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Pharmacokinetic study of hypaphorine, a potential agent for treating osteoclast-based bone loss, on rats using LC-MS/MS

Author(s):

Taiyuan Zhang*, Yan Yan, Yutao Xue, Shan Xiong*, Wenwen Ran and Qiao Xu  

Abstract:


Aim and Objective: A high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the determination of hypaphorine, a potential agent for treating osteoclast-based bone loss, was developed and valadated in rat plasma.

Materials and Methods: Plasma samples were pretreated by the protein precipitation. Chromatographic separation was performed using an Inertsil ODS-3 column (50 mm × 4.6 mm, 5 μm). The mobile phase consisted of water (containing 0.1% formic acid) and acetonitrile in a gradient mode at a flow rate of 0.5 mL/min. The acquisition was carried out in selected reaction monitoring (SRM) of the transitions from protonated precursor ion [M + H]+ to the particular daughter ion and the mass transitions of hypaphorine and IS were 247 → 188 and m/z 219 → 188, respectively. The method was validated in terms of selectivity, linearity, accuracy and precision, extraction recovery and matrix effect, stability and carryover.

Results: It showed good linearity over the range of 1-2000 ng/mL (R2 = 0.9978). The intra-batch accuracy was within 93.95-105.81% and the precision was within 4.92-11.53%. The inter-batch accuracy was within 96.18-100.39% with a precision of 6.22-11.23%. The extraction recovery and matrix factors were acceptable.

Conclusion: The simple and rapid method was successfully applied to the pharmacokinetics study in rats following oral administration of hypaphorine at the doses of 0.5, 1.5, and 4.5 mg/kg.

Keywords:

osteoclasts, hypaphorine, abrine, LC-MS/MS, pharmacokinetics, rats

Affiliation:

Department of Traumatic Orthopaedics, Affiliated Jinan Third Hospital of Jining Medical University, Jinan, 250132, Department of Paediatrics, Affiliated Jinan Third Hospital of Jining Medical University, Jinan, 250132, Institute of Materia Medica, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, 250117, Institute of Materia Medica, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, 250117, Institute of Materia Medica, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, 250117, Institute of Materia Medica, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, 250117



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