摘要
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.
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.
基金
supported by USC-Taiwan Center for Translational Research
the Daniel Tsai Family Fund
Boyd & Elsie Welin Professorship
by the Department of Defense Prostate Cancer Research Program Grant W81XWH-12-1-0282
