Acetaminophen is an organic compound with chemical formula CeightHnineNOtwoIt is a metabolite of phenacetin in the body. It can reduce the synthesis and release of prostaglandin PGE1, bradykinin and histamine by inhibiting prostaglandin synthetase in the hypothalamic thermoregulatory center.PGE1 mainly acts on the nerve center, and its decrease will lead to the decrease of the central temperature setting point, and the body surface temperature sensor will feel relatively hot, and then through nerve regulation, it can cause peripheral vascular expansion and sweating to achieve the antipyretic effect. Its inhibitory effect on prostaglandin synthesis in the central nervous system is similar to aspirin, but its anti-inflammatory effect is weak.It has no effect on platelet and coagulation mechanism.
On October 27, 2017, the list of carcinogens released by the International Agency for Research on Cancer of the World Health Organization (WHO) was preliminarily sorted out for reference. Paracetamol was included in the list of three types of carcinogens.[3]
On January 3, 2023, the State Food and Drug Administration approved 13 symptomatic drugs for coronavirus infection, including acetaminophen, to market through the fast review channel.[5]
Chinese name
Acetaminophen
Foreign name
Paracetamol；acetaminophen[6]
alias
N-Acetaminophen、4-Acetaminophenol
chemical formula
CeightHnineNOtwo
molecular weight
one hundred and fifty-one point one six three
CAS registration
103-90-2
EINE
203-157-5
melting point
168 to 172 ℃
atlas
Science popularization in China
Committed to authoritative science communication
The certification expert of this term is
Zhang Zheng|Pharmacist in charge
Pharmacy Department of Beijing Chaoyang Hospitalto examine
Qiu Kui|Pharmacist in charge
Pharmacy Department of Beijing Chaoyang Hospitalto examine
Solubility: soluble in methanol, ethanol, dichloroethylene, acetone and ethyl acetate, slightly soluble in ether and hot water, almost insoluble in cold water, insoluble in petroleum ether, pentane and benzene[4]
Molecular structure data
Molar refractive index: 42.40
Molar volume (cmthree/mol）：120.9
Isotonic specific volume (90.2K): 326.0
Surface tension (dyne/cm): 52.8
Polarization (10-24cmthree）：16.81[4]
Calculate chemical data
Reference value for drainage parameter calculation (XlogP): None
Number of hydrogen bond donors: 2
Number of hydrogen bond receptors: 2
Number of rotatable chemical bonds: 1
Number of tautomers: 6
Topological molecular polar surface area: 49.3
Number of heavy atoms: 11
Surface charge: 0
Complexity: 139
Number of isotope atoms: 0
Determine the number of atomic structure centers: 0
Number of uncertain atomic structure centers: 0
Determine the number of chemical bond structure centers: 0
Number of uncertain chemical bond structure centers: 0
Number of covalent bond units: 1[4]
Brief Introduction to Drugs
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indication
It is used for cold, fever, arthralgia, neuralgia, migraine, cancer pain and postoperative pain relief.It can also be used for patients who are allergic to, intolerant of or unsuitable for aspirin (chickenpox, hemophilia and other bleeding diseases).
Usage and dosage
1. Oral
0.3-0.6g once, 0.6-0.8g per day, the daily dose should not exceed 2g, and a course of treatment should not exceed 10 days;Children under 12 years old should take 1.5g daily.
2. Intramuscular injection
0.15~0.25g once.
3. Rectal administration
0.3-0.6g once, 1-2 times a day.
Adverse reactions
A few cases may have allergic dermatitis (rash, skin itching, etc.), agranulocytosis, thrombocytopenia, methemoglobinemia, anemia, liver and kidney function damage, etc.
matters needing attention
Short term use generally does not cause gastrointestinal bleeding.It shall be used for antipyretic for no more than 3 consecutive days and for pain relief for no more than 5 days.Excessive dosage can cause liver damage, and even coma or death in severe cases.Do not drink alcohol or alcoholic beverages.
Drug contraindication
It is forbidden for those allergic to this product.Use with caution in patients with liver and kidney dysfunction.Pregnant women and lactating women should use it with caution.
Drug interaction
1. Because it can reduce the synthesis of coagulation factors in the liver and enhance the role of anticoagulants, the dosage should be adjusted according to the prothrombin time when it is used for a long time or in large quantities.
