Development of a sensitive LC–MS/MS method for the determination of bilobalide in rat plasma with special consideration of ex vivo bilobalide stability: Application to a preclinical pharmacokinetic study

Wang, Jie; Ouyang, Jingping; Liu, You‐Ping; Jia, Xian; You, Song; He, Xin; Di, Xin

doi:10.1016/j.jpba.2014.03.003

Cited by 10 publications

(9 citation statements)

References 31 publications

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“…To date, these decomposition byproducts have not been characterized and the pathway for irreversible BB decomposition remains unknown. This information is important for both isolation and pharmacokinetics: BB degrades in rat heparinized plasma ( k = 0.5465 h –1 ) and even in pH 7.4 buffer ( k = 0.1868 h –1 ) …”

Section: Results and Discussionmentioning

confidence: 99%

Synthetic, Mechanistic, and Biological Interrogation of Ginkgo biloba Chemical Space En Route to (−)-Bilobalide

et al. 2020

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Here we interrogate the structurally dense (1.63 mcbits/Å 3 ) GABA A receptor antagonist bilobalide, intermediates en route to its synthesis and related mechanistic questions. 13 C isotope labeling identifies an unexpected bromine migration en route to an α-selective, catalytic asymmetric Reformatsky reaction, ruling out an asymmetric allylation pathway. Experiment and computation converge on the driving forces behind two surprising observations. First, an oxetane acetal persists in concentrated mineral acid (1.5 M DCl in THF-d 8 /D 2 O); its longevity is correlated to destabilizing steric clash between substituents upon ring-opening. Second, a regioselective oxidation of des-hydroxybilobalide is found to rely on lactone acidification through lone-pair delocalization, which leads to extremely rapid intermolecular enolate equilibration. We also establish equivalent effects of (−)-bilobalide and the nonconvulsive sesquiterpene (−)-jiadifenolide on action potential-independent inhibitory currents at GABAergic synapses, using (+)-bilobalide as a negative control. The high information density of bilobalide distinguishes it from other scaffolds, and may characterize natural product (NP) space more generally. Therefore, we also include a Python script to quickly (ca. 132,000 molecules/minute) calculate information content (Böttcher scores), which may prove helpful to identify important features of NP space.

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Section: Results and Discussionmentioning

confidence: 99%

Synthetic, Mechanistic, and Biological Interrogation of Ginkgo biloba Chemical Space En Route to (−)-Bilobalide

et al. 2020

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“…To solve this problem, it is urgent to develop effective methods to analyze and stabilize the BB content in biological samples in vitro. Wang, Ouyang, et al (2014) found that ethylene diamine tetraacetic acid (EDTA)was efficient for BB stabilization, although it could not completely circumvent degradation of BB in rat plasma at 37 C. Improved efficiency of EDTA was It is speculated that PON may be mainly involved in the hydrolysis of double bromine amine in rat plasma. Since most experiments are carried out at room temperature, researchers tried to acidify rat plasma containing EDTA to prevent BB degradation at room temperature.…”

Section: Pharmacokinetics Of Bbmentioning

confidence: 99%

“…To solve this problem, it is urgent to develop effective methods to analyze and stabilize the BB content in biological samples in vitro. Wang, Ouyang, et al (2014) found that ethylene diamine tetraacetic acid (EDTA)was efficient for BB stabilization, although it could not completely circumvent degradation of BB in rat plasma at 37°C. Improved efficiency of EDTA was found at room temperature (25°C) and complete inhibition of BB degradation by EDTA was achieved at 4°C for at least 10 hr.…”

Section: Pharmacokinetics Of Bbmentioning

confidence: 99%

“…After gastric administration of BB at a dose of 28 mg/kg, the T max was 18–38 min, the C max was about 4,653–6,853 ng/ml and the T 1/2 was 31.2–43.8 min. These data showed that the pharmacokinetics of BB was linear in the range of 7–28 mg/kg, indicating the pharmacokinetic behavior of BB was dose‐dependent (Dou et al, 2017; Wang et al, 2014). In addition, studies have reported the effects of food and gender on the pharmacokinetics of BB.…”

