Analysis of basic antimalarial drugs by CZE; Part 2. Validation and application to bioanalysis

Area of Science:

• Analytical Chemistry
• Separation Science
• Pharmacokinetics

Background:

• Capillary electrophoresis (CE) and micellar electrokinetic chromatography (MEKC) are advanced separation techniques.
• Proguanil and chloroquine are important antimalarial drugs with known metabolites.
• Quantitative analysis of these compounds in biological matrices presents challenges.

Purpose of the Study:

• To quantitatively assess the CZE separation of proguanil, chloroquine, and their metabolites.
• To evaluate the precision of migration time and peak areas using different injection methods.
• To report the limits of detection (LOD) for these compounds in urine using optimized methods.

Main Methods:

• Capillary Zone Electrophoresis (CZE) and Micellar Electrokinetic Chromatography (MEKC) were employed.
• Vacuum and electrokinetic injection techniques were compared for precision.
• Solid Phase Extraction (SPE) was used for sample pretreatment.
• Assay validation parameters were determined for urine analysis.

Main Results:

• Electrokinetic injection with an organic solvent significantly increased concentration sensitivity.
• Improved limits of detection for proguanil, chloroquine, and metabolites in urine were achieved.
• The precision of migration time and peak areas was evaluated for both injection methods.
• Limitations of the SPE method for plasma and saliva matrices were identified.

Conclusions:

• Electrokinetic injection offers enhanced sensitivity for CZE/MEKC analysis of proguanil and chloroquine metabolites.
• The developed assay method, including SPE, is suitable for quantifying these drugs in urine.
• Further optimization is needed for analyzing complex biological matrices like plasma and saliva.