Elimination of adsorption effects in the analysis of water-soluble vitamins in pharmaceutical formulations by capillary electrophoresis.

A tendency to an increase in migration times was observed when different water-soluble vitamins were analysed repeatedly in pharmaceutical preparations by capillary electrophoresis. In order to better understand the origin of this effect, the influence of the vitamins and the excipients, such as cellulose derivatives, was investigated. These studies indicated that the increase in analyte migration times was most probably due to the adsorption of different kinds of constituents to the capillary wall. Different rinsing procedures were tested in order to eliminate these unfavourable effects. A rinse of the capillary with a 25 mM sodium dodecyl sulfate (SDS) solution in the running buffer between successive runs was found to be particularly effective when the analysis was performed by free solution capillary zone electrophoresis (CZE). When the vitamins were determined by micellar electrokinetic chromatography (MEKC) using SDS as surfactant, a short capillary rinse with the running buffer was sufficient to obtain reproducible migration times. The CZE and MEKC methods developed were validated and compared. Both methods could be applied to the determination of water-soluble vitamins in different multivitamin formulations.

Stereoselective determination of S-naproxen in tablets by capillary electrophoresis.

A capillary electrophoresis (CE) method was developed for the stereoselective determination of the non-steroidal anti-inflammatory drug (NSAID), S-naproxen, in tablets. Several beta-cyclodextrin derivatives (CDs) were tested as chiral selectors, including sulfobutyl-beta-CD (SBCD), carboxymethyl-beta-CD (CMCD), dimethyl-beta-CD (DMCD) and trimethyl-beta-CD (TMCD), in a phosphoric acid/triethanolamine pH 3 buffer. Under these conditions, the analyte was mainly present in an uncharged form and therefore, the use a neutral CD (DMCD or TMCD) alone could not lead to enantiomeric separation. On the contrary, by addition of a charged CD (SBCD or CMCD) to the running buffer, giving the analyte enantiomers an adequate mobility, chiral resolution could be achieved, although the resolution values obtained in this case were not quite satisfactory (Rs < 1.5). Dual systems, based on the use of mixtures of charged and neutral CDs, were then investigated. The SBCD/TMCD system was found to be particularly well suited to the enantioseparation of naproxen and after optimisation of the concentrations of both CDs, a resolution value of 5.4 could be obtained. The method was validated for the determination of R-naproxen (enantiomeric impurity) in the 0.1-2% range, using the racemic mixture of the analyte. A second validation was performed in the 50-150% range for the quantitation of S-naproxen. In both cases, good results with respect to linearity, precision and accuracy were obtained.

Determination of six water-soluble vitamins in a pharmaceutical formulation by capillary electrophoresis.

A method was developed for the quantitative analysis of six water-soluble vitamins (thiamine, nicotinamide, riboflavine, pyridoxine, ascorbic acid and pantothenic acid) in a pharmaceutical formulation, using free solution capillary zone electrophoresis (CZE) in uncoated fused silica capillaries and UV detection. The influence of different parameters, such as the nature of the buffer anionic component and buffer concentration on the CZE separation of vitamins was investigated using four vitamins of the B group as model compounds. A good compromise between resolution, analysis time and analyte stability was obtained by use of a 50 mM borax buffer of pH 8.5. This CZE method was found to be very useful for the separation of more complex samples, a mixture of ten water-soluble vitamins being completely resolved in about 10 min. However, cyanocobalamine could not be separated from nicotinamide in this CZE system, the two compounds being in uncharged form at the pH used. These two compounds could easily be resolved by micellar electrokinetic chromatography (MEKC), the anionic surfactant dodecylsulfate being added to the running buffer at 25 mM concentration. In the pharmaceutical formulation, some excipients were found to be adsorbed to the capillary surface, giving rise to a progressive decrease of the electroosmotic flow and consequently to a simultaneous increase of analyte migration times. A capillary wash with sodium hydroxide had to be made between successive runs in order to minimize these effects. Good results with respect to linearity, precision and accuracy were obtained in the concentration range studied for the six vitamins, using nicotinic acid as internal standard.