Monolithic stationary phase coupled with coulometric detection: development of an ion-pair HPLC method for the analysis of quinone-bearing compounds.
Memoquin, a recently discovered new drug candidate for the treatment of Alzheimer's disease (AD), is a compound able to interfere with different key targets of AD neurodegeneration. In the present work, the electroactivity of Memoquin, due to the presence of a quinone ring in the molecule, was exploited for the development of a sensitive and selective HPLC chromatographic method with coulometric detection system. For this purpose, a monolithic silica-based stationary phase (Chromolith C18) was coupled with ESA detector and under high flow rate condition (2 mL/min) gave an efficient coulometric detection without a significant backpressure. The monolithic stationary phase and the electrochemical detection were combined to obtain a very fast (less than 7 min) and sensitive analysis of the compound of interest. For this reason, the method was found suitable to determine Memoquin with very high sensitivity (LOD, 0.005 microg/mL; LOQ, 0.016 microg/mL), better than with UV and fluorescence detections, and selectivity resulting potentially suitable for its analysis in biological samples. Moreover, the HPLC method was employed for the separation of Memoquin from other quinone analogs (endowed with different substituent on the quinone ring and length of the lateral chain) and allowed the comparison of the electrochemical properties of the compounds of the series. In the optimized chromatographic conditions it was possible to separate each quinone and to evaluate the influence of the substituent of the quinone ring on the electrochemical properties of the molecule.
Mancini
Francesca
F
Department of Pharmaceutical Sciences, University of Bologna, Bologna, Italy.
Bolognesi
Maria L
ML
Melchiorre
Carlo
C
Cavalli
Andrea
A
Andrisano
Vincenza
V
D000473:Alkanes / Q000032:analysis*; D002851:Chromatography, High Pressure Liquid / Q000295:instrumentation / Q000379:methods; D004563:Electrochemistry; D005021:Ethylamines / Q000032:analysis*; D015394:Molecular Structure; D011809:Quinones / Q000032:analysis*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D012822:Silicon Dioxide / Q000737:chemistry; D013499:Surface Properties; D013997:Time Factors
D000473:Alkanes; D005021:Ethylamines; D011809:Quinones; C521476:memoquin; D012822:Silicon Dioxide