Optimisation and characterisation of silica-based reversed-phase liquid chromatographic systems for the analysis of basic pharmaceuticals

Reversed-phase liquid chromatography using silica-based columns is successfully applied in many separations. However, also some drawbacks exist, i.e. the analysis of basic compounds is often hampered by ionic interaction of the basic analytes with residual silanols present on the silica surface, which results in asymmetrical peaks and irreproducible retention. In this review, options to optimise the LC analysis of basic pharmaceutical compounds are discussed, i.e. eluent optimisation (pH, silanol blockers) and stationary phase optimisation (development of new columns with minimised ionic interactions). The applicability of empirical based, thermodynamically based and test methods based on a retention model to characterise silica-based reversed phase stationary phases, as well as the influence of the eluent composition on the LC analysis of basic substances is described. Finally, the applicability of chemometrical techniques in column classification is shown. (C) 2000 Elsevier Science BN. All rights reserved.</p

Characterisation of reversed-phase liquid chromatography stationary phases for the analysis of basic pharmaceuticals: eluent properties and comparison of empirical test methods

The reversed-phase liquid chromatographic analysis of basic pharmaceuticals can be problematic. Both the properties of the eluent and the stationary phase can influence the chromatographic performance. Therefore selection of suitable experimental conditions for the analysis of basic compounds can be difficult. This paper shows that the organic modifier and the nature of the buffer influence the eluent properties. Moreover, the nature and amount of modifier also influence the basicity of the analytes. Investigations showed that the nature of the buffer can have a significant influence on retention and peak shape of basic compounds. Test procedures using basic analytes as test probes provided relevant information with respect to selecting columns to analyse basic pharmaceutical compounds. Test procedures using compounds like aniline, phenol and benzene were found to be less suitable. (C) 2001 Published by Elsevier Science B.V

Characterisation of reversed-phase stationary phases for the liquid chromatographic analysis of basic pharmaceuticals by thermodynamic data

This paper describes the characterisation of reversed-phase liquid chromatography (RPLC) columns using thermodynamic measurements. Retention versus I IT data were used to construct Van't Hoff plots. The slope of these plots indicates the standard enthalpy of transfer of the analyte from the mobile to the stationary phase. The standard entropy can be calculated from the intercept. Van't Hoff plots were linear for the investigated RPLC columns, meaning that for basic analytes over the temperature range studied no changes in the retention mechanism occurred. Enthalpies and entropies of transfer of basic analytes from the mobile to the stationary phase revealed information about the types of interaction of protonated and neutral compounds with the stationary phases. However. a clear view using the present set of basic compounds on how these thermodynamic data may explain the observed substantial differences in peak symmetry cannot be given, It is considered that addition of N,N-dimethyloctylamine (DMOA) to the eluent will results in a dynamically coating of the stationary phase. Addition of DMOA to the eluent resulted for protonated basic compounds in a reduction of both enthalpy and entropy. In practice, with DMOA in the eluent symmetrical peaks were obtained. It is assumed that this is due to blocking residual silanols and/or ion exclusion effects. (C) 2002 Elsevier Science B.V. All rights reserved

Influence of batch-to-batch reproducibility of Luna C-18(2) packing material, nature of column wall material, and column diameter on the liquid chromatographic analysis of basic analytes

This paper discusses aspects arising on transferring liquid chromatography (LC) methods developed on conventional size columns to micro LC, i.e. the influence of batch-to-batch reproducibility of packing material, the nature of the column wall material, and the column inner diameter. it was shown that the nature of the column hardware as well as batches of Luna C18(2) packing material did not influence the retention of basic compounds. The batches of packing material, however, significantly influenced the peak shape for some compounds. The nature of the mobile phase buffer also showed an effect on peak shape. The column wall material as well as the column inner diameter did not reveal effects on the peak shape. Different packing densities were found for micro and conventional LC columns, i.e. the micro LC columns were less densely packed than the conventional LC columns. The study demonstrated that for the analysis of basic analytes similar separations are obtained using micro and conventional LC columns provided that the columns are packed from the same batch of packing material