A UPLC–MS/MS method for simultaneous determination of 1-deoxynojirimycin and N-methyl-1-deoxynojirimycin in rat plasma and its application in pharmacokinetic and absolute bioavailability studies

摘要

AbstractA specific, sensitive, rapid, precise, and reliable UPLC–MS/MS-based method was designed for the first time for the simultaneous determination of 1-deoxynojirimycin (DNJ) and N-methyl-1-deoxynojirimycin (N-CH3-DNJ) in rat plasma. Miglitol was served as the internal standard (IS). An MN-NUCLEODUR HILIC column was assessed to separate the two compounds by isocratic elution using acetonitrile: water with 0.05% formic acid and 6.5mM ammonium acetate (72:28, v/v) at a flow rate of 0.4mL/min. A triple quadrupole mass spectrometer was operated in the positive ionization mode using multiple reaction monitoring (MRM), and it was employed to determine transitions ofm/z164.1→110.1, 178.1→100.1, and 208.1→146.1 for DNJ, N-CH3-DNJ, and IS, respectively. The method of the two constituents was validated and the results were acceptable. The absolute bioavailability of DNJ and N-CH3-DNJ in rats was 50±9% and 62±24%, respectively. The method was then successfully used for the first time to study the pharmacokinetic behavior and absolute bioavailability of DNJ and N-CH3-DNJ in rats after intravenous (10mg/kg) and oral administration (80mg/kg). The results of this study might provide more information on preclinical pharmacokinetics and a solid basis for assessing the clinical efficacy of DNJ and N-CH3-DNJ.]]>