2. When combined with ziftodine, aspirin or other NSAIDs, the renal toxicity was significantly increased.
Note: The above contents are only for introduction. Drug use must be carried out by regular hospitals under the guidance of doctors.
Pharmacopoeia information
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essential information
This product is 4 '- hydroxyacetanilide, calculated as dry product, containing CeightHnineNOthreeIt should be 98.0%~102.0%.
character
This product is white crystal or crystalline powder, odorless.
This product is easily soluble in hot water or ethanol, soluble in acetone, slightly soluble in water.
melting point
The melting point of this product (general rule 0612) is 168~172 ℃.
identify
1. Add ferric chloride test solution to the aqueous solution of this product, and it will turn blue and purple.
2. Take about 0.1g of this product, add 5mL of dilute hydrochloric acid, heat it in a water bath for 40 minutes, cool it, take 0.5mL, add 5 drops of sodium nitrite test solution, shake it well, dilute it with 3mL of water, add alkalineβ-Tsai phenol test solution 2mL, shake, it will turn red.
3. The infrared absorption spectrum of this product should be consistent with the control spectrum (spectrum set 131 figure).
inspect
acidity
Take 0.10g of this product, add 10mL of water to dissolve it, and determine according to the law (general rule 0631). The pH value should be 5.5~6.5.
Clarity and color of ethanol solution
Take 1.0g of this product, add 10mL of ethanol to dissolve it, and the solution should be clear and colorless. If it appears turbid, it should not be thicker than No. 1 turbidity standard solution (General Rule 0902 Method 1), and if it appears color, it should not be deeper than No. 2 brown red or No. 2 orange red standard solution (General Rule 0901 Method 1).
chloride
Take 2.0g of this product, add 100mL of water, heat and dissolve it, cool it, filter it, take 25mL of filtrate, check it according to the law (general rule 0801), and it shall not be more concentrated (0.01%) than the control solution made of 5.0mL of standard sodium chloride solution.
sulfate
Take 25mL of the remaining filtrate under the item of chloride, and check according to the law (general rule 0802). Compared with the control solution made of 1.0mL of standard potassium sulfate solution, it should not be more concentrated (0.02%).
Related substances
It is determined according to the high performance liquid chromatography (general rule 0512), and is newly prepared for clinical use.
Solvent: methanol water (4:6).
Test solution: Take appropriate amount of this product, weigh it accurately, add solvent to dissolve it and dilute it quantitatively to prepare a solution containing about 20mg per 1mL.
Reference solution: Take an appropriate amount of paraaminophenol reference solution, weigh it precisely, add solvent to dissolve it and dilute it quantitatively to prepare a solution containing about 0.1mg per 1mL.
Reference solution: precisely measure 1mL of the reference solution and 1mL of the test solution, place them in the same 100mL volumetric flask, dilute them to the scale with solvent, and shake them up.
Chromatographic conditions: octyl silane bonded silica gel is used as the filler, phosphate buffer solution (8.95g of disodium hydrogen phosphate, 3.9g of sodium dihydrogen phosphate, add water to dissolve to 1000mL, add 12mL of 10% tetrabutylammonium hydroxide solution) - methanol (90:10) is used as the mobile phase, the detection wavelength is 245nm, the column temperature is 40 ° C, and the injection volume is 20μL。
System applicability requirements: the number of theoretical plates shall not be less than 2000 based on the peak of acetaminophen, and the separation between the peak of acetaminophen and the peak of acetaminophen shall meet the requirements.
Determination method: Precisely measure the test solution and the reference solution, respectively inject them into the liquid chromatograph, and record the retention time of the chromatogram to the main peak 4 times.
Limit: if there is a chromatographic peak in the chromatogram of the test solution that is consistent with the retention time of paracetamol, the peak area shall be calculated according to the external standard method. The paracetamol content shall not exceed 0.005%, and the peak area of other single impurities shall not be greater than 0.1 times (0.1%) of the peak area of paracetamol in the control solution,The sum of the peak areas of other impurities shall not be greater than 0.5 times (0.5%) of the peak area of acetaminophen in the reference solution.
P-Chlorophenylacetamide
It is determined according to the high performance liquid chromatography (general rule 0512), and is newly prepared for clinical use.
