Use of capillary electrophoresis methods to characterize the pharmacokinetics of antisense drugs.
As antisense drugs become mature for clinical trials, analytical techniques to analyze antisense DNA in biological media for characterization of their pharmacokinetics will be in demand. Due to the superior resolving power of capillary gel electrophoresis (CGE), CGE will likely be a preferred method in quantifying intact oligonucleotides as well as the putative metabolic products. Nonetheless, biological mediums can influence the stability of the gel column, making a CGE assay time-consuming. In one approach, high-performance liquid chromatography (HPLC) was used to quantify the total amount of antisense compounds to increase the sample throughput and CGE was used to determine the relative percentage of the intact and metabolic species on specific samples. Alternatively, extensive sample pretreatment procedures were performed and the samples were quantified and characterized directly by CGE alone with the use of an internal standard. Both methods have been used to characterize the pharmacokinetics of antisense compounds. This review focuses on the instrumental and technical aspects of analyzing antisense DNA in biological mediums using CGE either as a single or a combined method towards better understanding of the pharmacokinetics of antisense DNA. Moreover, the newer analytical technologies of capillary electrophoresis (CE), which hold great potential to be used for pharmacokinetic applications, such as the replenishable sieving matrix combined with an innovative coupling approach and microchip CE, will also be explored.
Chen
S H
SH
Department of Chemistry, National Cheng Kung University, Tainan, Taiwan. shchen@mail.ncku.edu.tw
Gallo
J M
JM
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D016373:DNA, Antisense / Q000302:isolation & purification / Q000493:pharmacokinetics*; D019075:Electrophoresis, Capillary / Q000379:methods*; D006801:Humans
D016373:DNA, Antisense