Mass spectrometry-compatible ICH (International Conference on Harmonization) impurity analysis with a high-pH mobile phase: Advantages and pitfalls

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...

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Bibliographic Details
Published in:Journal of Chromatography A 2003-02, Vol.987 (1), p.283-290
Main Authors: Dong, M.W, Miller, G.D, Paul, R.K
Format: Article
Language:English
Subjects:
Analysis
Biological and medical sciences
General pharmacology
Hydrogen-Ion Concentration
Mass Spectrometry - methods
Medical sciences
Pharmacology. Drug treatments
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Summary: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.
ISSN:0021-9673
DOI:10.1016/S0021-9673(02)01961-1