Xia Yuan-Qing, Miller Jeffrey D, Bakhtiar Ray, Franklin Ronald B, Liu David Q
Department of Drug Metabolism, Merck Research Laboratories, Rahway, NJ 07065, USA.
Rapid Commun Mass Spectrom. 2003;17(11):1137-45. doi: 10.1002/rcm.1037.
A new type of quadrupole linear ion trap mass spectrometer, Q TRAP trade mark LC/MS/MS system (Q TRAP trade mark ), was evaluated for its performance in two studies: firstly, the in vitro metabolism of gemfibrozil in human liver microsomes, and, secondly, the quantification of propranolol in rat plasma. With the built-in information-dependent-acquisition (IDA) software, the instrument utilizes full scan MS in the ion trap mode and/or constant neutral loss scans as survey scans to trigger product ion scan (MS(2)) and MS(3) experiments to obtain structural information of drug metabolites 'on-the-fly'. Using this approach, five metabolites of gemfibrozil were detected in a single injection. This instrument combines some of the unique features of a triple quadrupole mass spectrometer, such as constant neutral loss scan, precursor ion scan and multiple reaction monitoring (MRM), together with the capability of a three-dimensional ion trap. Therefore, it becomes a powerful instrument for metabolite identification. The fast duty cycle in the ion trap mode allows the use of full product ion scan for quantification. For the quantification of propranolol, both MRM mode and full product ion scan in the ion trap mode were employed. Similar sensitivity, reproducibility and linearity values were established using these two approaches. The use of the product ion scan mode for quantification provided a convenient tool in selecting transitions for improving selectivity during the method development stage.
在两项研究中对一种新型四极杆线性离子阱质谱仪（Q TRAP商标LC/MS/MS系统，即Q TRAP）的性能进行了评估：其一，吉非贝齐在人肝微粒体中的体外代谢；其二，大鼠血浆中普萘洛尔的定量分析。借助内置的信息依赖采集（IDA）软件，该仪器在离子阱模式下利用全扫描质谱和/或恒定中性丢失扫描作为普查扫描，以触发产物离子扫描（MS(2)）和MS(3)实验，从而“即时”获取药物代谢物的结构信息。采用这种方法，单次进样即可检测到吉非贝齐的5种代谢物。该仪器结合了三重四极杆质谱仪的一些独特功能，如恒定中性丢失扫描、前体离子扫描和多反应监测（MRM），以及三维离子阱的功能。因此，它成为代谢物鉴定的强大工具。离子阱模式下的快速工作周期允许使用全产物离子扫描进行定量分析。对于普萘洛尔的定量分析，采用了MRM模式和离子阱模式下的全产物离子扫描。使用这两种方法获得了相似的灵敏度、重现性和线性值。在方法开发阶段，使用产物离子扫描模式进行定量分析为选择跃迁以提高选择性提供了便利工具。
