1. General situation :
1. Product name and code: Product name: Benoylate
2. Molecular formula : C 17 H 15 NO 5 Molecular weight: 313.31
3. Structural formula:
2. Characters :
1. This product is white crystal or crystalline powder; it is odorless.
2. This product is easily soluble in boiling ethanol, soluble in boiling methanol, slightly soluble in methanol or ethanol, and insoluble in water.
3. Melting point: melting point of The this product (General Rule 0612) is 177～181℃.
4. Absorption coefficient: take this product, accurately weigh it, dissolve it with absolute ethanol and dilute it quantitatively to make containing about 7.5μg per 1ml, a solution ultraviolet -visible spectrophotometry (general rule 0401 measured by ), at a wavelength of 240nm Measure absorbance, absorption coefficient Is 730～760.
3. identification:
1. Take about this product 0.2g of , add sodium hydroxide test solution 5ml of , boil, let cool, filter, add appropriate amount of hydrochloric acid to the filtrate until it is slightly acidic, add ferric chloride test solution, and the color will 2 drops of appear purple.
2. The infrared light absorption spectrum of this product should be consistent with the control spectrum (spectrum set 42).
3. Take about this product 0.1g of , add dilute hydrochloric acid 5ml of , boil, let cool, filter, the filtrate shows the identification reaction of aromatic first amines (General Rule 0301).
4.check:
1. Chloride: Take this product 2.0g of , add water 100ml of , heat and boil, let cool, add water to 100ml , shake well, filter, take filtrate 25ml of , check according to law (General Rules 0801), and make with standard sodium chloride solution 5ml The comparison of the prepared control solution should not be more concentrated (0.01%).
2. Sulfate: Take of the remaining filtrate under the chloride item 25ml and check it according to the law (General Rule 0802). Compared with 1ml of standard potassium sulfate solution the control solution made of , it should not be more concentrated ( 0.02%).
3. P-Aminophenol: Take this product 1.0g of , add 20ml of methanol solution (1→2), shake well, add 1ml of alkaline sodium nitrosoferricyanide test solution, shake well, place for 30 minutes, no blue-green color .
4. Free salicylic acid: Take this product 0.1g of , add ethanol 5ml of , after heating to dissolve, add an appropriate amount of water, shake well, filter into a 50ml colorimetric tube, add water to make 50ml, immediately add a freshly prepared dilute ferric ammonium sulfate solution ( Take 1mol/L hydrochloric acid solution 1ml of , add ferric ammonium sulfate indicator solution 2ml of , and add an appropriate amount of water to make 100ml ) 1ml , shake well, if the color develops within 30 seconds, compare with the control solution (precisely weigh 0.1g salicylic acid and place in 1000ml In the measuring flask, add glacial acetic acid to dissolve in water 1ml of , shake well, add appropriate amount of water to the mark, shake well, accurately measure 1ml , add ethanol 5ml of and water 44ml of , then add the freshly prepared dilute ferric ammonium sulfate solution 1ml of , shake Even) comparison, not deeper ( 0.1%).
5. Related substances: new system for temporary use. Take this product, add methanol to dissolve and dilute to make a solution containing 0.4mg per 1ml, shake it up, as the test solution; accurately measure 1ml, put it in a 100ml measuring flask, dilute to the mark with methanol, shake it up, as Control solution. Take another appropriate amount of paracetamol reference substance, add methanol to dissolve and dilute to make per 1ml containing a solution 10μg , as the reference substance solution. According to the chromatographic condition test under the content determination item, accurately measure 10μl each of the test solution, reference solution and control solution and inject them into the liquid chromatograph. Record the chromatogram to 2.5 retention time of the main component peak times the . If there is a chromatographic peak in the chromatogram of the solution that is consistent with the retention time of the main component peak of the reference solution, its peak area shall not be greater than main peak area of the reference solution 0.1 times (0.1%) of the ; other single impurity peak areas shall not be greater than the main peak area of the reference solution 0.5 times (0.5%); the sum of the peak areas of each impurity should not be greater than the main peak area of the control solution (1.0%).
