Basic Drug Analysis


Ever since we introduced the first ground-breaking P/ACE™ system in 1989, we have led the industry in CE technology. Our developments encompass hardware, software and chemistry, with a long list of technology advancements that include laser-induced fluorescence, diode array detection, and advanced CE data reduction. Always directed by your feedback, we continue to focus on leadership, and on new ways to apply the core technology to key analytical solutions.

Basic Drug Analysis

While the highly polar nature of basic pharmaceuticals makes chromatography complex, CE has the ability to excel at such separations.

The graph shows the analysis of 20 basic drugs using low pH, where the capillary surface is essentially neutral and the amine functional groups on the solutes are maximally ionized. The robust nature of this tool and the ruggedness of this particular approach are appropriate for screening protocols used in drug discovery and forensic toxicology.

Indeed, the highly polar nature of pharmaceuticals containing basic amine functionalgroups makes the use of chromatography quite complex. Ion pairing reagents and stringent column regeneration is often necessary to reduce nonspecific ionic interactions that occur with reverse-phase chromatography.

With CE, these highly functional amines are favored and may be exploited to provide extraordinary resolution. The most common and simplified format of operation is to use bare-fused silica capillaries at a well defined acidic pH. Under these conditions the capillary surface is essentially non-reactive while an analyte's amine functional groups are maximally ionized, rendering a simplified robust assay for the analysis of basic drugs. The P/ACE™ MDQ, coupled with photo-diode array detection, is being used for this application, and is being applied effectively in the pharmaceutical industry for the analysis of basic drugs, pharmokinetic profiling, bioavailability determinations, plasma protein binding studies and drug activity level determination.

One of the challenges of drug discovery is in developing analytical methods for the pharmacokinetic (PK) profiling of new drug candidates. Important to this process is the development of rapid, generic methods that allow the screening of large numbers of compounds isolated from complex sample matrices. CE is being used routinely to quantify drugs in blood plasma, as well as in brain, kidney and heart tissue. The high efficiency and the lack of interference from the matrix make CE a fast and easy analytical tool for PK screening. A derivative of this application is also being used for screening drugs of toxicological interest, enabled by combining an analytes spectral signature with its electrophoretic mobility to provide highly reproducible identification.

Additionally, because of its unique abilities, CE has been successfully applied in forensic toxicology for basic drug screening.

  

Technical Document