title: Isolation and characterization of a novel acid degradation impurity of Amlodipine Besylate using Q-TOF, NMR, IR and single crystal X-ray.
abstract: Forced degradation of Amlodipine Besylate (AMD) in acidic condition gave rise to a potential unknown impurity. This unknown acid degradation product (ADP) was evaluated using a new-reverse-phase high performance liquid chromatography (HPLC), where it was eluted at 1.24 relative retention time to AMD peak. ADP was isolated using preparative HPLC from degradation mixture. Later, structure of ADP was elucidated using high resolution MS, multidimensional NMR and FTIR spectroscopic techniques, and characterized as ethyl-6-(2-chlorophenyl)-8-methyl-3,4,6,7-tetrahydro-2H-benzo[b][1,4]oxazine-5-carboxylate. The presence of ADP recemic mixture was confirmed by polarimeter and chiral HPLC. Given the complexity associated with ADP generation, single crystal X-ray crystallography technique was used to confirm proposed structure. In addition, reaction mechanism was postulated and confirmed using computational chemistry. To our knowledge, it is a novel impurity and not reported elsewhere.
authors: Analytical Research and Development, United States Pharmacopeial Convention - India (P) Ltd., Plot No. D6 & D8, IKP, Genome Valley, Shameerpet, Hyderabad 500078, India.
authors: Ravi
authors: R
authors: Rapolu
authors: Analytical Research and Development, United States Pharmacopeial Convention - India (P) Ltd., Plot No. D6 & D8, IKP, Genome Valley, Shameerpet, Hyderabad 500078, India.
authors: Ch Krishnam
authors: ChK
authors: Raju
authors: Analytical Research and Development, United States Pharmacopeial Convention - India (P) Ltd., Plot No. D6 & D8, IKP, Genome Valley, Shameerpet, Hyderabad 500078, India.
authors: Kolupula
authors: K
authors: Srinivas
authors: Analytical Research and Development, United States Pharmacopeial Convention - India (P) Ltd., Plot No. D6 & D8, IKP, Genome Valley, Shameerpet, Hyderabad 500078, India. Electronic address: axa@usp.org.
authors: Atul
authors: A
authors: Awasthi
authors: Analytical Research and Development, United States Pharmacopeial Convention - India (P) Ltd., Plot No. D6 & D8, IKP, Genome Valley, Shameerpet, Hyderabad 500078, India.
authors: Sameer G
authors: SG
authors: Navalgund
authors: Analytical Research and Development, United States Pharmacopeial Convention - India (P) Ltd., Plot No. D6 & D8, IKP, Genome Valley, Shameerpet, Hyderabad 500078, India.
authors: Koduru V
authors: KV
authors: Surendranath
mesh_terms: D000143:Acids / Q000737:chemistry; D017311:Amlodipine / Q000032:analysis* / Q000737:chemistry; D000959:Antihypertensive Agents / Q000032:analysis* / Q000737:chemistry; D048588:Benzoxazines / Q000737:chemistry / Q000302:isolation & purification*; D002851:Chromatography, High Pressure Liquid; D018360:Crystallography, X-Ray; D004340:Drug Contamination; D004355:Drug Stability; D009682:Magnetic Resonance Spectroscopy; D008968:Molecular Conformation; D009904:Optical Rotation; D012997:Solvents / Q000737:chemistry; D017550:Spectroscopy, Fourier Transform Infrared; D013237:Stereoisomerism; D014867:Water / Q000737:chemistry
chemical_list: D000143:Acids; D000959:Antihypertensive Agents; D048588:Benzoxazines; D012997:Solvents; C000596630:ethyl-6-(2-chlorophenyl)-8-methyl-3,4,6,7-tetrahydro-2H-benzo(b)(1,4)oxazine-5-carboxylat; D014867:Water; D017311:Amlodipine
keywords: Computational chemistry; LC-HRMS; NMR; Novel impurity of Amlodipine Besylate; Single crystal X-ray