title: Pharmaceutical and analytical characterisation of (2R)-(3-amino-2-fluoropropyl)sulphinic acid, a GABAB receptor agonist.
abstract: (2R)-(3-amino-2-fluoropropyl)sulphinic acid (AFPSiA) is a potent GABAB agonist, which makes it a possible alternative in future GERD treatment. The degradation of AFPSiA was investigated to support the drug-development effort. The compound is too polar to be compatible with regular reversed-phase LC. Moreover, the compound and the degradation products cannot be detected by UV due to low absorption. Instead, the degradation of AFPSiA was followed by two different capillary electrophoresis methods with indirect UV detection and 1H NMR and 19F NMR. AFPSiA was very unstable in basic conditions and at temperatures above room temperature. The corresponding sulphonic acid and allylamine are formed via two separate degradation routes. Both these degradation products may cause unwanted side-effects in vivo. Aqueous solutions of AFPSiA were found to be more stable at pH between 1 and 3. It was suggested that AFPSiA should be stored frozen, preferably at -70 degrees C. In solid state, the compound can be stored at ambient conditions in closed vials with low relative humidity. A solid oral dosage form should be kept in a blister package.
authors.affiliation: Pharmaceutical and Analytical R&D, AstraZeneca R&D Mölndal, Mölndal, Sweden. carl-gustav.sigfridsson@astrazeneca.com
authors.forename: Kalle
authors.initials: K
authors.lastname: Sigfridsson
authors.forename: Thomas
authors.initials: T
authors.lastname: Andersson
authors.forename: Lena
authors.initials: L
authors.lastname: Nilsson
authors.forename: Veronica
authors.initials: V
authors.lastname: Schönbacher
authors.forename: Yudong
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000284:Administration, Oral; D002626:Chemistry, Pharmaceutical; D004304:Dosage Forms; D004349:Drug Packaging; D004355:Drug Stability; D004356:Drug Storage; D019075:Electrophoresis, Capillary / Q000379:methods*; D005615:Freezing; D018755:GABA Agonists / Q000008:administration & dosage / Q000032:analysis / Q000737:chemistry* / Q000494:pharmacology; D058785:GABA-A Receptor Agonists; D006863:Hydrogen-Ion Concentration; D007275:Injections, Intravenous; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D012996:Solutions; D013056:Spectrophotometry, Ultraviolet; D013441:Sulfinic Acids / Q000008:administration & dosage / Q000032:analysis / Q000737:chemistry* / Q000494:pharmacology; D013696:Temperature; D013997:Time Factors
chemical_list: C505962:3-amino-2-fluoropropylsulfinic acid; D004304:Dosage Forms; D018755:GABA Agonists; D058785:GABA-A Receptor Agonists; D012996:Solutions; D013441:Sulfinic Acids