Capillary electrophoresis in the pharmaceutical industry: applications in discovery and chemical development.

Over the last 10 to 15 years capillary electrophoresis (CE) has become an extensively used separation technique in the pharmaceutical industry. The attraction of the various modes of operation of CE to analysts is their complementarity to other more established methodology, in particular high-performance liquid chromatography. CE methods have been developed not only for the resolution of drug substances that vary widely in their structure, size and stereochemistry, but also for the determination of the physico-chemical constants of analytes, such as pKa and isoelectric point (pI) values, binding and complexation constants, and octanol-water partition coefficients.

PH-metric log P 11. pKa determination of water-insoluble drugs in organic solvent-water mixtures.

The apparent acid dissociation constants (p(s)Ka) of two water-insoluble drugs, ibuprofen and quinine, were determined pH-metrically in acetonitrile water, dimethylformamide water, dimethylsulfoxide water, 1,4-dioxane-water, ethanol water, ethylene glycol-water, methanol water and tetrahydrofuran water mixtures. A glass electrode calibration procedure based on a four-parameter equation (pH = alpha + SpcH + jH[H+]+jOH[OH-]) was used to obtain pH readings based on the concentration scale (pcH). We have called this four-parameter method the Four-Plus technique.

Resolution of the diastereomers of a large synthetic peptide by capillary electrophoresis using nonionic surfactants.

A capillary electrophoretic method was developed for the determination of the diastereomeric composition of the bradykinin B2 antagonist, SB-238592-DB. The nonionic surfactant Brij 35 was demonstrated to be suitable for the baseline resolution of the three diastereoisomers of SB-238592-DB in the presence of a low pH phosphate buffer and small volume percentages of acetonitrile.

Capillary electrophoresis of DNA restriction fragments with solutions of entangled polymers.

Separation of DNA restriction fragments in dilute buffer solutions of network forming polymers such as linear polyacrylamide (PAA), hydroxyethyl cellulose (HEC) and polyvinylalcohol (PVA) in phosphate buffer were investigated. PVA in buffers already became inhomogeneous after a few separations with resultant deterioration of resolution. Hydroxylic polymers, capable of forming suitable networks in buffers, are strongly adsorbed to fused silica surfaces suppressing the electroosmotic flow.