Berna M, Shugert R, Mullen J
Department of Drug Disposition, Eli Lilly & Company, Lilly Corporate Center, Indianapolis, Indiana 46285, USA.
J Mass Spectrom. 1998 Feb;33(2):138-43. doi: 10.1002/(SICI)1096-9888(199802)33:2<138::AID-JMS617>3.0.CO;2-7.
A liquid chromatographic/mass spectrometric assay was developed for the determination of LY355703, a potent anti-tumor drug, in mouse and dog plasma. Empore (3M) C18 solid-phase extraction cartridges were used for sample preparation in conjunction with a positive pressure manifold. Chromatographic separation was obtained with a cyano high-performance liquid chromatographic column and detection was conducted using atmospheric pressure chemical ionization tandem mass spectrometry in the selected reaction monitoring mode. A structural analog, compound LY354504, was used as the internal standard. The assay was validated for the determination of LY355703 in mouse (ICR and NuNu) and dog (beagle) plasma. The lower and upper limits of quantitation were 2.1 and 527 ng ml-1, respectively, using a 0.1 ml plasma aliquot. The signal-to-noise ratio of a typical 2.1 ng ml-1 standard was approximately 40:1. The inter-day precision (relative standard deviation) and accuracy (relative error) derived from the analysis of validation samples at five concentrations ranged from 2.7 to 7.6% and from 4.8 to 4.5%, respectively. Throughput is approximately one sample every 3 min. This assay is simple, sensitive, accurate, precise and is being used to support toxicokinetic studies in dog and mouse.
开发了一种液相色谱/质谱分析法，用于测定小鼠和犬血浆中的强效抗肿瘤药物LY355703。使用Empore（3M）C18固相萃取柱结合正压歧管进行样品制备。采用氰基高效液相色谱柱进行色谱分离，并在选择反应监测模式下使用大气压化学电离串联质谱进行检测。使用结构类似物化合物LY354504作为内标。该分析方法经过验证，可用于测定小鼠（ICR和NuNu）和犬（比格犬）血浆中的LY355703。使用0.1 ml血浆等分试样时，定量下限和上限分别为2.1和527 ng ml-1。典型的2.1 ng ml-1标准品的信噪比约为40:1。对五个浓度的验证样品进行分析得出的日间精密度（相对标准偏差）和准确度（相对误差）分别为2.7%至7.6%和4.8%至4.5%。通量约为每3分钟一个样品。该分析方法简单、灵敏、准确、精密，正用于支持犬和小鼠的毒代动力学研究。
