Optimization of Determination Method for Related Substances in Nitroglycerin Solution and Its Preparations
Objective To optimize the determination method of related substances in nitroglycerin solution and its preparations.Methods The mobile phase in the high-performance liquid chromatography(HPLC)method of the current standard Chinese Pharmacopoeia(2020 Edition,Volume Ⅱ)was replaced,the gradient elution method was adopted,and the preparation method of the system suitability solution was optimized.The chromatographic column was the Ecosil 120-5-C18 AQ column(250 mm×4.6 mm,5 µm),the mobile phase was water-methanol(gradient elution),the flow rate was 1.0 mL/min,the detection wavelength was 215 nm,the column temperature was 30℃,and the injection volume was 20 µL.Results The limit of quantification and limit of detection of nitroglycerin were 0.21 µg/mL and 0.07 µg/mL respectively.The RSDs of precision and stability tests were both lower than 2.0%.After optimization of the HPLC conditions,the nitroglycerin was successfully separated from the known impurities such as 2-glycerol mononitrate,1-glycerol mononitrate,1,3-glycerol dinitrate,1,2-glycerol dinitrate;the deduction of free nitrate ions was clarified;based on the British Pharmacopeia 2023 and the content determination of related substances in samples,it was proposed that all four known impurities should be not over 0.5%except for the nitrate ion,the other single maximum impurity should be not over 0.1%in the solution and 0.5%in the injection and tablets,the total amount of impurities should be not over 1.5%in the solution and injection and 2.0%in the tablets.Conclusion The established method is accurate,rapid,and specific,which is suitable for the inspection of related substances in nitroglycerin solution and its preparations.This study provides a reference for strengthening the quality control and further revision of the quality standards of this product.
nitroglycerin solutionnitroglycerin injectionnitroglycerin tabletsrelated substancesHPLCquality standard
万方数据
维普
