Kamel Amin, Prakash Chandra
Pfizer Global Research and Development, Eastern Point Road, Groton, CT 06340, USA.
Curr Drug Metab. 2006 Dec;7(8):837-52. doi: 10.2174/138920006779010593.
Studies of the metabolic fate of drugs and other xenobiotics in living systems may be divided into three broad areas: (1) elucidation of biotransformation pathways through identification of circulatory and excretory metabolites (qualitative studies); (2) determination of pharmacokinetics of the parent drug and/or its primary metabolites (quantitative studies); and (3) identification of chemically-reactive metabolites, which play a key role as mediators of drug-induced toxicities (mechanistic studies). Mass spectrometry has been regarded as one of the most important analytical tools in studies of drug metabolism, pharmacokinetics and biochemical toxicology. With the commercial introduction of new ionization methods such as those based on atmospheric pressure ionization (API) techniques and the combination of liquid chromatography-mass spectrometry (LC-MS), it has now become a truly indispensable technique in pharmaceutical research. Triple stage quadrupole and ion trap mass spectrometers are presently used for this purpose, because of their sensitivity and selectivity. API-TOF mass spectrometry has also been very attractive due to its enhanced full-scan sensitivity, scan speed, improved resolution and ability to measure the accurate masses for protonated molecules and fragment ions. This review aims to survey the utility of mass spectrometry in drug metabolism and toxicology and to highlight novel applications and future trends in this field.
（1）通过鉴定循环和排泄代谢物来阐明生物转化途径（定性研究）；（2）测定母体药物和/或其主要代谢物的药代动力学（定量研究）；以及（3）鉴定作为药物诱导毒性介质起关键作用的化学反应性代谢物（机制研究）。质谱法一直被视为药物代谢、药代动力学和生化毒理学研究中最重要的分析工具之一。随着基于大气压电离（API）技术等新电离方法以及液相色谱 - 质谱联用（LC - MS）的商业化应用，它现已成为药物研究中真正不可或缺的技术。由于其灵敏度和选择性，目前三重四极杆和离子阱质谱仪用于此目的。API - TOF质谱仪因其增强的全扫描灵敏度、扫描速度、改进的分辨率以及测量质子化分子和碎片离子精确质量的能力也非常具有吸引力。本综述旨在探讨质谱法在药物代谢和毒理学中的应用，并突出该领域的新应用和未来趋势。
