Yamaguchi Hiroaki, Fujikawa Asuka, Ito Hajime, Tanaka Nobuaki, Furugen Ayako, Miyamori Kazuaki, Takahashi Natsuko, Ogura Jiro, Kobayashi Masaki, Yamada Takehiro, Mano Nariyasu, Iseki Ken
Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.
Biomed Chromatogr. 2013 Apr;27(4):539-44. doi: 10.1002/bmc.2826. Epub 2012 Sep 27.
A column-switching liquid chromatography/electrospray ionization tandem mass spectrometry to determine paclitaxel and its metabolites, 6α-hydroxypaclitaxel and p-3'-hydroxypaclitaxel, in human plasma was developed. The analytical system had a Shim-Pack MAYI-ODS (10 × 4.6 mm i.d.) trapping column with deproteinization ability that concentrates analytes and removes water-soluble components. This method covered a linearity range of 5-5000 ng/mL of concentrations in plasma for paclitaxel, a range of 0.87-870 ng/mL for 6α-hydroxypaclitaxel and a range of 0.87-435 ng/mL for p-3'-hydroxypaclitaxel. The intra-day precision and inter-day precision of analysis were less than 11.1%, and the accuracy was within ±14.4% at concentrations of 5, 50, 500 and 5000 ng/mL for paclitaxel, 0.87, 8.7, 87 and 870 ng/mL for 6α-hydroxypaclitaxel, and 0.87, 8.7, 87 and 435 ng/mL for p-3'-hydroxypaclitaxel. The total run time was 30 min. Our method was successfully applied to clinical pharmacokinetic investigation.
建立了一种柱切换液相色谱/电喷雾电离串联质谱法,用于测定人血浆中的紫杉醇及其代谢物6α-羟基紫杉醇和p-3'-羟基紫杉醇。该分析系统具有Shim-Pack MAYI-ODS(内径10×4.6 mm)捕集柱,具有去蛋白能力,可浓缩分析物并去除水溶性成分。该方法涵盖的血浆中紫杉醇浓度线性范围为5-5000 ng/mL,6α-羟基紫杉醇为0.87-870 ng/mL,p-3'-羟基紫杉醇为0.87-435 ng/mL。在紫杉醇浓度为5、50、500和5000 ng/mL、6α-羟基紫杉醇为0.87、8.7、87和870 ng/mL、p-3'-羟基紫杉醇为0.87、8.7、87和435 ng/mL时,日内精密度和日间精密度均小于11.1%,准确度在±14.4%以内。总运行时间为30分钟。我们的方法成功应用于临床药代动力学研究。