Sternson L A
Xenobiotica. 1987 Mar;17(3):385-96. doi: 10.3109/00498258709043946.
The sensitivity and selectivity achievable in the analysis of drug substances from biological matrices is often limited by the physical and chemical properties of the analyte. These limitations are further exacerbated by the inherent reactivity of most drugs in biological systems (i.e., their propensity for undergoing biotransformation). One very powerful approach that has been taken to improve the quality of the analytical methodology is to alter the physico-chemical properties of the drug through chemical modification (derivatization) during some stage of the analytical sequence. This approach has been successfully applied to situations and has resulted in improved chemical stability, analytical selectivity and sensitivity. In most cases, drug analysis from biological fluids involves a chromatographic step; the derivatization reaction can be carried out either prior or subsequent to chromatography. In this paper, examples of the advantages (and limitations) offered by the introduction of a chemical derivatization step in clinical drug analysis will be presented. Specifically, focus will be placed on analysis of chemically-reactive antineoplastic agents and peptides/proteins. The latter represent an emerging class of drugs which present significant analytical challenges. The use of o-phthalaldehyde analogues offering improved derivative stability and increased sensitivity will be described.
从生物基质中分析药物时，所能达到的灵敏度和选择性常常受到分析物物理化学性质的限制。大多数药物在生物系统中的固有反应性（即它们进行生物转化的倾向）进一步加剧了这些限制。为提高分析方法的质量而采用的一种非常有效的方法是在分析序列的某个阶段通过化学修饰（衍生化）改变药物的物理化学性质。这种方法已成功应用于各种情况，并提高了化学稳定性、分析选择性和灵敏度。在大多数情况下，从生物流体中进行药物分析都涉及一个色谱步骤；衍生化反应可以在色谱之前或之后进行。本文将介绍在临床药物分析中引入化学衍生化步骤所带来的优势（和局限性）的实例。具体而言，将重点关注化学反应性抗肿瘤药物以及肽/蛋白质的分析。后者代表了一类新兴药物，它们带来了重大的分析挑战。将描述使用具有更高衍生化稳定性和更高灵敏度的邻苯二甲醛类似物的情况。
