Lappin Graham, Wagner Claudia C, Langer Oliver, van de Merbel Nico
Xceleron Inc., Germantown, MD, USA.
Bioanalysis. 2009 May;1(2):357-66. doi: 10.4155/bio.09.40.
In a microdosing study, subpharmacologically active doses of drug are given to human volunteers at an early stage of development in order to obtain preliminary pharmacokinetic data. The very low doses of drug administered (≤100 µg) consequently lead to very low concentrations of drug appearing in the body and therefore highly sensitive analytical techniques are required. There are three such analytical technologies currently used in microdosing studies: PET, liquid chromatography (LC)-tandem mass spectrometry (MS/MS) and accelerator mass spectrometry (AMS). Both PET and AMS employ radioisotopic tracers. PET is an imaging technique and AMS is an extremely sensitive isotope ratio method, able to measure drug concentrations in the ag/ml range. LC-MS/MS does not require the presence of an isotopic tracer and its sensitivity is in the pg/ml range. This review examines each of these three analytical modalities in the context of performing microdosing studies.
在微剂量研究中，在药物研发的早期阶段，会给人类志愿者服用低于药理活性剂量的药物，以获取初步的药代动力学数据。所给予的药物剂量极低（≤100微克），因此导致体内出现的药物浓度非常低，所以需要高度灵敏的分析技术。目前在微剂量研究中使用的此类分析技术有三种：正电子发射断层扫描（PET）、液相色谱（LC）-串联质谱（MS/MS）和加速器质谱（AMS）。PET和AMS都使用放射性同位素示踪剂。PET是一种成像技术，AMS是一种极其灵敏的同位素比率方法，能够测量纳克/毫升范围内的药物浓度。LC-MS/MS不需要有同位素示踪剂，其灵敏度在皮克/毫升范围内。本综述在进行微剂量研究的背景下审视这三种分析方式中的每一种。
