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Pharmacokinetic Study of Hypaphorine, a Potential Agent for Treating Osteoclast-based Bone Loss, on Rats Using LC-MS/MS

机译:Pharmacokinetic Study of Hypaphorine, a Potential Agent for Treating Osteoclast-based Bone Loss, on Rats Using LC-MS/MS

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摘要

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 x 4.6 mm, 5 mu m). 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 (R-2 = 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.

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