High-performance liquid chromatography of timolol and potential degradates on dynamically modified silica
1Department of Pharmaceutical Research and Development, Merck Sharp & Dohme Research Laboratories, West Point, PA 19486.
Abstract:
A novel method for the determination of timolol in pharmaceutical products has been developed and is described. The method employs high-performance liquid chromatography (HPLC) on silica dynamically modified with the cetyltrimethylamomonium cation to quantitate the analyte. The use of this type of reversed-phase HPLC system for timolol determinations results in improved quality of chromatography, especially in terms of peak tailing and peak efficiency, in comparison to chromatography on bonded-phase silica. Column-to-column as well as manufacturer-to-manufacturer reproducibility for this separation on silica columns has been obtained and is better in our hands than that encountered with bonded-phase column packings. The method has been shown to be linear for the compounds studied, comparably accurate and precise to bonded-phase methods and specific for timolol in a variety of pharmaceutical formulations. Under the conditions specified, timolol can be successfully separated from its three potential degradates. Possible explanations of the primary retention mechanisms for the analytes are offered.
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