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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

Tingting Liang, Shun Liu, Fang Wang, Jiamei Gu, Yang Lu, Weike Chen, Cunyu Li, Yunfeng Zheng, Guoping Peng

J Chromatogr B Analyt Technol Biomed Life Sci. 2018 Jan 1;1072:205-210.

PMID: 29179061

Abstract:

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 6.5mM 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 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 (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.

Chemicals Related in the Paper:

Catalog Number Product Name Structure CAS Number Price
AP69567108 N-Methyl-1-deoxynojirimycin N-Methyl-1-deoxynojirimycin 69567-10-8 Price
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