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Combinatorial Chemistry & High Throughput Screening

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ISSN (Print): 1386-2073
ISSN (Online): 1875-5402

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Research Article

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

Volume 25, Issue 11, 2022

Published on: 04 January, 2022

Page: [1889 - 1896] Pages: 8

DOI: 10.2174/1386207325666211005144429

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Abstract

Aims and Objectives: A high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for determining hypaphorine, a potential agent for treating osteoclast- based bone loss, was developed and validated 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 transitions from protonated precursor ion [M + H]+ to the particular daughter ion were acquired using selected reaction monitoring (SRM). The mass transitions of hypaphorine and IS were found to be 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 pharmacokinetic 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.

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