Foreword: for some products, if the intermediate inspection institute does not provide the reference substance, or the intermediate inspection institute does not have the stock, it can calibrate the working reference substance (standard substance) by itself. Using the calibrated working reference substance not only meets the legal requirements, but also saves the cost. The company can also calibrate the working standard for customers and provide relevant documents. The following is "standard operating procedures for calibration of working standards (reference materials)", for reference.

1. Objective: to establish a management procedure for working standards. Carry out standardization verification on self-made working standards to ensure the equivalence between working standards and basic standards, so as to ensure the accuracy of determination results.
2. Scope: all working standards used in QC inspection.
3. Responsibility: QC.
4. Content:
4.1 legal standards and calibration test methods: legal standards refer to the current batch numbers of USP, EP, CP and other standards. To select the test method of the Pharmacopoeia. Different Pharmacopoeia test methods are used for different standards.
4.2 establishment of quality standards for working standards
The quality standard of the working standard should be established first. The general principle is to establish it on the basis of the original legal standard, which should be stricter than the pharmacopoeia standard. To increase the content of main components and reduce the limit of relevant substances, other items can remain unchanged.
4.3 source and calibration of working standards
4.3.1 source of working standard: released API with good quality recently produced; Purchased compounds meeting the content requirements.
4.3.2 calibration inspection shall be carried out according to the quality standard of the working standard. Full inspection shall be conducted during the first calibration, and only the content shall be measured during the re calibration. After the calibration or re calibration is qualified and approved, it can be used as a working standard. If the released API with good quality produced recently is selected as the working standard, only the content can be determined during calibration.
4.3.3 when there are BP, USP or EP standards
4.3.3.1 if USP working standard is calibrated, the legal standard of USP current batch number shall be used for calibration, and so on.
4.3.3.2 calibration process of working standard
A if necessary, the standard shall be pretreated (such as drying);
B select two skilled personnel for calibration;
C weigh one legal standard and three samples respectively;
D. system adaptability test shall be qualified;  
E the RSD of the content results of the same analyst shall not be greater than 0.5%, and the relative deviation of the average value of the content results of different analysts shall not be greater than 0.3%;
F is the calibration result after averaging.  
4.3.4 when there are no BP, USP or EP standards
4.3.4.1 when there is no official standard, the self-made working standard shall be standardized according to the following methods: weigh 5 samples of the same batch number, inject each sample twice, the RSD of the content result shall not be greater than 1.0%, and the calculated result shall be taken as the official purity value of the self-made standard.
4.3.4.2 each parallel sample result of this method can be used only when it meets the established indicators. At this time, the total average value can be used as the purity value of the self-made standard. However, the effect of water, residual solvent or residue content on the results should be considered and adjusted appropriately.
4.4 validity period and re bid date of the working standard.
4.4.1 the validity period of the working standard is two years (calculated from the calibration date, shorter than the validity period of the API).
4.4.2 the content of working standard shall be re standardized once every six months.
4.4.3 batch number of working standard add -rs to the batch number of API as the batch number of working standard.