ADVANCES IN CHROMATOGRAPHY FOR CLINICAL DRUG ANALYSIS - SUPERCRITICAL-FLUID CHROMATOGRAPHY, CAPILLARY ELECTROPHORESIS, AND SELECTED HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHY TECHNIQUES

Advances have been made in chromatography complement immunoassay for c linical drug analysis. Chromatographic theory shows that the minimum d etectable mass is directly proportional to the square of column radius . Small internal diameter columns are capable of analyzing lower analy te concentrations, and high resolution is achievable in open capillary columns, concomitant with greatly reduced mobile phase consumption an d waste. This review, based on the author's experience and literature, focuses on supercritical fluid chromatography (SFC), capillary electr ophoresis (CE), and selected high-performance liquid chromatography (H PLC) methodologies-microbore and direct-sample analysis (DSA) using co mmercially available Restricted Access Media (RAM) and REMEDi. In inve stigating the feasibility of SFC, the ''normal-phase-like'' selectivit y of carbon dioxide was established, affecting the design of the extra ction protocol and the elution order of drugs and metabolites. For exa mple, the ''more polar'' tautomer eluted after FK-506, opposite to the order in the reversed-phase HPLC analysis. CE was investigated by Shi habi et al. for the analysis of pentobarbital and iohexol, while Evens on and Wiktorowicz performed preliminary evaluation of several therape utic drug monitoring (TDM) drug groups. Innovation in HPLC column tech nology and hardware have greatly enhanced clinical drug analysis. Micr obore column, offering enhanced mass sensitivity and high resolution, utilizes small sample size of 5 mul of serum for the analysis of chlor amphenicol. Commercially available RAM include internal surface revers ed phase, shielded hydrophobic phase, and dual zone media, readily app licable for serum drug analysis without any sample preparation. Recent ly, an automated HPLC REMEDi offers urine and serum drug screening for toxicology.