Wong S H
Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Ther Drug Monit. 1993 Dec;15(6):576-80.
Advances have been made in chromatography complement immunoassay for clinical drug analysis. Chromatographic theory shows that the minimum detectable mass is directly proportional to the square of column radius. Small internal diameter columns are capable of analyzing lower analyte concentrations, and high resolution is achievable in open capillary columns, concomitant with greatly reduced mobile phase consumption and waste. This review, based on the author's experience and literature, focuses on supercritical fluid chromatography (SFC), capillary electrophoresis (CE), and selected high-performance liquid chromatography (HPLC) methodologies--microbore and direct-sample analysis (DSA) using commercially available Restricted Access Media (RAM) and REMEDi. In investigating the feasibility of SFC, the "normal-phase-like" selectivity of carbon dioxide was established, affecting the design of the extraction protocol and the elution order of drugs and metabolites. For example, the "more polar" tautomer eluted after FK-506, opposite to the order in the reversed-phase HPLC analysis. CE was investigated by Shihabi et al. for the analysis of pentobarbital and iohexol, while Evenson and Wiktorowicz performed preliminary evaluation of several therapeutic drug monitoring (TDM) drug groups. Innovation in HPLC column technology and hardware have greatly enhanced clinical drug analysis. Microbore column, offering enhanced mass sensitivity and high resolution, utilizes small sample size of 5 microliters of serum for the analysis of chloramphenicol. Commercially available RAM include internal surface reversed phase, shielded hydrophobic phase, and dual zone media, readily applicable for serum drug analysis without any sample preparation. Recently, an automated HPLC REMEDi offers urine and serum drug screening for toxicology.
在临床药物分析的色谱互补免疫分析方面已取得进展。色谱理论表明，最小可检测质量与柱半径的平方成正比。小内径柱能够分析更低的分析物浓度，并且在开放毛细管柱中可实现高分辨率，同时大大减少流动相的消耗和浪费。本综述基于作者的经验和文献，重点关注超临界流体色谱（SFC）、毛细管电泳（CE）以及选定的高效液相色谱（HPLC）方法——使用市售受限 access 介质（RAM）和 REMEDi 的微径柱和直接进样分析（DSA）。在研究 SFC 的可行性时，确定了二氧化碳的“类正相”选择性，这影响了提取方案的设计以及药物和代谢物的洗脱顺序。例如，“极性更强”的互变异构体在 FK - 506 之后洗脱，与反相 HPLC 分析中的顺序相反。Shihabi 等人研究了 CE 用于戊巴比妥和碘海醇的分析，而 Evenson 和 Wiktorowicz 对几个治疗药物监测（TDM）药物组进行了初步评估。HPLC 柱技术和硬件的创新极大地增强了临床药物分析。微径柱具有更高的质量灵敏度和高分辨率，利用 5 微升血清的小样本量来分析氯霉素。市售的 RAM 包括内表面反相、屏蔽疏水相和双区介质，无需任何样品制备即可轻松应用于血清药物分析。最近，一种自动化的 HPLC REMEDi 提供用于毒理学的尿液和血清药物筛查。
