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

Abstract

In this study, a precise, rapid, and accurate ultra-performance liquid chromatography-tandem mass spectrometer (UPLC-MS/MS) method for the quantitation of O-demethyl nuciferine in mouse blood was developed, and pharmacokinetics of O-demethyl nuciferine was studied for the first time after sublingual injection and gavage. The study was performed with an UPLC ethylene bridged hybrid (UPLC BEH) (2.1 mm × 50 mm, 1.7 μm) column at 30°C, using diazepam as the internal standard (IS). The mobile phase consisted of acetonitrile-10 mmol/L ammonium acetate (containing 0.1% formic acid), with a flow rate of 0.4 mL/min for 4 min run time. Multiple reaction monitoring (MRM) modes of m/z 282.1→219.0 for O-demethyl nuciferine and m/z 296.2→265.1 for IS were utilized to conduct quantitative analysis. Protein in mouse blood was directly precipitated with acetonitrile for sample preparation. The linear range was 1-500 ng/mL with r > 0.995, and the lower limits of quantification (LLOQ) was 1 ng/mL. The intraand inter-day precision of O-demethyl nuciferine in mouse blood were RSD < 14% and RSD < 15%, respectively.r The accuracy ranged from 89.0% to 110.7%, with a recovery higher than 88.9%, while the matrix effect was between 103.1% and 108.7%. We further applied this UPLC-MS/MS method to the pharmacokinetic study on O-demethyl nuciferine after sublingual injection and gavage and determined the bioavailability to be 6.4%.

Simultaneous Determination of Ropivacaine and 3-Hydroxy Ropivacaine in Cerebrospinal Fluid by UPLC-MS/MS

“…The liquid chromatography conditions should be chosen in order to effectively separate endogenous interfering substances [ 27 – 29 ] from ropivacaine, 3-hydroxy ropivacaine, and internal standard. During the method development, a series of mobile phases were examined and compared: methanol or acetonitrile (containing 0.1% formic acid), 10 mmol/L ammonium acetate buffer solution (containing 0.1% formic acid) in acetonitrile or methanol, and 10 mmol/L ammonium acetate buffer solution (containing 0.05% ammonia) in methanol or acetonitrile.…”

Alkaloids from lotus (Nelumbo nucifera): recent advances in biosynthesis, pharmacokinetics, bioactivity, safety, and industrial applications

“…The lower bioavailability of liensinine was further confirmed by the research of Tong et al (2021). A pharmacokinetic study on O-demethyl nuciferine showed that its bioavailability was 6.4% following sublingual injection and gavage (Wu et al 2019). Generally, the poor solubility of alkaloids in lotus, including neferine, higenamine, nunciferine, and N-nunciferine leads to their relatively low in vivo bioavailability (Table 2), thereby limiting their further clinical application.…”