Potential of packed column supercritical fluid chromatography for the separation of metoprolol from closely related compounds

Using the present SFC method metoprolol can be separated from 12 analogues and related compounds within 12 min. It is also possible to detect most of these analogues at the 0.1% (w/w) level when added to the pure drug substance. The method is based on SFC with modified carbon dioxide as the mobile phase and a packed 4 mm I.D. diol-modified silica column. The mobile phase modifier is 10% (v/v) methanol containing 0.35 M of acetic acid and 0.07 M of triethylamine. UV detection is performed at 273 nm. The main advantage with the described method over the currently used reversed-phase liquid chromatographic method is the different selectivity, i.e., it is possible to separate and detect isomers that elute close to the metoprolol peak in currently used liquid chromatographic systems. (C) 1999 Elsevier Science B.V. All rights reserved.