Determination of myrislignan levels in BALB/c mouse plasma by LC-MS/MS and a comparison of its pharmacokinetics after oral and intraperitoneal administration

Abstract

Background Myrislignan is a natural product from Myristica sp. with diverse pharmacological activities. Recently, the anti-Toxoplasma gondii (T. gondii) activity of myrislignan has been proposed, and in vivo studies of its pharmacokinetics in BALB/c mice are necessary to further evaluate the clinical effects of myrislignan. Results In this study, a sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated to quantify myrislignan levels in mouse plasma using dehydrodiisoeugenol as an internal standard (IS) in positive ion mode. Chromatographic separation of the analytes was achieved using an ACE Ultracore Super C18 analytical column (2.5 μm, 2.1 × 50 mm) at 30 °C. A gradient mobile phase consisting of water (0.1 % formic acid) and acetonitrile (0.1 % formic acid) was delivered at a flow rate of 0.4 mL/min. Myrislignan and the IS eluted at 1.42 and 1.71 min, respectively. A good excellent linear response across the concentration range of 1-1000 ng/mL was achieved (r2 = 0.9973). The lower limit of quantification (LLOQ) was 1 ng/mL, and the inter- and intra-day accuracy and precision of the method showed relative standard deviations (RSDs) less than 10 %. The method was applied to examine the pharmacokinetics of myrislignan in mouse plasma following a single oral administration of 200 mg/kg or intraperitoneal administration of 50 mg/kg myrislignan, and the bioavailability (F) of orally administered myrislignan was only 1.97 % of the bioavailability of intraperitoneally administered myrislignan. Conclusions A rapid and sensitive LC-MS/MS method has been was developed, validated and successfully used to determine myrislignan levels in mice after oral or intraperitoneal administration. This study is the first to report the pharmacokinetic parameters of myrislignan in mice and to compare its pharmacokinetics after oral and intraperitoneal administration, which will be useful for further research on the administration of myrislignan in animals and humans.

NF-κB Inhibitor Myrislignan Induces Ferroptosis of Glioblastoma Cells via Regulating Epithelial-Mesenchymal Transformation in a Slug-Dependent Manner

“…Myrislignan is a lignan isolated from Myristica fragrans Houtt with diverse pharmacological activities [ 13 ]. It can be metabolized by liver CYP450 enzymes and penetrate the blood-brain barrier through passive diffusion [ 16 , 17 ].…”

“…Therefore, there is need to identify potential target genes and develop effective targeted drugs to improve the outcomes of glioma patients. Myrislignan is a lignan isolated from Myristica fragrans Houtt with diverse pharmacological activities [13]. It can be metabolized by liver CYP450 enzymes and penetrate the blood-brain barrier through passive diffusion [16,17].…”

“…In this research, we revealed an antitumor activity of myrislignan, a lignan isolated from Myristica fragrans Houtt [ 13 ], which was reported to affect the activity of NF- κ B signaling pathway and showed the capability of anti-inflammatory [ 14 ]. We investigated the inhibitory activity of myrislignan against GBM in vivo and in vitro .…”

Myrislignan Targets Extracellular Signal-regulated Kinase (ERK) and Modulates Mitochondrial Function to Dampen Osteoclastogenesis and Ovariectomy-i nduced Osteoporosis

“…They have the advantage of availability, low manufacturing cost, and lack of adverse effects, which has been an essential source of developing new medicine gradually (22,38). In searching for a new bioactive natural treatment with anti-osteoclast formation, we found that MRL functioned as anti-in ammation, anti-cancer, and anti-mitochondria (32,33,47). However, MRL's speci c mechanisms of action in osteoclast formation and mitochondrial function have yet to be investigated deeply.…”

Determination and pharmacokinetics study of UK-5099 in mouse plasma by LC–MS/MS

“…The stability was evaluated by analyzing repeats ( n = 6) of QC samples with concentrations of 15 ng·mL −1 , 400 ng·mL −1 and 4000 ng·mL −1 under different sample storage and processing procedures: (1) plasma samples were kept at ambient temperature for 24 h (2) plasma samples were stored at -20 °C for 60 days (3) plasma samples were stored in an autosampler at 4 °C for 24 h (4) plasma samples were measured after three freeze–thaw cycles (25 °C to -20 °C) [ 19 ].…”