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

作者：Liang, Tingting; Liu, Shun; Wang, Fang; Gu, Jiamei; Lu, Yang; Chen, Weike; Li, Cunyu; Zheng, Yunfeng; Peng, Guoping^*

来源：Journal of Chromatography B-Analytical Technologies in the Biomedical and Life Sciences, 2018, 1072: 205-210.

DOI：10.1016/j.jchromb.2017.10.055

• 1-Deoxynojirimycin
• N-Methyl-1-deoxynojirimycin
• UPLC-MS/MS
• Pharmacokinetics
• Bioavailability

A 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 6.5 mM ammonium acetate (72:28, v/v) at a flow rate of 0.4 mL/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 of m/z 164.1 -> 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 (10 mg/kg) and oral administration (80 mg/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.

• 出版日期2018-1-1
• 单位南京中医药大学