Capillary Electrophoresis for Drug Analysis in Body Fluids

Abstract

Capillary zone electrophoresis (CZE) and micellar electrokinetic capillary chromatography (MECC) represent attractive methods for the determination of drugs and metabolites in body fluids. In CZE, minute (nanoliter) quantities of samples are applied to the beginning of a fused-silica capillary filled with buffer. On application of a high-voltage DC field, charged solutes begin to separate and are swept through the capillary by the combined action of electrophoresis and electroosmotic bulk flow and are on-column detected toward the capillary end. In MECC, the buffer contains charged micelles (e.g., dodecyl sulfate micelles) and both uncharged and charged solutes separate based on differential partitioning between the micelles and the surrounding buffer and, if charged, also by differential charge effects, including electrophoresis. Based on validated MECC drug assays developed in our laboratory, key aspects of measuring drug levels by MECC, including sample preparation, solute detection and identification, quantitation, reproducibility, and quality assurance are discussed. Drug levels determined by MECC are shown to be in good agreement with those obtained by nonisotopic immunoassays and/or high-performance liquid chromatography (HPLC). Using on-column multi-wavelength detection, this technology is also well suited for toxicological drug screening and confirmation and for the exploration of drug metabolism. Compared with HPLC and gas chromatography, capillary electrophoresis has distinct advantages, including automation, small sample size, minimal sample preparation, use of very small amounts of organic solvents and inexpensive chemicals, ease of buffer change and method development, and low cost of capillary columns. Electrokinetic capillary assays are complementary to the widely employed immunoassays. The state of the art and the pros and cons of capillary electrophoresis for the determination of drugs in body fluids are discussed with the goal of encouraging newcomers to start using this emerging analytical methodology.

Therapeutic drug monitoring of albendazole: Determination of albendazole, albendazole sulfoxide, and albendazole sulfone in human plasma using nonaqueous capillary electrophoresis

“…Most methods, however, are unable to efficiently determine all three compounds simultaneously. Recently, capillary electrophoresis (CE) [11] proved to be a powerful alternative to chromatographic techniques in the analysis of drugs and some of their metabolites in body fluids [12,13]. The main advantages of CE are high separation efficiency, short analysis time, and low operational cost.…”

Micellar electrokinetic capillary chromatography as a powerful tool for pharmacological investigations without sample pretreatment: A precise technique providing cost advantages and limits of detection to the low nanomolar range

“…In the above-mentioned earlier works, high mmolar levels have been determined with reproducibilities in the range of about 2±5% for repeatability (n & 10) and of about 4± 12% for interday precision, respectively ( [2,26], reviews in [11,30,31]; compare Table 13). Generally, CE suffers from a relatively low concentration sensitivity.…”

Capillary electrophoresis in anti‐cancer metallodrug research: Advances and future challenges

“…It was found out that the kinetics of the interactions is strongly correlated to the hydrolysis rate of cisplatin. As the major adducts, [Pt(NH 3 ) 2 (N7-GMP) 2 ] 22 and [Pt(NH 3 ) 2 (N7-AMP) 2 ] 22 were identified, though resulted from interactions with thymidine 5'-monophosphate (TMP) and cytidine 5'-monophosphate (CMP) were only trace adduct peaks that remained for this reason unidentified. The results of competitive studies shown in Fig.…”

“…In order to add an extra selectivity dimension to CE data, the effect of Met on the binding of oxaliplatin to GMP was explored by means of a hyphenated CE-ESI-MS system [46]. Without Met the main reaction product was the bis-GMP adduct (as described in Section 5.1), whereas Met forced [Pt(Dach)(GMP) 2 ] 22 to enter a ligand-exchange reaction producing, along with the major adduct, [Pt(Dach)(Met-S,N)]…”