[Determination of vitexin in plasma by HPLC-MS/MS method and its pharmacokinetics in rats].

OBJECTIVE: To establish a HPLC-MS/MS method for the determination of vitexin in rat plasma and its pharmacokinetics. METHODS: The HPLC-MS/MS method used Capcell Pak C18 column (50 mm x 2.0 mm I. D., 5 microm). The mobile phase was methanol and water (95:5, V/V, containing 0.1% formic acid) at a flow rate of 0.2 mL/min. Electrospray ionization (ESI) in negative ion mode and multiple reaction monitoring (MRM) was used for the quantification of vitexin with a monitored transitions m/z 431-->311 for vitexin and m/z 269-->225 for internal standard (I. S., emodin). RESULTS: Linear calibration curves were obtained over the concentration range of 0.5-2000 ng/mL (r = 0.9960) with the lowest limit of quantification (LLOQ) of 0.5 ng/mL. The recovery was in the range of 76.1%-89.0%. The relative standard deviations for the intra-day and inter-day validation were less than 11%. CONCLUSION: The method is simple, accurate, fast, sensitive and suitable for the pharmacokinetic study of vitexin in rats.

[Effect of verapamil on pharmacokinetics of puerarin in rats].

OBJECTIVE: To investigate the effect of verapamil on the pharmacokinetics of puerarin in rats. METHOD: Puerarin with or without verapamil was administered intravenously or orally to rats. The concentration of puerarin in serum was determined by HPLC. RESULT: No significant difference was found between the control and 0.5 microg x g(-1) verapamil combined groups for intravenous administration, and there was significant difference between the control and 2. 5 microg x g(-1) verapamil combined groups (P < 0.05). When puerarin was administered orally with verapamil, significant difference was found between the control and combined groups (P < 0.05). CONCLUSION: Verapamil inhibited puerarin metabolism when puerarin was coadministered with verapamil, so it is necessary to change the therapeutic dose of puerarin.

[Preparation of self-microemulsifying soft capsule and investigation of dissolution for Duyiwei].

OBJECTIVE: To prepare the self-microemulsifying soft capsule (SMESC) of Duyiwei and investigate its dissolution property. METHODS: Through solubility experiment, self-microemulsification in vitro, drawing phase diagram and investigating the stability of solution, the optimum formulation was determined for Duyiwei. The dissolution of SMESC was measured, taking the commercial capsule as reference. RESULTS: In the optimum formulation, Labrasol, Transcutol P and ethyl oleate were screened as emulsifier, co-emulsifier and oil phase, respectively. The optimized proportion was 60: 25: 15. The dissolution of SMESC in water was more than 85% in 10 minutes, while that of the commercial capsule was less than 50% in 60 minutes. CONCLUSION: In comparison with the commercial capsule, the dissolution of SMESC is sufficiently improved in water.

[Assessment of Pueraria lobata isoflavone with self-microemulsifying drug delivery systems in vitro and in vivo].

OBJECTIVE: To evaluate the self-microemulsifying ability and dissolution behavior of pueraria lobata isoflavone in vitro and the pharmacokinetic behavior in rats. METHODS: The self-microemulsifying rate was evaluated by the self-microemulsifying time and the self-microemulsifying efficiency was evaluated by the particle size of resultant microemulsions. The plasma concentrations were evaluated by HPLC and dissolution and pharmacokinetic behavior of self-microemulsifying drug delivery systems were evaluated by comparison with commercial tablets. RESULTS: The system was self-microemulsified in 2 min and the particle size was less than 50 nm. The dis- solution of SMESC in distilled water was more than 90% at 10 min, while those of the commercial tablet were less than 50% at 120 min. 82% increase in the relative bioavailability was observed for the self microemulsifying drug delivery systems compared with Yufengningxin tablets. Tmax was smaller in the self-microemulsifying drug delivery systems compared with Yufengningxin tablets. CONCLUSION: The self-microemulsifying drug delivery systems can increase drug dissolution in vitro and absorption in vivo significantly.

Pharmacokinetic behaviors and oral bioavailability of oridonin in rat plasma.

AIM: To study the intravenous and oral pharmacokinetic behavior of oridonin and its extent of absolute oral bioavailability in rats. METHODS: Oridonin was administered to rats via iv (5, 10 and 15 mg/kg), po (20, 40 and 80 mg/kg) or ip administration (10 mg/kg). The concentrations of oridonin in rat plasma were determined by a high performance liquid chromatography with electrospray ionization mass spectrometric detection (HPLC/ESI-MS) method and the pharmacokinetic parameters were determined by non-compartmental analysis. RESULTS: The plasma concentration of oridonin after intravenous administration decreased polyexponentially, and the pharmacokinetic parameters of oridonin were dose-independent within the examined range. Oridonin was absorbed rapidly after oral gavage with a t(max) of less than 15 min; the extent of absolute bioavailability of oridonin following oral administration was 4.32%, 4.58% and 10.8%. The extent of absolute bioavailability of oridonin following intraperitoneal administration was 12.6%. CONCLUSION: First order rate pharmacokinetics were observed for oridonin within the range of iv doses, while the extent of absolute oral bioavailability was rather low and dose- dependent. The low and dose-dependent extent of oral bioavailability may be due to the saturation of first-pass effects.