Method for detecting nitrosamine compounds in higenamine hydrochloride

Abstract

The invention provides a method for detecting nitrosamine compounds in higenamine hydrochloride, which comprises the following steps: selecting octadecylsilane chemically bonded silica as a filler, and formic acid aqueous solution and methanol as mobile phases, so that when the higenamine hydrochloride containing NDMA, NDEA and other impurities is separated through liquid chromatography, the higenamine hydrochloride and other impurities cannot cause interference on the dissociation selectivity of the chromatographic column on target objects NDMA and NDEA in the dissociation process of NDMA and NDEA molecules under the conditions. The number of theoretical plates of an NDMA peak in the method is not smaller than 6014, the number of theoretical plates of an NDEA peak in the method is not smaller than 120325, symmetry factors are not larger than 2.0, and the recovery rate of the detection method ranges from 85% to 102%. According to the method, the system applicability, specificity, precision, quantitation limit, detection limit, linearity and range all meet the requirements, the separation effect is good, operation detection is achieved, and the method sensitivity is high.

Description

technical field [0001] The invention relates to the technical field of chemical detection and analysis, in particular to a method for detecting nitrosamine compounds in higenamine hydrochloride. Background technique [0002] The chemical name of higenamine hydrochloride is 1-(4-hydroxybenzyl)-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline hydrochloride. Higenamine hydrochloride has cardiac β-adrenergic receptor stimulatory effect, and its action on α-adrenoceptor can relax blood vessels and anti-platelet aggregation activity, and can also inhibit the inducible type in macrophages, vascular smooth muscle and other cells. Expression of nitric oxide synthase (iNOS) and production of nitric oxide (NO). As a reagent for myocardial perfusion imaging under stress, higenamine hydrochloride can increase the heart rate, lower the diastolic blood pressure, improve the conduction function of the sinus node, have a good effect on sinus bradycardia, and significantly enhance the myocardial...

AI Technical Summary

Problems solved by technology

Its formation mechanism is relatively complicated and may be formed in various ways, such as the risk of introducing nitrosamine impurities from the process, the risk of introducing pollution, and the use of materials contaminated by nitrosamine impurities in the production process of APIs (initial materials, intermediates, solvents, reagents, catalysts, etc.) may bring the risk of nitrosamine impurities, and the use of recycled materials may also introduce the risk of nitrosamine impurities. Different varieties are produced in the same production line, and cross-contamination may also become a Potential Causes of Introduced Nitrosamine Impurities

However, since the acceptable limit of nitrosamine impurities in the human body is relatively good, the detection and control of trace impurities is relatively difficult

In order to ensure the safety and quality control of drugs and to achieve effective risk control, it is necessary to control the impurities of nitrosamines in higenamine hydrochloride. However, the control of nitrosamines in drugs is usually trace order of magnitude, and the limit of various impurities existing in higenamine hydrochloride is far beyond the limit of nitrosamine compounds, so how to overcome the impact of existing substances in higenamine hydrochloride on nitrosamines The interference of compound impurity detection is the difficulty of developing the detection of nitrosamine impurities in higenamine hydrochloride, and the detection method of nitrosamine impurities in higenamine hydrochloride has not been reported in the prior art

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