Pharmacokinetic and ocular microdialysis study of oral ginkgo biloba extract in rabbits by UPLC-MS/MS determination

Abstract

Objectives The purpose of this work was to determine and investigate the absorption of ginkgo terpenoids (GT) in plasma and aqueous humour after oral administration of ginkgo biloba extract (GBE) by UPLC‐MS/MS method. Methods The UPLC‐MS/MS determination of GT employed the multiple reaction monitoring mode using an electrospray negative ionization. The rabbits were orally administered the suspension of GBE at a dose of 500 mg/kg. Serial plasma and dialysate samples were collected at the corresponding time and then analysed by UPLC‐MS/MS. Key findings In plasma, the mean AUC from 0 to 48 h was 14.12, 12.59, 23.75, 1.51 h μg/ml for GLJ and 5.34 h μg/ml for GLA, GLB, GLC, GLJ and BLL, respectively. In aqueous humour, the five ginkgo terpenoids have been detected. Compared with the other four GT, BLL has better absorption in the eyes. Conclusions A selective and reproducible UPLC‐MS/MS method was developed and validated to determine and investigate the absorption of ginkgo terpenoids in plasma and aqueous humour of rabbits after oral administration of GBE. The main five ginkgo terpenoids could be absorbed into eyes.

Development and evaluation of Panax notoginseng saponins contained in an in situ pH-triggered gelling system for sustained ocular posterior segment drug delivery

“…Before the experiments, the animals were kept in an environmentally controlled feeding room for 7 d. The ocular bioavailability of PNS in the vitreous of rabbit eyes was determined by microdialysis [38] . Linear microdialysis probes (Bioanalytical Systems, Inc. West Lafayette, IN, USA; 30 kDa MWCO; 320 μm outer diameter) were carefully implanted into the vitreous of right eyes of 12 rabbits (divided into two groups), which were anesthetized with a subcutaneous injection of lidocaine hydrochloride (about 0.75 mL/kg, judged by the absence of response of the eye to external stimuli).…”

“…An in vivo microdialysis recovery experiment was conducted [38] . In a microdialysis experiment, there are usually two types of recoveries: in vitro recovery and in vivo recovery.…”

“…Further details were provided in the supplementary material, http://links.lww.com/AHM/A5. The linear equation was drawn from (C d -C p ) versus C p (C d , drug concentration in dialysate; C p , drug concentration in the infusion fluid), and the recovery was given by the slope of the line [38] . The zero-abscissa assumed that the corresponding concentration around the probe compound in the solution was consistent with the actual concentration.…”

Determination and pharmacokinetics and bioavailability of O-demethyl nuciferine in mice by UPLC–MS/MS

“…Compared with liquid chromatography-tandem mass spectrometer (LC-MS/MS), ultra-performance LC-MS/MS (UPLC-MS/MS) has higher detection sensitivity with more powerful separation and analytical capability, which are essential for studying Chinese medicine with complex contents and the in vivo metabolism in such compound systems [12][13][14]. Herein, by taking advantage of the powerful UPLC-MS/MS, for the first time, we developed a precise, rapid, and accurate method for the determination of O-demethyl nuciferine in mouse blood using UPLC-MS/MS, and we further studied the pharmacokinetics and bioavailability after sublingual injection and gavage using the newly developed UPLC-MS/MS.…”

Cytotoxic and genotoxic potential of Ginkgo biloba L., in industrialized and without-additive forms

“…It is popularly known as ginkgo or maidenhair tree, and has high concentrations of ginkgolide diterpenes, bilobalide sesquiterpenes, triterpenes, polyphenols, ginkgolide acids, flavones, flavonols and biflavonoids in the foliage (POLANSKI et al, 2016). This plant is worldwide marketed in herbal stores and drugstores, in dehydrated form and in tablets and/or capsules, respectively (MAHMOUDIAN-SANI et al, 2017;WANG et al, 2017). Tea of fresh ginkgo leaves was evaluated for its toxic potential at the cellular level, and it was verified that this plant was neither cytotoxic nor genotoxic to the bioassays used.…”