Accurate quantitative determination method for content of genotoxic impurity nitrite in medicine

Abstract

The invention relates to the technical field of nitrite testing, and especially relates to an accurate quantitative determination method for the content of genotoxic impurity nitrite in a medicine. The method comprises the following steps of drawing a standard curve and determining the nitrite content. According to the present invention, in headspace parameters, a deriving agent and nitrous acid are subjected to a diazotization reaction under the action of an inorganic acid so as to produce a diazo compound through the nitrite reaction, the diazo compound is adopted as the derivative product, and detection is performed through gas chromatography-mass spectrometry, such that the method has high detection sensitivity and the high accuracy; and by controlling the addition amounts of the inorganic acid and the deriving agent in the sample preparation process, the decomposition of a metronidazole medicine and the reaction of returning the diazo derivative product to fatty amine under the action of the inorganic acid can be avoided during a headspace parameter reaction, so that the accuracy and the recovery rate are high. The method has good repeatability and sample solution stability, and can be used for accurate quantitative determination of nitrites.

Description

technical field [0001] The invention relates to the technical field of nitrite testing, and more specifically, the invention relates to an accurate quantitative determination method for the content of nitrite, a genotoxic impurity in medicine. Background technique [0002] Metronidazole, an antibiotic and antiprotozoal agent. It is mainly used to treat or prevent systemic or local infections caused by anaerobic bacteria, such as anaerobic bacterial infections in the abdominal cavity, digestive tract, female reproductive system, lower respiratory tract, skin and soft tissues, bones and joints, etc. Inflammation of the meninges, meningeal infection, and colitis caused by antibiotics are also effective. Tetanus is often treated with tetanus antitoxin (TAT). It can also be used for oral anaerobic infection. [0003] Metronidazole injection may contain a small amount of nitrite degradation product nitrite, of which nitrite is a highly toxic substance, so in order to ensure saf...

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Problems solved by technology

[0004] Although there are some test methods for nitrite at present, such as ion chromatography, etc., they are generally used for the detection of nitrite in water systems, and the test method of ion chromatography is to detect the concentration of silver nitrite ions by conductivity, but it is easy Affected by chloride ions, etc., causing false positive results

And the method that adopts gas chromatography-mass spectrometry also has at present, as CN108008033A, but is applicable to the detection of water body, and when measuring the detection of nitrite in metronidazole, because the decomposition of possible metronidazole and use in detection process The target product, such as diazo, has poor stability, which will have an adverse effect on the determination of nitrite in metronidazole, making it difficult to obtain nitrite determination results with good accuracy, repeatability, and stability.

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