Pharmacokinetic comparisons of five different combinations of Zhi-zi-chi Decoction among rats: Competing mechanisms between geniposide and genistein>

Abstract

Zhi-zi-chi decoction (ZZCD), a well-known traditional Chinese medicine prescription, is a combination of Gardenia jasminoides fruit (GJF) and fermented soybean (FS). ZZCD has been used for treating depression, insomnia, and other diseases in China for thousands of years. A rapid, accurate, and sensitive ultra-high-performance liquid chromatography–tandem mass spectrometry (UPLC–MS/MS) method was developed for the simultaneous determination of the plasma concentrations of two representative ingredients, namely, geniposide and genistein. Adult Wistar rats were orally administered with ZZCD1 (GJF:FS, 1:1 (w/w), equals to 45.22 mg/kg of geniposide and 1.11 μ g/kg of genistein), ZZCD2 (GJF:FS, 1:2 (w/w), equals to 33.31 mg/kg of geniposide and 1.10 μ g/kg of genistein), ZZCD3 (GJF:FS, 1:4 (w/w), equals to 25.91 mg/kg of geniposide and 1.06 μ g/kg of genistein), ZZCD4 (GJF:FS, 2:1 (w/w), equals to 62.45 mg/kg of geniposide and 0.368 μ g/kg of genistein), and ZZCD5 (GJF:FS, 10:1 (w/w), equals to 77.73 mg/kg of geniposide and 0.54 μ g/kg of genistein). The analytes were quantified using the multiple reaction monitoring mode with the electrospray ion source in positive (genistein) and negative (geniposide and IS) electrospray ionization. All calibration curves exhibited good linearity ( R 2 > 0.9992) over the measured ranges. The intra- and inter-day precisions were within 12.32%, and the accuracy ranged from 96.37% to 120.43%. The extraction recovery and matrix effect yielded satisfactory results. The method was successfully applied in a pharmacokinetic study of geniposide and genistein in rat plasma after the oral administration of five different combinations of ZZCDs.