Analysis on the Function of Clarity Inspection Method in Drug Quality Inspection

Clarity is to check the turbidity of the drug solution, that is, turbidity. The clarity check method is one of the drug impurity analysis methods, mainly to check whether there are insoluble impurities in the drug solution. It can be used as the quality control of the raw material for injection and its injection project. Pure and high-quality injection drugs should be clear and transparent after dissolution. Unless the drug itself is a suspension or emulsion, the clarity inspection method is an extremely sensitive and intuitive test index.

There may be dispersed and insoluble fine particles in some drug solutions. These particles may be intermediates in the production process, the drug itself or its insoluble decomposition products, insoluble impurities, contaminated foreign matter or microorganisms, and some that form milk with water. Turbid solvents, etc. The clarity check method can be used for drug impurity analysis. It compares the drug solution with the specified turbidity standard liquid phase to check the clarity of the solution. The clarity inspection method can be inspected by visual inspection method and instrumental method.

1. Two methods of clarity check

In specific experiments, the visual method is the first choice for clarity inspection. When the visual method cannot be used for effective judgment, the instrument method can be used to judge the result. However, the clarity inspection of colored solutions still needs to be judged by visual method. The instrument measurement method provides three methods, namely, transmitted light, scattered light, and transmitted light-scattered light comparative measurement mode (ratio turbidity mode). The principle is that when the light source illuminates the liquid surface, there is a certain correlation between the transmitted light intensity, scattered light intensity, the ratio between the transmitted light intensity and the scattered light intensity and the turbidity of the test sample. By measuring the transmitted light intensity, The ratio of scattered light intensity, transmitted light intensity and scattered light intensity reflects the turbidity of the test product. Medicilon’s analytical chemistry and purification and separation teams provide customers with high-quality analysis and purification and separation services, including the use of HPLC and other technologies to separate and supervise impurities in starting materials, intermediates, APIs and pharmaceutical products, and collect complete 1D/2D NMR, LCMS, EA, HRMS, IR, UV and other data, the structure identification of the separated impurities, etc.

2. Application of Clarity Check Method

Turbidity precipitation will occur when high-concentration vancomycin is mixed with heparin, but this phenomenon will not occur when low-concentration vancomycin is mixed with heparin, and the sterilization effect of antibiotics with too low concentration is unknown. In order to study the stability and in vitro antibacterial activity of the mixture of vancomycin and heparin, the researchers mixed vancomycin and heparin sodium injection into a mixture containing different concentrations of vancomycin and the same concentration of heparin, and stored in a 37 incubator Within 0 min, 15 min, 30 min, 24 h, 48 h, take it out in sequence, use naked eye observation and check the clarity of the mixed solution on a clarity tester[1]

The researchers selected a mixture of specific concentrations, and compared the mixture and the same concentration of vancomycin physiological saline solution to the standard reference strain Staphylococcus aureus (ATCC 29213) at 0h, 2h, 8h, 24h, and 48h. Bacterial circle. It was found that as the concentration of vancomycin decreased, the turbidity of the mixture gradually decreased until it became clear. The study found that the turbidity of vancomycin and heparin is related to the concentration of vancomycin. Vancomycin mixture with a concentration of 10mg/ml has stable properties and obvious bacteriostasis. It can be used as catheter-related bacteremia, especially It is a sealing solution for catheter-related bacteremia caused by Staphylococcus aureus infection.

Some researchers have established a method for checking the clarity of lovastatin, and at the same time inspected the clarity results of several batches of lovastatin raw materials in China, and evaluated their effectiveness based on the results [2]. Acetonitrile was used as the solvent and compared with the turbidity standard solution after dissolution. Measure the specific rotation and content of the raw materials at the same time, and analyze the three results. The results found that among the 16 batches of lovastatin raw materials from 8 manufacturers, 6 batches of samples from 3 manufacturers had a higher turbidity than No. 2 turbidity standard solution, and the remaining samples were clear at No. 1. There is a correlation between the clarification and the content of the product and the determination of specific rotation. The study strongly proved that the inspection and control method for clarity is applicable and necessary, and can effectively monitor the drug production process to control drug quality.

At present, the clarity check method has been collected by some national pharmacopoeias. When applying it as a drug impurity analysis method, it should be noted that the clarity check of most drugs uses water as the solvent, but some or both use acid, alkali or Organic solvents such as ethanol, methanol, and propanol are used as solvents. At the same time, it should be noted that the alkali metal salts of organic acids emphasize the use of freshly boiled water, because carbon dioxide dissolved in the water will affect the clarity of the solution. If the first method cannot accurately determine the difference in clarity between the two, the second method can be used for determination and the determination results are used for determination.

[1] Study on the stability and in vitro antibacterial activity of vancomycin and heparin mixture [J].

[2] Evaluation of the effectiveness of lovastatin clarity check [J].