Quantitative determination of bilobetin in rat plasma by HPLC–MS/MS and its application to a pharmacokinetic study

Abstract

Although bilobetin, a biflavone isolated from the leaves of Ginkgo biloba, represents a variety of pharmacological activities, to date there have been no validated determination methods for bilobetin in biological samples. Thus, we developed a liquid chromatographic method using a tandem mass spectrometry for the determination of bilobetin in rat plasma. After protein precipitation with acetonitrile including diclofenac (internal standard), the analytes were chromatographed on a reversed‐phased column with a mobile phase of purified water and acetonitrile (3:7, v/v, including 0.1% formic acid). The ion transitions of the precursor to the product ion were principally deprotonated ions [M − H]− at m/z 551.2 → 519.2 for bilobetin and 296.1 → 251.7 for the IS. The accuracy and precision of the assay were in accordance with US Food and Drug Administration regulations for the validation of bioanalytical methods. This analytical method was successfully applied to monitor plasma concentrations of bilobetin over time following intravenous administration in rats.

Pharmacokinetics of Shikimic Acid Following Intragastric and Intravenous Administrations in Rats

“…Deprotonated shikimic acid ([M-H] − at m / z 173.4) was fragmented into its largest product ion at m / z 136.6, with a collision energy of −16 eV. The transition from the IS precursor to the [M-H] − product ion occurred at 296.1→251.7 (collision energy −18 eV), as reported previously [ 20 , 21 , 22 ].…”

“…Although a synthetic method labeling shikimic acid with deuterium at positions C3 and C4 is available [ 23 ], it is impractical, as there are many steps and a low yield. Therefore, diclofenac served as a stable IS, as in many previous reports from our laboratory [ 20 , 21 , 22 ].…”

“…Instead, we tested solid-phase extraction using an anion exchange column, but the recovery rate was very low. We tested a simple precipitation procedure using a mixture of methanol and 10% ZnSO4 aqueous solution (4:1, v / v ) [ 18 ], trichloroacetic acid (5% w / v ) [ 19 ], methanol, and acetonitrile separately [ 20 , 21 , 22 ], but the sensitivity was poor. Therefore, the organic layer was evaporated after protein precipitation with five volumes of acetonitrile, and the plasma samples were finally concentrated twofold.…”

Homogenate-Ultrasound-Assisted Ionic Liquid Extraction of Total Flavonoids from Selaginella involven: Process Optimization, Composition Identification, and Antioxidant Activity

“…involven extract comprehensively, the UPLC-Q-TOF-MS method was employed, which could afford information pertaining to the targeted compounds, such as elemental composition, molecular structures, and molecular weight . So far, UPLC-Q-TOF-MS has been widely employed in the confirmation of bioactive components in natural products. − Therefore, the flavonoids in S. involven were identified by UPLC-Q-TOF-MS with the negative-ion mode.…”

Pretreatment and analysis techniques development of TKIs in biological samples for pharmacokinetic studies and therapeutic drug monitoring

“…Today, QqQ analyzers have become the most widely used analyzers for TKIs in LC-MS on account of the availability of robust mass spectrometers and their exceptional quantitative capacities [ 12 , [84] , [85] , [86] ]. In the cascade process of triple-quadrupole, specific precursor ions are selected in Q1, and product ions formed by CID are scanned with Q3 using multiple reaction monitoring (MRM) mode [ 26 , [87] , [88] , [89] ].…”