Simultaneous determination by UPLC-MS/MS of seven bioactive compounds in rat plasma after oral administration of Ginkgo biloba tablets: application to a pharmacokinetic study

A rapid, reliable, and sensitive method was developed using ultra-performance liquid chromatography- tandem mass spectrometry （UPLC-MS/MS） with an electrospray ionization （ESI） source for determination of seven bioactive compounds in rat plasma after oral administration of Ginkgo biloba tablets （GBTs）. The method simultane- ously detects bilobalide （BB）, ginkgolide A （GA）, ginkgolide B （GB）, ginkgolide C （GC）, quercetin （QCT）, kaempferol （KMF）, and isorhamnetin （ISR） for pharmacokinetic study. The analytes and internal standard （IS） were extracted from rat plasma by acetidin. An MS/MS detection was conducted using multiple reaction monitoring （MRM） and operating in the negative ionization mode. The calibration curve ranges were 5-500, 5-500, 2.5-250, 1-100, 1-100, 1-100, and 1-100 ng/ml for BB, GA, GB, GC, QCT, KMF, and ISR, respectively. The mean recovery of the analytes ranged from 68.11% to 84.42%. The intra- and inter-day precisions were in the range of 2.33%-9.86% and the accuracies were between 87.67% and 108.37%. The method was used successfully in a pharmacokinetic study of GBTs. The phar- macokinetic parameters of seven compounds were analyzed using a non-compartment model. Plasma concentrations of the seven compounds were determined up to 48 h after administration, and their pharmacokinetic parameters were in agreement with previous studies.

Clinical Study on Treatment of Liver Fibrosis of Chronic Hepatitis B Patients with Ginkgo Leaf

Objective To study the anti-liver fibrosis effect of Ginkgo leaf in patients with chronic hepatitis B.Methods: Eighty-six patients with chronic hepatitis B were randomly divided into two groups with similar general condition. The 42 patients in the treated group were treated with Ginkgo leaf tablet (GLT), and the 44 patients in the control group were treated with Yiganling tablet. The treatment was conducted for 3 successive months in both groups. Changes in the histo-pathology of liver, serum levels of platelet activating factor (PAF), hyaluronic acid (HA), collagen type IV (C-IV), laminin (LN) and pro-collagen peptide type III (PC III) were observed before and after treatment. Results The markedly effective rate and the total effective rate in the treated group were 45.1% and 76.2% respectively, while in the control group the corresponding rates were 18. 2% and 43. 2%. Comparison between the two groups showed significant differenceP<0.01). Serum levels of PAF, HA, C-IV, LN and PC III were lowered significantly in the treated group after treatment. Compared with the corresponding parameters in the control group after treatment, the differences were all significant (P<0.01 orP<0.05). The pathological examination of liver showed improvement in both groups, the inflammation grade lowered in 10 patients (55. 6%) of the treated group and in 5 patients (35. 7%) of the control group, insignificant difference was shown between them. But in comparing the fibrosis staging lowering patients between the two groups, 12 patients (66. 7%) vs 3 patients (21.4%), the difference was significantP<0.05). Moreover, there were 4 patients in the control group with their fibrosis aggravated, while in the treated group, none was aggravatedP<0.05). Conclusion Ginkgo leaf tablet has some liver protective and anti-liver fibrosis benefits.