Impurity detection method for 3-amino-1-adamantanol

Abstract

The invention relates to an impurity detection method of 3-amino-1-adamantanol, which is characterized in that the impurity content is detected by using high performance liquid chromatography-mass spectrometry, and after a sample to be detected is dissolved by using a diluent, the sample is injected and analyzed; a mobile phase of the high performance liquid chromatography system is a mixed solution of an aqueous solution of acid and an organic solvent, a diluent is a methanol-aqueous solution with a volume ratio of 1: 1, and a chromatographic column is a C18 chromatographic column; the mobile phase is a formic acid aqueous solution with the formic acid volume concentration of 0.1% and acetonitrile, and the flow velocity is 0.3 mL per minute; and carrying out gradient elution on the mobile phase. According to the method, impurities in 3-amino-1-adamantanol are detected through liquid chromatography-mass spectrometry, the specificity is high, the sensitivity is high, the quantitation limit is 0.016%, and the detection limit is 0.005%; meanwhile, the detection precision is improved, the method reproducibility is good, the relative standard deviation of continuous sample injection is 0.92%, and convenience is provided for analysis of 3-amino-1-adamantanol, so that the quality of 3-amino-1-adamantanol is controllable, and conditions are provided for industrial production of vildagliptin.

Description

technical field [0001] The invention relates to the field of drug analysis, in particular to a method for detecting impurities of 3-amino-1-adamantanol. Background technique [0002] Vildagliptin is an orally administered dipeptidyl peptidase-IV inhibitor developed and marketed by Novartis Pharmaceuticals Co., Ltd. It is commonly used in the treatment of type 2 diabetes. There are many synthetic methods of vildagliptin disclosed in the existing literature, wherein 3-amino-1-adamantanol is an important starting material for synthesizing vildagliptin, and the commercially available 3-amino-1- Among the adamantane alcohols, 5-amino-adamantane-1,3-diol is an impurity present. According to the ICH Q3A (Impurities in New Drug Substances) guideline, the identification and control of impurities in starting materials is required. [0003] There is no analytical method for detecting 5-amino-adamantane-1,3-diol in the prior art. [0004] The molecular weight of 5-amino-adamantane-1,...

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Problems solved by technology

[0003] There is no analytical method for detecting 5-amino-adamantane-1,3-diol in the prior art

[0004] The molecular weight of 5-amino-adamantane-1,3-diol is only 183.25, the molecular weight is small; there is no retention in liquid chromatography, and there is a peak in the dead volume, which cannot be detected; commercially available 5-amino-adamantane-1,3 - The diol reference substance is hydrochloride, which is difficult to elute in the gas phase

That is to say, the existing common chromatographic monitoring methods cannot accurately detect the content of the impurity 5-amino-adamantane-1,3-diol

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