Preliminary study on the effect of miniaturisation and use of volatile mobile phases in LC for the on-line LC-MS analysis of basic pharmaceuticals

To enhance to compatibility of the on-line coupling of liquid chromatograph y (LC) with mass spectrometry (MS) for the analysis of basic pharmaceutical s, the use of volatile mobile phase systems in combination with miniaturise d LC was investigated. Multifactor analysis of variance (MANOVA) was used t o evaluate the data obtained for the various variables (modifier, stationar y phase, buffer, buffer pH and buffer concentration) on the resolution, pea k symmetry and retention of four basic compounds analysed using LC columns with internal diameters (I.D.) of 0.3, 1.0 and 4.6 mm (conventional). Preli minary results obtained with the investigated micro and conventional column s showed similar behaviour with respect to ruggedness. The various investig ated variables showed that miniaturisation by simply downscaling dimensions can result in varying selectivity and peak shapes for basic compounds. Whe n comparing volatile mobile phases (containing ammonium acetate or ammonium citrate) and a conventional non-volatile mobile phase (containing sodium p hosphate) under pH 3 conditions, similar separation performances were obser ved. In the present study, ammonium citrate as the buffering salt, a high b uffer concentration and methanol as the modifier showed the best peak symme try. (C) 1999 Elsevier Science B.V. All rights reserved.