6. Loss on drying: Take this product and at dry it to constant weight 105°C. The weight loss should not exceed 0.5% (General Rule 0831).
7. Residue on ignition: Take this product 1.0g of and inspect according to law (General Rule 0841), and the remaining residue shall not exceed 0.1%.
8. Heavy metals: Take the residues left over under the item of residues on ignition and inspect them in accordance with the law (General Rule 0821 Law 2), and the content of heavy metals shall not exceed 10 parts per million.
9. Microbial limit inspection: In accordance with the law (General Rule 1105 and General Rule 1106), the total number of aerobic bacteria in each 1g of the test product must not exceed 2000cfu, the number of molds and yeasts must not exceed 200cfu, and Escherichia coli must not be detected.
5. Assay Determine :
according to high performance liquid chromatography ( General Principle 0512).
4.7.1 Chromatographic conditions and system suitability test: use octadecylsilane bonded silica as filler; use water (adjust pH to 3.5 with phosphoric acid)-methanol (44:56) as mobile phase; detection wavelength is 240nm . The number of theoretical plates should not be less than 3000 calculated based on the benoxate peak, and the resolution between the benoxate peak and the adjacent impurity peaks should meet the requirements.
4.7.2 Determination method: take this product, accurately weigh, add methanol to dissolve and quantitatively dilute to make a solution containing about 0.4mg per 1ml, shake it, accurately measure 10μl into the liquid chromatograph, record the chromatogram; Take the benolate reference substance, measure it in the same way, and calculate it with the peak area according to the external standard method.
This product is calculated as a dry product, and the content of C 17 H 15 NO 5 should be 99.0% to 102%.
6. Inspection items and limits:
project | Statutory standard | Internal control standards |
Melting point | The limit is 177～181℃. | The limit is 177.5～181 ℃. |
Absorption coefficient | Absorption coefficient (  ) Is 730～760. | ---------- |
Identify | (1), (2), (3) should meet the requirements. | ---------- |
chloride | Compared with the control solution, it should not be more concentrated (0.01%). | ---------- |
Sulfate | Compared with the control solution, it should not be more concentrated (0.02%). | ---------- |
relative substance | meets the requirments. | ---------- |
P-aminophenol | meets the requirments. | ---------- |
Free salicylic acid | Compared with the control solution, it should not be deeper (0.1%). | ---------- |
Loss on drying | The weight loss shall not exceed 0.5%. | The weight loss shall not exceed 0.4%, which shall comply with the regulations. |
Residue on ignition | The remaining residue shall not exceed 0.1%. | ---------- |
Heavy metal | Contain no more than 10 parts per million of heavy metals. | ---------- |
Microbial Limit | The total number of aerobic bacteria <2000cfu/ g ; The number of molds and yeasts <200cfu/ g ; Escherichia coli cannot be detected. | The total number of aerobic bacteria <800cfu/ g ; The number of molds and yeasts <80cfu/ g ; Escherichia coli cannot be detected. |
Assay | According to the dry product, the content of C 17 H 15 NO 5 should be 9 9.0 % ～102% | According to the calculation of dry product, the content of C 17 H 15 NO 5 should be 9 9.2 % ～102% |
7. Sampling regulations :
see SOP.QC-QY-004 "Standard Operating Procedures for Sampling of Finished Products".
8. Inspection method:
see SOP.QC-CJ-058 " Benoylate Standard Operating Procedures for Inspection of Finished Products ".
9. Packaging form:
25Kg/bag, the inner packaging is a medicinal low-density polyethylene bag, and the outer packaging is a paper-plastic composite bag.
10. Storage conditions and precautions :
shading, sealed and stored.
11. Validity period : 48 months.
