College of Pharmacy, Kyung Hee University, Seoul 130-701, South Korea.
J Chromatogr B Analyt Technol Biomed Life Sci. 2012 Jul 1;900:1-10. doi: 10.1016/j.jchromb.2012.05.011. Epub 2012 May 17.
Gas chromatography-mass spectrometry (GC/MS) and liquid chromatography-mass spectrometry (LC/MS) were compared for their capacity to metabolite identification, sensitivity, and speed of analysis for propofol and its metabolites in urine samples. Acidic hydrolysis, liquid-liquid extraction (LLE), and trimethylsilyl (TMS) derivatization procedures were applied for GC/MS analysis. The LC/MS analysis used a simple sample pretreatment based on centrifugation and dilution. Propofol and four metabolites were successfully analyzed by GC/MS following TMS derivatization. One compound, di-isopropanolphenol was tentatively characterized as a new metabolite observed for the first time in human urine. The TMS derivatization greatly improved the chromatographic properties and detection sensitivity, especially for hydroxylated metabolites. The lower limits of quantitation (LLOQ) of propofol were about 325 and 0.51 ng/mL for the GC/MS scan mode and selected ion monitoring (SIM) mode, respectively. In addition, five conjugated propofol metabolites were successfully analyzed by LC-MS/MS in negative ion mode. The detection sensitivity for these conjugated metabolites could be greatly enhanced by the addition of triethylamine to the mobile phase without any loss of LC resolution capacity. The LLOQs of propofol-glucuronide (PG) were about 1.17 and 2.01 ng/mL for the LC-MS-selected ion monitoring (SIM) and multiple reaction monitoring (MRM) mode, respectively. Both GC/MS and LC/MS methods sensitively detected nine metabolites of propofol and could be used to provide complementary data for the reasonable propofol metabolism study. Urinary excretion profiles for propofol and its metabolites following administration to human were suggested based on the total ion chromatograms obtained by GC/MS and LC/MS methods, respectively.
气相色谱-质谱联用（GC/MS）和液相色谱-质谱联用（LC/MS）在鉴定代谢物的能力、灵敏度和分析速度方面进行了比较，用于检测尿液样本中的丙泊酚及其代谢物。采用酸水解、液-液萃取（LLE）和三甲基硅烷（TMS）衍生化程序进行 GC/MS 分析。LC/MS 分析采用基于离心和稀释的简单样品预处理。丙泊酚和四种代谢物经 TMS 衍生化后，成功地通过 GC/MS 进行了分析。一种化合物，二异丙醇苯酚，被初步鉴定为一种新的代谢物，这是首次在人尿中观察到。TMS 衍生化极大地改善了色谱性质和检测灵敏度，特别是对羟基化代谢物。丙泊酚的定量下限（LLOQ）分别约为 325 和 0.51 ng/mL，用于 GC/MS 扫描模式和选择离子监测（SIM）模式。此外，五种共轭丙泊酚代谢物通过 LC-MS/MS 在负离子模式下成功地进行了分析。通过在流动相中添加三乙胺，可以大大提高这些共轭代谢物的检测灵敏度，而不会损失 LC 分辨率能力。丙泊酚-葡萄糖醛酸苷（PG）的LLOQ 分别约为 1.17 和 2.01 ng/mL，用于 LC-MS-SIM 和多反应监测（MRM）模式。GC/MS 和 LC/MS 方法均能灵敏地检测丙泊酚的九种代谢物，可用于提供合理的丙泊酚代谢研究的补充数据。基于通过 GC/MS 和 LC/MS 方法分别获得的总离子色谱图，提出了丙泊酚及其代谢物在人体中的尿排泄谱。
