A kind of detection method of nitrosamine compound in higenamine hydrochloride

Abstract

The invention provides a method for detecting nitrosamine compounds in higenamine hydrochloride. Octadecylsilane-bonded silica gel is selected as the filler, formic acid aqueous solution and methanol as the mobile phase, so that it contains NDMA, NDEA and other When higenamine hydrochloride as an impurity is separated by liquid chromatography, higenamine hydrochloride and other impurities will not affect the solution of the target NDMA and NDEA on the chromatographic column during the molecular dissociation process of NDMA and NDEA under this condition. Dissociation selectivity causes interference, and the theoretical plate number of NDMA peak is not less than 6014 in the method of the present invention, and the theoretical plate number of NDEA peak is not less than 120325, and symmetry factor is all not more than 2.0, and the recovery rate of detection method of the present invention is in Between 85% and 102%. The system applicability, specificity, precision, quantitative limit and detection limit, linearity and range of the method all meet the requirements, the separation effect is good, the operation detection is high, 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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