Abstract
Kinsenoside (KD), an active compound isolated from Anoectochilus roxburghii, has demonstrated multiple pharmacological activities including hepatoprotection, antihyperliposis, antihyperglycemia, and antiosteoporosis. To the best of our knowledge, there are no available data concerning its preclinical pharmacokinetics and bioavailability in beagle dogs. To support preclinical pharmacokinetic and bioavailability study, a reliable LC-MS/MS method was developed for KD concentration measurements in beagle dog plasma. The chromatographic separation was achieved on a Waters Atlantis® Hilic Silica column with an optimum mobile phase consisting of 5 mM ammonium acetate in water (pH 3.0 adjusted with acetic acid) and acetonitrile at a flow rate of 0.2 mL/min. Mass spectrometric analyses were carried out by monitoring multiple reaction monitoring transitions at m/z 265.2→102.9 for KD and m/z 174.0→128.0 for l-phenyl-d5-alanine-2,3,3-d3 (IS). The stability of KD in beagle dog whole blood and plasma was systematically evaluated. Lowering the temperature played a more critical role in stabilizing KD than decreasing the pH and adding esterase inhibitors, indicating that the major reason for instability of KD was probably due to chemical hydrolysis rather than esterase-mediated degradation. The currently developed method was validated and applied to a pharmacokinetic and bioavailability study of KD in beagle dogs following oral administration at a dose of 3 mg/kg. The absolute oral bioavailability for KD was determined to be 27.6%. Compared with typical glycosides, KD has a better bioavailability and is suitable for developing an oral dosage form.
Highlights
Kinsenoside (KD) is a major known active compound isolated from Anoectochilus roxburghii (Orchidaceae), a traditional herb used in many Asian countries for medicinal and culinary purposes [1]
Previous investigations showed that KD possessed hepatoprotective properties by decreasing the levels of the cytosolic enzymes such as lactate dehydrogenase (LDH), glutamic-oxalacetic transaminease (GOT), and glutamate pyruvic transaminease (GPT) [2,3]
The validated method was applied to a preclinical pharmacokinetic and bioavailability study of KD in beagle dogs following intravenous and oral administration
Summary
Kinsenoside (KD) is a major known active compound isolated from Anoectochilus roxburghii (Orchidaceae), a traditional herb used in many Asian countries for medicinal and culinary purposes [1]. Most of the previous analytical methods reported for the quantitation of KD utilized high-performance liquid chromatography with ultraviolet or evaporating light scattering detectors [3,4,8,9]. Due to their poor sensitivity, such methods are not suitable for in vivo pharmacokinetic research. The current work performed systemic stability assessment of KD in beagle dog whole blood and plasma and thereafter established blood sampling and treatment procedures to ensure a reliable concentration determination of the analyte. The developed and validated LC-MS/MS method was applied for pharmacokinetic and bioavailability study of KD in beagle dogs for the first time
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