title: Study of the effect of Wuzhi tablet (Schisandra sphenanthera extract) on tacrolimus tissue distribution in rat by liquid chromatography tandem mass spectrometry method.
abstract: A liquid chromatography/tandem mass spectrometry (LC-MS/MS) method was developed and validated for determining tacrolimus (FK506) in rat tissues to study the effect of Schisandra sphenanthera extract on FK506 tissue distribution. After a liquid-liquid extraction with ethyl acetate, FK506 and ascomycin (IS) were subjected to LC-MS/MS analysis using positive electrospray ionization under multiple reactions monitoring mode. Chromatographic separation of FK506 and ascomycin was achieved on a Hypersil BDS C(18) column with a mobile phase consisting of methanol-water (containing 2 mM ammonium acetate, 95 : 5, v/v). The intra- and inter-batch precision of the method were less than 8.8 and 9.8%, respectively. The intra- and inter-batch accuracies ranged from 97.5 to 104.0%. The lowest limit of quantification for FK506 was 0.5 ng/mL. The method was applied to a FK506 tissue distribution study with or without a dose of Wuzhi (WZ) tablet. Most of the FK506 tissue concentrations were slightly increased after a concomitant WZ tablet dose, but the whole blood concentration of FK506 was dramatically increased 3-fold after a concomitant WZ tablet dose. These results indicated that the LC-MS/MS method was rapid and sensitive enough to quantify FK506 in different rat tissues, and strict drug monitoring is recommended when co-administering WZ tablet in clinical use.
authors.affiliation: Institute of Clinical Pharmacology, School of Pharmaceutical Sciences, Sun Yat-sen University, 74 Zhongshan Road II, Guangzhou, China.
authors.forename: Xiao-ling
authors.initials: XL
authors.lastname: Qin
authors.forename: Hui-chang
authors.initials: HC
authors.lastname: Bi
authors.forename: Chang-xi
authors.initials: CX
authors.lastname: Wang
authors.forename: Jia-li
authors.initials: JL
authors.lastname: Li
authors.forename: Xue-ding
authors.initials: XD
authors.lastname: Wang
authors.forename: Long-shan
authors.initials: LS
authors.lastname: Liu
authors.forename: Xiao
authors.initials: X
authors.lastname: Chen
authors.forename: Min
authors.initials: M
authors.lastname: Huang
mesh_terms: D000818:Animals; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004347:Drug Interactions; D016014:Linear Models; D008297:Male; D010936:Plant Extracts / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D032141:Schisandra / Q000737:chemistry*; D012680:Sensitivity and Specificity; D016559:Tacrolimus / Q000031:analogs & derivatives / Q000032:analysis / Q000737:chemistry / Q000493:pharmacokinetics*; D053719:Tandem Mass Spectrometry / Q000379:methods*; D014018:Tissue Distribution
chemical_list: D010936:Plant Extracts; C058028:immunomycin; D016559:Tacrolimus