Calibration of Reference Substances and Standards in the Central Inspection Institute
The purity determination method should be chromatographic method, and two or more different separation mechanisms or different chromatographic conditions and validated chromatographic methods should be used to verify and compare each other. At the same time, a diode array detector or other suitable methods should be used to detect the purity of the chromatographic peak of the HPLC method, and then the purity of the reference substance (standard) raw materials should be determined by statistical analysis according to the measurement results.
For drugs with single components and high purity, the first choice for the calibration method of reference substances (standards) should be the volume method that can be equivalent conversion, high precision, simple and fast operation. Different volume analysis methods can be selected according to the functional groups and chemical properties of the drug molecules, but the following conditions should be met:
(1) The reaction proceeds completely in one direction.
(2) The reaction is rapid, and the reaction rate can be increased by heating or adding a catalyst if necessary.
(2) The reaction is rapid, and the reaction rate can be increased by heating or adding a catalyst if necessary.
(3) Coexisting substances must not interfere with the main drug reaction, or can be eliminated by appropriate methods.
(4) The method of determining the equivalence point should be simple and sensitive.
(5) The reference material used in the standardized titration solution is easily available, and meets the requirements of high purity, constant composition, and chemical formula, and stable properties (no side reactions occur during calibration).
The choice of calibration method should pay attention to the following matters:
(1) The dosage of the test sample should meet the requirements of titration accuracy (about 20ml of titration solution is consumed).
(2) The judgment of the titration end point should be clear and a titration curve should be provided. If the indicator method is used, its discoloration should be considered, and the final point color should be calibrated by the potentiometric method.
(3) In order to rule out the influence of impurities mixed with other reagents on the measurement results, or to facilitate the calculation of the residual titration method, the method of "correcting the titration results with a blank test" can be used;
(4) The process of deriving the titration (using four significant digits) should be given.
The calibration results should be statistically analyzed according to the measurement results of no less than 15 groups in each of the three or more laboratories, and the results after removing outliers and suspicious values should be reported with confidence limits.
If the drug does not have a capacity method that can be equivalent to the equivalent conversion and meets the requirements, the raw materials can be repeatedly purified. After the purity is determined by chromatography, the theoretical content after deducting the relevant substances, incandescent residues, moisture, and volatile solvents is determined as the standard content, and the reference substance (standard) is replaced and the quantity value is transferred as a benchmark.
