Gusev A I, Muddiman D C, Proctor A, Sharkey A G, Hercules D M, Tata P N, Venkataramanan R
Department of Chemistry, University of Pittsburgh, PA 15260, USA.
Rapid Commun Mass Spectrom. 1996;10(10):1215-8. doi: 10.1002/(SICI)1097-0231(19960731)10:10<1215::AID-RCM647>3.0.CO;2-K.
The identification and simultaneous quantification of Tacrolimus and its hepatic metabolites in baboons has been achieved using matrix-assisted laser desorption/ionization (MALDI) time-of-flight (TOF) mass spectrometry and static secondary-ion mass spectrometry (TOF-SIMS). Little fragmentation, high sensitivity and tolerance to contamination are the major advantages of these methods, allowing facile identification and quantification of metabolites produced in vitro with minor analyte isolation. Based on the MALDI and TOF-SIMS results, seven metabolites have been identified: de-methylated, di de-methylated, hydroxylated, di hydroxylated, de-methylated hydroxylated, dihydrodiol, and di de-methylated hydroxylated. The concentrations of the parent drug and its major metabolites (e.g. de-methylated, di de-methylated) were measured using Rapamycin as an internal standard. The time course of Tacrolimus and its major metabolites as a function of incubation time was calculated. Good correlation between SIMS and MALDI results was obtained.
利用基质辅助激光解吸/电离（MALDI）飞行时间（TOF）质谱和静态二次离子质谱（TOF-SIMS），已实现对狒狒体内他克莫司及其肝脏代谢物的鉴定和同时定量。这些方法的主要优点是碎片少、灵敏度高且耐污染，无需对分析物进行大量分离即可轻松鉴定和定量体外产生的代谢物。基于MALDI和TOF-SIMS结果，已鉴定出七种代谢物：去甲基化、双去甲基化、羟基化、双羟基化、去甲基化羟基化、二氢二醇和双去甲基化羟基化。以雷帕霉素作为内标物，测定了母体药物及其主要代谢物（如去甲基化、双去甲基化）的浓度。计算了他克莫司及其主要代谢物的时间进程与孵育时间的函数关系。SIMS和MALDI结果之间具有良好的相关性。
