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 C₁₈ 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. Copyright © 2009 John Wiley & Sons, Ltd.