Technical requirements for development and calibration of Chinese medicine reference materials (2)

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(1) Investigation on the acceptance of drug standards

The research and development varieties of reference medicinal materials are mainly based on the current national drug standards, including: "Chinese Pharmacopoeia" (current edition), the former State Food and Drug Administration National Drug Standards, "New Drug Standardization Standards", and the original State Food and Drug Administration "national standards compilation medicine (medicine local standards rising national standards section)," the former Ministry of health drug standard "Chinese medicine prescription preparations," the former Ministry of health drug standard "drug positive standard" and so on

(2) Collection and storage of reference medicinal materials

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(3) Pharmacognosy identification of reference medicinal materials

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(4) Physical and chemical calibration of reference medicinal materials

The sample for physical and chemical calibration must be the finished powder that has passed the pharmacognosy identification and crushed the entire batch of raw materials

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(1) Inspection item: Impurities should be removed according to the standard

(2) Assay items: Assay shall be carried out in accordance with the regulations of medicinal materials standards, and shall comply with the regulations of medicinal materials standards

(3) Physical and chemical testing of the changed varieties: the first batch of reference medicinal materials must be used as a control, and the monomer Chinese medicine chemical reference materials shall be used as the control at the same time as possible.
The results of thin-layer chromatography must be consistent with the first batch of chromatograms to ensure the continuity of the reference medicinal materials
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Technical requirements for the development and calibration of control extracts

Control extract is a type of non-monomeric component control substance, including medicinal material control extract and volatile oil control substance, used for thin layer chromatography or other chromatographic identification or content determination (labeled content control extract)
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(1) Source, extraction, separation and purification of raw materials

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The source of the raw materials should be determined according to the types of medicinal materials or proprietary Chinese medicines specified in the national standards.
The raw materials of the medicinal materials should generally be authentic medicinal materials of mainstream commodities, or cultivated high-quality Chinese medicines that meet the requirements of GAP specifications.
At the same time, the collection time, location and processing method should be fixed
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The extraction process should be based on the drug standards and the effective ingredients or effective parts and its physical and chemical properties, and at the same time, according to the extraction principle and experimental analysis results, select the appropriate extraction method, design a reasonable process route, and determine the design basis of the extraction process
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After the preliminary determination of the extraction process route, the factors that may affect the extraction effect should be fully considered, scientific and reasonable experimental design should be carried out, accurate, simple, representative, and quantifiable evaluation indicators and methods should be adopted to optimize the reasonable extraction process conditions
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(2) Separation and purification research

The separation and purification process includes two aspects: one is to select the corresponding separation method and conditions according to the nature of the crude extract to obtain an effective extraction material; the other is to remove invalid and harmful components, and try to retain the effective ingredients or effective For the part, various purification and refining methods can be used to enrich the target components in a targeted manner
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(3) Physical and chemical inspection

It mainly includes general physical and chemical identification, chromatographic or spectral identification, and the establishment of fingerprint or characteristic maps
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Chromatographic identification should be compared with related chemical reference substances, reference medicinal materials or pharmaceutical preparations to determine their consistency
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At the same time, in order to ensure consistency between batches of reference materials, their fingerprint or characteristic maps should be established
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The inspection items include impurities, moisture, ash, acid-insoluble ash, heavy metals, arsenic salts, pesticide residues, related toxic components and other necessary inspection items
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The corresponding limits shall be specified based on the measurement results of more than three batches of samples
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Establishment of fingerprint or characteristic pattern.
For fingerprint or characteristic pattern detection control extract, HPLC or GC method should be used to establish fingerprint pattern or characteristic pattern, and confirm the chromatographic peak with clear structure as much as possible, with fingerprint pattern attached.
Or feature map
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(4) Fixed value of multi-component components

For reference extracts, for the main active ingredients or characteristic ingredients and other ingredients with declared value, the method of collaborative calibration should be adopted, and the collaborative unit requires more than 3
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The results of the collaborative calibration are determined after mathematical statistics.
At the same time, the durability of the control extract after the determination should be investigated, including the analysis and determination conditions, different laboratories, and the determination of related preparations
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