title: Mass spectrometry-compatible ICH (International Conference on Harmonization) impurity analysis with a high-pH mobile phase advantages and pitfalls.
abstract: Recent advances in bonding chemistry and novel silica synthesis have significantly extended the pH range of silica-based HPLC columns. This extended range now enables the analysis of water-soluble basic drugs at high pH without ion-pairing reagents, thus offering an alternative approach to assay or impurity analyses. This paper describes the many advantages and potential pitfalls of using high-pH mobile phases in the development of MS-friendly LC gradient impurity analytical methods for water-soluble basic drugs under International Conference on Harmonization (ICH) guidelines. Operating at high-pH provides excellent peak shapes and retention, and accentuates selectivity differences of structurally similar impurities and degradants. However, several problems unique to the use of high-pH mobile phases, such as column lifetime, robustness of pH adjustments, peak fronting, and on-column dimerization, were encountered. Each of these problems is discussed with its respective remedy.
authors.affiliation: Purdue Pharma, L.P., 444 Saw Mill River Road, Ardsley, NY 10502, USA. michael.dong@pharma.com
authors.forename: M W
authors.initials: MW
authors.lastname: Dong
authors.forename: G D
authors.initials: GD
authors.lastname: Miller
authors.forename: R K
authors.initials: RK
authors.lastname: Paul
mesh_terms: D006863:Hydrogen-Ion Concentration; D013058:Mass Spectrometry / Q000379:methods*