Methods In Pharmaceutical Analysis Research Articles

Advances in automation of pharmaceutical analysis

The development of a new drug substance and its dosage forms demands the establishment and implementation of suitable analytical methods. Through the application of chemometrics, “intelligent” laboratory systems and integrated data handling systems, considerable progress is being made in automating both the development and routine use of analytical methods in pharmaceutical analysis.

Expert system for the selection of high-performance liquid chromatographic methods in pharmaceutical analysis : Validation of the rules for the selection of the mobile phase

The rules for the selection of the mobile phase and the validation performed on 44 pharmaceutical preparations, containing one to five active compounds, are described. These rules are incorporated into an expert system, called LABEL, for the selection of high-performance liquid chromatographic methods in pharmaceutical analysis. A single stationary phase type is used, namely a nitrile or cyanopropyl (CN) column, which can be used in both normal-phase (NP) and reversed-phase (RP) chromatography. Three mobile phase systems were evaluated on this column type: NP, RP with water and RP with buffer. LABEL selects one of these three systems on the basis of the rules incorporated for the mobile phase selection, checks if the addition of ion-suppressing agents to the eluting agent is necessary and finally gives the starting composition of the mobile phase in each of the three systems. For this selection the number of compounds in the sample, the acid-base properties and the hydrophobicity of the solutes are the more important factors. The validation of the rules on 44 pharmaceutical preparations resulted in an immediate success in 82% of all cases. In half of the remaining cases, the system proposed can be adapted with a minor change in conditions, so that it can be used in practice.

Selection of high-performance liquid chromatographic methods in pharmaceutical analysis : II. Optimization for selectivity in normal-phase systems

Optimization of selectivity in normal-phase chromatography was studied. Using the same optimization criteria ( R s,min , D min, R sb and R sa ) as in Part I the possible combination of “solvent strength” optimization by variation of the percentage of polar modifier in the less polar mobile phase and “solvent type” optimization by measuring the solvent selectivity of chloroform, acetonitrile, tetrahydrofuran and dioxane was examined. From the results it can be concluded that by replacement of medium-polarity solvents (chloroform, acetonitrile, tetrahydrofuran and dioxane) in the mobile phase, the selectivity of the separation can be significantly improved as the elution order is a function of solvent type belonging to Class P. In the separation of a steroid mixture dioxane provides the best properties for improving band spacing.

Selection of high-performance liquid chromatographic methods in pharmaceutical analysis : I. Optimization for selectivity in reversed-phase chromatography

The application of solvent optimization to the development of isocratic reversed-phase liquid chromatography has been reported in several publications. Two different approaches to solvent optimization for controlling band spacing for the maximum resolution of samples are “solvent strength” and “solvent type” optimization. To improve the separation selectivity further the combination of these two approaches was examined, as a (global) optimum mobile phase composition requires the optimization of the solvent strength by varying the percentage of organic component and of the solvent selectivity of methanol, acetonitrile, tetrahydrofuran and water. It was found that the combination of “solvent strength” and “solvent type” optimization provides a markedly better separation than either procedure alone.