Development of a semi-automated chemical stability system to analyze solution based formulations in support of discovery candidate selection

• Published in: Journal of pharmaceutical and biomedical analysis Vol. 43; no. 2; pp. 522 - 526
• Main Authors: Hitchingham, Linda, Thomas, V. Hayden
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 17.01.2007; Elsevier Science
• Subjects: Analysis; Analytical, structural and metabolic biochemistry; Autoanalysis - methods; Biological and medical sciences; Chemical stability; Chemistry, Pharmaceutical; Chromatography, Liquid - methods; Discovery formulation; Drug Stability; Fundamental and applied biological sciences. Psychology; General pharmacology; Generic analytical method; Linear Models; Medical sciences; Pharmaceutical Preparations - analysis; Pharmaceutical Preparations - chemistry; Pharmacology. Drug treatments; Pre-clinical development; Reproducibility of Results; RP-LC; Solutions; Solvents - chemistry; Spectrophotometry, Ultraviolet - methods; Technology, Pharmaceutical - methods; Time Factors; Discovery formulation; Generic analytical method; Chemical stability; RP-LC; Pre-clinical development; Automation; Formulation; Analytical method; Development; Generic drug
• ISSN: 0731-7085; 1873-264X
• DOI: 10.1016/j.jpba.2006.08.004

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.