Solvent and test solution: see relevant substances.
Reference solutionμG and acetaminophen 20μG mixed solution.
Chromatographic conditions: octyl silane bonded silica gel is used as filler, phosphate buffer solution (8.95g of disodium hydrogen phosphate, 3.9g of sodium dihydrogen phosphate, add water to dissolve to 1000mL, add 12mL of 10% tetrabutylammonium hydroxide) - methanol (60:40) is used as mobile phase, detection wavelength is 245nm, column temperature is 40 ℃, and injection volume is 20μL。
System applicability requirements: the number of theoretical plates shall not be less than 2000 based on the peak of acetaminophen, and the separation degree between the peak of parachlorobenzamide and the peak of acetaminophen shall meet the requirements.
Determination method: Precisely measure the test solution and the reference solution, respectively inject them into the liquid chromatograph, and record the chromatogram.
Limit: calculated by peak area according to external standard method, the content of p-chlorophenylacetamide shall not exceed 0.005%.
Loss on drying
Take this product, dry it at 105 ℃ to constant weight, and the weight loss shall not exceed 0.5% (general rule 0831).
Ignition residue
Not more than 0.1% (general rule 0841).
heavy metal
Take 1.0g of this product, add 20mL of water, heat it in a water bath to dissolve, cool it, filter it, take 2mL of acetate buffer solution (pH 3.5) and appropriate amount of water to make 25mL of the filtrate, check according to the law (general rule 0821 method 1), and the content of heavy metals should not exceed 10% per million.
Assay
It is determined by ultraviolet visible spectrophotometry (general rule 0401).
Test solution
Take about 40mg of this product, precisely weigh it, put it into a 250mL measuring flask, add 50mL of 0.4% sodium hydroxide solution to dissolve it, dilute it with water to the scale, shake it up, precisely measure 5mL, put it into a 100mL measuring flask, add 10mL of 0.4% sodium hydroxide solution, dilute it with water to the scale, shake it up.
Assay
Take the test solution, measure the absorbance at the wavelength of 257nm, and press CeightHnineNOtwoAbsorption coefficient of（E1%1cm）Calculated for 715.
category
Antipyretic and analgesic, non steroidal anti-inflammatory drugs.
Storage
Sealed storage.
preparation
1. Acetaminophen Tablets.
2. Acetaminophen Chewable Tablets.
3. Acetaminophen effervescent tablets.
4. Acetaminophen injection.
5. Paracetamol suppository.
6. Acetaminophen Capsules.
7. Paracetamol granules.
8. Acetaminophen drops.
9. Acetaminophen gel.[7]
Related research
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The research team of Beijing University of Chemical Technology published a paper titled "Design and construction of an artificial path for biosynthesis of acetaminophen inEscherichia coli”By designing and constructing an artificial biosynthetic pathway, the team realized the production of paracetamol, a non natural product, by microorganisms for the first time.Paracetamol, also known as paracetamol, is one of the main drugs for analgesia and fever treatment.The team designed a new pathway for acetaminophen biosynthesis based on the principle of enzyme heterogeneity and substrate product similarity, and realized the biosynthesis of acetaminophen.By adopting the temperature response control system, the accumulation of by-products in the synthesis route was reduced, and the yield of acetaminophen was 120.03 mg/L.This study laid a foundation for the industrial green production of acetaminophen.[1-2]
security information
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Safety terminology
S26：In case of contact with eyes, rinse immediately with plenty of water and seek medical advice.
After eye contact, immediately flush with plenty of water and seek medical advice.
S36/37/39：Wear suitable protective clothing, gloves and eye/face protection.
Wear appropriate protective clothing, gloves and eye/face protection.
S61：Avoid release to the environment. Refer to special instructions/Safety data sheets.
Avoid releasing into the environment, refer to special instructions/safety receipt instructions.
Risk terminology
R22：Harmful if swallowed.
It is harmful if swallowed.
R36/37/38：Irritating to eyes, respiratory system and skin.
Irritating to eyes, respiratory system and skin.
R40：Possible risks of irreversible effects.
There may be risk of irreversible effects.
R52/53：Harmful to aquatic organisms, may cause long-term adverse effects in the aquatic environment.
It is harmful to aquatic organisms and may cause long-term adverse effects in the aquatic environment.
