title: Development of a semi-automated chemical stability system to analyze solution based formulations in support of discovery candidate selection.
abstract: A semi-automated chemical stability system was developed, validated, and implemented to assess the chemical and physical stability (24 h) of intravenous and oral solution based formulations in support of preliminary in vivo drug discovery studies. The system utilizes a single Agilent 1100 LC and Xterra column with multiple UV wavelength monitoring. Mobile phase selection, either basic or acidic, is selected base upon on the physico-chemical properties of the test compound. The system was validated against 14 new chemical entities across multiple therapeutic areas. The results indicated that drug discovery compounds could be accurately quantified (<2% R.S.D.) in a wide range of formulation vehicles in greater than 90% of the test cases. This method can be used as a quantitative tool for triaging formulation variables and packaging configurations to quickly develop stable solutions for dosing.
authors.affiliation: Pharmaceutical Sciences, Pfizer Global Research and Development, 2800 Plymouth Road, Ann Arbor, MI 48105, USA.
authors.forename: Linda
authors.initials: L
authors.lastname: Hitchingham
authors.forename: V Hayden
authors.initials: VH
authors.lastname: Thomas
mesh_terms: D001322:Autoanalysis / Q000379:methods; D002626:Chemistry, Pharmaceutical; D002853:Chromatography, Liquid / Q000379:methods*; D004355:Drug Stability; D016014:Linear Models; D004364:Pharmaceutical Preparations / Q000032:analysis / Q000737:chemistry*; D015203:Reproducibility of Results; D012996:Solutions; D012997:Solvents / Q000737:chemistry; D013056:Spectrophotometry, Ultraviolet / Q000379:methods*; D013678:Technology, Pharmaceutical / Q000379:methods*; D013997:Time Factors
chemical_list: D004364:Pharmaceutical Preparations; D012996:Solutions; D012997:Solvents