
authors.forename: Ramisetti Nageswara
authors.initials: RN
authors.lastname: Rao
authors.forename: Dongari
authors.initials: D
authors.lastname: Nagaraju
authors.forename: Nivedita
authors.initials: N
authors.lastname: Jena
authors.forename: Gullapalli
authors.initials: G
authors.lastname: Kumaraswamy
mesh_terms: D000959:Antihypertensive Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000592:standards; D002851:Chromatography, High Pressure Liquid / Q000379:methods* / Q000592:standards / Q000706:statistics & numerical data; D004340:Drug Contamination; D011786:Quality Control; D011799:Quinazolines / Q000138:chemical synthesis / Q000737:chemistry / Q000592:standards; D013056:Spectrophotometry, Ultraviolet
chemical_list: D000959:Antihypertensive Agents; D011799:Quinazolines