Measurement of dissociation constants (pKa values) of organic compounds by multiplexed capillary electrophoresis using aqueous and cosolvent buffers.

Evaluation of a multiplexed capillary electrophoresis (CE) method for pK(a) measurements of organic compounds, including low solubility compounds, is presented. The method is validated on a set of 105 diverse compounds, mostly drugs, and results are compared to literature values obtained from multiple references. Two versions of the instrument in two different labs were used to collect data over a period of 3 years and inter-laboratory and inter-instrument variations are discussed.

Rapid pKa estimation using vacuum-assisted multiplexed capillary electrophoresis (VAMCE) with ultraviolet detection.

A rapid approach for estimating the pK(a) value of small organic molecules was developed using vacuum-assisted multiplexed capillary electrophoresis (VAMCE) with ultraviolet detection. The VAMCE method employed a 96-capillary array, arranged in a standard 8 x 12 microtiter plate configuration, with each row of capillaries filled with 12 individual running buffers of equal ionic strength (I = 50 mM) covering a pH range from 2.2 to 10.

High-throughput multiplexed capillary electrophoresis in drug discovery.

The demand for high-throughput analytical tools to support drug discovery applications has led to the development of multiplexed capillary electrophoresis and multichannel microfluidic devices to characterize libraries of compounds and alleviate backlogs in the discovery process. The capability to analyze multiple samples in parallel, and the diverse separation conditions that are permissible, facilitates rapid turnaround times. Examples of high-throughput applications of multiplexed electrophoresis in drug discovery include: physicochemical profiling, enzyme analysis, chiral separations and protein/metabolite analysis.

High-throughput characterization and quality control of small-molecule combinatorial libraries.

To fully realize the potential of combinatorial synthesis and high-throughput screening for increasing the efficiency of the drug discovery and development process, issues related to compound purity must be addressed. Impurities, often present after synthesis, can lead to ambiguous screening results and inhibit the development of quality structure-activity relationships. The demand for high-throughput analytical characterization of combinatorial libraries has prompted the development of more rapid methods to keep pace with compound production.

Techniques for high-throughput characterization of peptides, oligonucleotides and catalysis efficiency.

Combinatorial processes have been widely applied to many disciplines in chemistry and biology. The vast numbers of unique entities generated by combinatorial synthesis have led to the development of high-throughput methods for characterizing samples, to avoid bottlenecks created by the application of conventional, serial-based analytical techniques. In recent years, high-throughput and novel methods utilizing mass spectrometry, multiplexed capillary electrophoresis, various forms of optical detection, and even sound waves have been investigated for a variety of applications.

Validation and long-term assessment of an approach for the high throughput determination of lipophilicity (log POW) values using multiplexed, absorbance-based capillary electrophoresis.

A critical evaluation of the use of 96-capillary multiplexed microemulsion electrokinetic chromatography (MMEEKC) for the indirect determination of octanol-water partition coefficients (log POW values) for a wide range of structurally different compounds is presented. The various components of the microemulsion solution were evaluated and optimized for use in a multiplexed capillary format. A six-component calibration mixture and 23 different solutes (n = 4 each) were analyzed simultaneously, providing a throughput of up to 46 samples/h, which translates to greater than a 20-fold improvement over existing indirect log POW methods.