Overview[1]
The impurity UDPC in Citicoline Sodium Injection is chemically called uridine diphosphate choline (UDPC). The two lone pairs of electrons of the two nitrogens on the pyrimidine ring of Citicoline Sodium Choline do not contain dipropylene glycol butyl ether. Conjugation, under acidic conditions, its nitrogen is combined with hydrogen ions, which facilitates the departure of amino ions (-NH3+), and water is replaced as a nucleophile, and finally isomerized into the impurity uridine diphosphate choline. Therefore, achieving effective separation between sodium citicoline and its impurity uridine diphosphate choline is of great significance for determining the amounts of sodium citicoline and each impurity. Currently, the field is still looking forward to an effective method for controlling the quality of Citicoline Sodium Injection, especially a method that can quickly and accurately analyze the content of the impurity uridine diphosphate choline in Citicoline Sodium Injection.
Content determination[1]
A method for the analysis and detection of uridine diphosphate choline (UDPC) in pharmaceutical preparations containing sodium citicoline. This analytical detection method is an effective method that can be used to control the quality of sodium citicoline. Using specific chromatographic analysis conditions, including the use of a C18 chromatographic column, and the use of high-performance liquid chromatography for the separation and determination of relevant impurities in citicoline sodium injection using phosphate buffer-methanol, the concentration of citicoline sodium can be effectively achieved. Isolation and determination of the impurity uridine diphosphate choline. After repeated tests, it was found that using ODS-3 (model C18, column length (Take 0.01mol/L tetrabutylammonium hydroxide solution and adjust the pH value to 4.5 with phosphoric acid) and mix in equal volumes)]-methanol (the volume ratio of the two is 95:5) as the mobile phase, which can remove the impurity citicoline sodium and uridine Effective separation of choline diphosphate enables accurate control of the quality of citicoline sodium. The technical solution is: an analysis and detection method for uridine diphosphate choline in pharmaceutical preparations containing sodium citicoline. The analytical detection method uses high-performance liquid chromatography to detect impurity urine in pharmaceutical preparations containing sodium citicoline. The analysis and detection of glycoside diphosphate choline includes the following steps:
In the first step, use high performance liquid chromatography to analyze the system suitability solution. The injection volume of the system suitability solution is 20 μl. Record the separation of the sodium citicoline peak and the 5′-cytidylic acid peak in the chromatogram. Degree;
In the second step, when the separation between the citicoline sodium peak and the 5′-cytidylic acid peak obtained in the first step is greater than 1.5, high performance liquid chromatography is used to analyze the citicoline sodium The pharmaceutical preparation sample solution and control solution, the injection volume of the pharmaceutical preparation sample solution and the control solution are both 10 μl, record the chromatogram to at least 3 times the retention time of the main component, and obtain the high performance liquid chromatography of the pharmaceutical preparation sample solution and the control solution. Analyze the chart, read and calculate at least one information from the number of impurities, types of impurities, relative amounts of impurities, and separation between each chromatographic peak;
The third step is to bring the peak area value in the high-performance liquid chromatography analysis chart obtained in the second step into the formula to calculate the uridine diphosphate bile in the pharmaceutical preparation containing citicoline sodium. The content of alkali, the formula is mass percentage of uridine diphosphate choline = (peak area of uridine diphosphate choline in the pharmaceutical preparation sample solution ÷ peak area of sodium citicoline in the control solution) × 0.5 %;
In the first and second steps, the chromatographic conditions are: the chromatographic column is an ODS-3 chromatographic column; the column temperature of the chromatographic column is 30 to 40°C; the mobile phase is phosphate buffer-methanol Mixed solution, in which the volume ratio of phosphate buffer to methanol is 95:5, the pH value of phosphate buffer is 4.3~4.7; the flow rate of the mobile phase is 0.9~1.1ml/min; a UV detector is used, and the detection wavelength is 276nm.
