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Quantification and pharmacokinetic study of tumor-targeting agent mhI148-clorgyline amide in mouse plasma using liquid chromatography-electrospray ionization tandem mass spectrometry

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Journal of Pharmaceutical Analysis 2018年第3期8卷 153-159页

作者： Zhijun Wang Bogdan Z.Olenyuk Jean Chen Shih Jeffrey Wang Center for Advancement of Drug Research and Evaluation College of Pharmacy Western University of Health Sciences Department of Pharmaceutical Sciences College of Pharmacy Marshall B.Ketchum University Department of Pharmacology and Pharmaceutical Sciences School of Pharmacy Department of Cell and Neurobiology Keck School of Medicine USC-Taiwan Center for Translational Research University of Southern California Department of Pharmaceutical Sciences College of Pharmacy Western University of Health Sciences

A high-performance liquid chromatography-electrospray ionization tandem mass spectrometric （HPLC- ESI-MS/MS） method was developed for the quantification of mhl148-clorgyline amide （NMl-amide）, a novel tumor-targeting monoamine oxidase A inhibitor, in mouse plasma. The method was validated in terms of sensitivity, precision, accuracy, recovery and stability and then applied to a pharmacokinetic study of NMl-amide in mice following intravenous administration. NMl-amide together with the internal standard （IS）, mhI-148, was extracted by protein precipitation using acetonitrile. Multiple reaction monitoring was used for quantification of NMl-amide by detecting m/z transition of 491.2-361.9, and 685.3-258.2 for NMl-amide and the IS, respectively. The lower limit of quantification （LLOQ） of the HPLC- MS/MS method for NMl-amide was 0.005 μg/mL and the linear calibration curve was acquired with R2〉 0.99 in the concentration range of 0.005-2μg/mL. The intra- and inter-day precisions of the assay were assessed by percentage of the coefficient of variations, which was within 9.8% at LLOQ and 14.0% for other quality control samples, whereas the mean accuracy ranged from 86.8% to 113.2%. The samples were stable under storage and experimental conditions. This method was successfully applied to a pharmacokinetic study in mice following intravenous administration of 5 mg/kg NMl-amide.

关键词： mh1148-clorgyline HPLC Mass spectrometry Pharmacokinetics

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