Wright Pat, Miao Zhuang, Shilliday Barclay
Pfizer Global Research and Development, Sandwich Laboratories, Kent, CT13 9NJ, UK.
Bioanalysis. 2009 Jul;1(4):831-45. doi: 10.4155/bio.09.63.
HPLC detector technology has advanced dramatically over the past 20 years, with a range of highly sensitive and specific detectors becoming available. What is still missing from the bioanalyst's armoury, however, is a highly sensitive detector that gives an equimolar response independent of the compound. This would allow for quantification of compounds without the requirement for a synthetic standard or a radiolabeled analogue. In particular, such a detector applied to metabolism studies would establish the relative significance of the various metabolic routes. The recently issued US FDA guidelines on metabolites in safety testing (MIST) focus on the relative quantitation of human metabolites being obtained as soon as feasible in the drug-development process. In this article, current detector technology is reviewed with respect to its potential for quantitation without authentic standards or a radiolabel and put in the context of the MIST guidelines. The potential for future developments are explored.
在过去20年里，高效液相色谱（HPLC）检测技术取得了巨大进步，一系列高灵敏度和高特异性的检测器应运而生。然而，生物分析人员的工具库中仍缺少一种高灵敏度的检测器，该检测器能给出与化合物无关的等摩尔响应。这将使得无需合成标准品或放射性标记类似物就能对化合物进行定量。特别是，这种应用于代谢研究的检测器将确定各种代谢途径的相对重要性。美国食品药品监督管理局（FDA）最近发布的关于安全性测试中代谢物（MIST）的指南侧重于在药物研发过程中尽快获得人体代谢物的相对定量。在本文中，我们将针对当前检测技术在无需真实标准品或放射性标记物的情况下进行定量的潜力进行综述，并结合MIST指南进行阐述。同时，还将探讨未来的发展潜力。
