LC–MS/MS Determination of the Absorption and Distribution Dynamics of the Bioactive Alkaloid Dendrobine Derived From Chinese <i>Dendrobium nobile</i>

Dendrobium nobile is a medicinal herb native to China with significant therapeutic properties. Its principal alkaloid derivative, Dendrobine (Den), has a variety of pharmacological activities, although its pharmacokinetics have not been fully elucidated. Here, we established and validated an LC-MS/MS technique and a rat model system to investigate the oral absorption and tissue distribution of Den. The assay demonstrated linearity over the 1-2000 ng/mL concentration range with correlation coefficients exceeding 0.99. Mean recovery values were 84.22%-106.15%, whereas relative standard deviations of matrix effects were 3.02%-10.53%. The precision values both within and between days were below 15%, with accuracies of 88.34% to 113.33%. Following intravenous administration of Den (5 mg/kg), plasma concentrations declined rapidly, yielding an average elimination half-life of 3.89 h. Oral administration at 40 mg/kg produced a similar rapid decline, with an average half-life of 3.72 h. Extensive first-pass metabolism contributed to the low (13%) oral bioavailability of this compound. Den distributed rapidly and broadly to tissues, with the highest accumulation in the liver, and was swiftly eliminated following intraperitoneal administration (40 mg/kg). This LC-MS/MS strategy provides a robust, sensitive, and reproducible platform for quantifying Den in biological matrices, supporting future pharmacokinetic and pharmacodynamic investigations.