Study of the effect of Wuzhi tablet (Schisandra sphenanthera extract) on tacrolimus tissue distribution in rat by liquid chromatography tandem mass spectrometry method.
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.
Qin
Xiao-ling
XL
Institute of Clinical Pharmacology, School of Pharmaceutical Sciences, Sun Yat-sen University, 74 Zhongshan Road II, Guangzhou, China.
Bi
Hui-chang
HC
Wang
Chang-xi
CX
Li
Jia-li
JL
Wang
Xue-ding
XD
Liu
Long-shan
LS
Chen
Xiao
X
Huang
Min
M
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
D010936:Plant Extracts; C058028:immunomycin; D016559:Tacrolimus