Section: Pharmacokinetics Of Bbmentioning

confidence: 99%

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Bilobalide: A review of its pharmacology, pharmacokinetics, toxicity, and safety

Xie

et al. 2021

Phytotherapy Research

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Bilobalide is a natural sesquiterpene trilactone from Ginkgo biloba leaves. It has good water solubility and is widely used in food and pharmaceutical fields. In the last decade, a plethora of studies on the pharmacological activities of bilobalide has been conducted and demonstrated that bilobalide possessed an extensive range of pharmacological activities such as neuroprotective, antioxidative, antiinflammatory, antiischemic, and cardiovascular protective activities. Pharmacokinetic studies indicated that bilobalide may have the characteristics of rapid absorption, good bioavailability, wide distribution, and slow elimination. This review aims to summarize the advances in pharmacological, pharmacokinetics, toxicity, and safety studies of bilobalide in the last decade with an emphasis on its neuroprotective and antiinflammatory activities, to provide researchers with the latest information and point out the limitations of relevant research at the current stage and the aspects that should be strengthened in future research.

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“…An aliquot of 10 L internal standard solution (500 ng/mL) and 20 L HCl (2.5 mol/L) were added into a 200 L biological sample [25]. The mixture was extracted with 1.4 mL ethyl acetate by vortex-mixing for 5 min.…”

Section: Sample Preparationmentioning

confidence: 99%

Pharmacokinetic studies of ginkgolide K in rat plasma and tissues after intravenous administration using ultra-high performance liquid chromatography-tandem mass spectrometry

Fan

Liu

Guo

et al. 2015

Journal of Chromatography B

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Ginkgolide K (GK), a derivative compound of ginkgolide B, has been recently isolated from the leaves of Ginkgo biloba. It is a powerful natural platelet activate factor (PAF) antagonist, and also has obvious protect effects for cerebral ischemia. However, no reports have been described for the pharmacokinetic study of GK. In this study, a simple, sensitive and reliable ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method has been developed for the determination of GK in rat plasma and tissues. Biological samples were pretreated by an efficient liquid-liquid extraction with ethyl acetate. The chromatographic separation was achieved on an Agilent ZORBAX SB-Aq column (4.6 mm × 50 mm, 1.8 μm) with a mobile phase of 0.5% aqueous formic acid (A)-menthol (B). Quantitation was carried out on a triple quadruple mass spectrometry using positive electrospray ionization in multiple reaction monitoring mode. Diazepam was used as internal standard (IS). The ion transitions monitored were set at m/z 407.10 → 389.20 and m/z 285.08 → 193.10 for GK and IS, respectively. The developed method was fully validated and successfully applied to the pharmacokinetics and tissue distribution study of GK after intravenous administration. The current results have indicated that pharmacokinetic parameters of GK vary in a dose-dependent manner with rapid elimination in 4h. The major distribution tissues of GK in rats were liver and kidney. This study would provide critical information to promote the future study of GK.

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Development of a sensitive LC–MS/MS method for the determination of bilobalide in rat plasma with special consideration of ex vivo bilobalide stability: Application to a preclinical pharmacokinetic study

Cited by 10 publications

References 31 publications

Synthetic, Mechanistic, and Biological Interrogation of Ginkgo biloba Chemical Space En Route to (−)-Bilobalide

Synthetic, Mechanistic, and Biological Interrogation of Ginkgo biloba Chemical Space En Route to (−)-Bilobalide

Bilobalide: A review of its pharmacology, pharmacokinetics, toxicity, and safety

Pharmacokinetic studies of ginkgolide K in rat plasma and tissues after intravenous administration using ultra-high performance liquid chromatography-tandem mass spectrometry

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