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Oxytetracycline hydrochloride

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Oxytetracycline hydrochloride is an organic compound with chemical formula C twenty-two H twenty-five ClN two O nine It is a tetracycline antibiotic.

Chinese name: Oxytetracycline hydrochloride
Foreign name: Oxytetracycline Hydrochloride
chemical formula: C twenty-two H twenty-five ClN two O nine
molecular weight: four hundred and ninety-six point eight nine
CAS login number: 2058-46-0
EINECS login number: 218-161-2
Melting point: 180 ℃

Boiling point: 839.6 ℃
Water solubility: soluble
Density: 1.71 g/cm³
Appearance: Yellow crystalline powder
Flash point: 461.6 ℃
Security description: S26；S36/37/39
Hazard symbol: Xn
Hazard description: R36；R63

catalog

▪ Dosage and usage
▪ indication
▪ Adverse reactions
▪ Drug interaction
▪ Drugs for pregnant and lactating women
▪ Children's medication

Compound Introduction

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essential information

Chemical formula: C twenty-two H twenty-five ClN two O nine

Molecular weight: 496.89

CAS No.: 2058-46-0

EINECS No.: 218-161-2

Physical and chemical properties

Density: 1.71g/cm three

Melting point: 180 ° C

Boiling point: 839.6 ° C

Flash point: 461.6 ° C

Steam pressure: 2.17E-30mmHg at 25 ° C

Appearance: white crystalline powder

Solubility: soluble in water^[1]

Calculate chemical data

Reference value for drainage parameter calculation (XlogP): None

Number of hydrogen bond donors: 8

Number of hydrogen bond receptors: 11

Number of rotatable chemical bonds: 1

Number of tautomers: 168

Topological molecule polar surface area (TPSA): 202

Number of heavy atoms: 34

Surface charge: 0

Complexity: 1000

Number of isotope atoms: 0

Determine the number of atomic structure centers: 6

Number of uncertain atomic structure centers: 0

Determine the number of chemical bond stereocenters: 1

Number of uncertain chemical bond structure centers: 0

Number of covalent bond units: 2^[1]

Brief Introduction to Drugs

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pharmacological action

It is a broad-spectrum antibiotic. Its antibacterial spectrum, antibacterial principle and application are basically the same as tetracycline. Many Rickettsia, Mycoplasma, Chlamydia, Spirochetes, Amoeba and some Plasmodium are also sensitive to this product. Enterococcus is resistant to it. Others, such as Actinomyces, Bacillus anthracis, Listeria monocytogenes, Clostridium, Nocardia, Vibrio, Brucella, Campylobacter, Yersinia, are sensitive to this product.

This product has certain antibacterial activity against Neisseria gonorrhoeae and meningococcus, but penicillin resistant Neisseria gonorrhoeae is also resistant to oxytetracycline. Over the years, due to the extensive application of tetracyclines, the common clinical pathogens are seriously resistant to oxytetracycline, including gram-positive bacteria such as staphylococcus and most gram-negative bacteria. Cross resistance exists among different varieties of tetracycline antibiotics. The mechanism of action of this product is that the drug can specifically bind to the A position of bacterial ribosome 30S subunit, inhibit the growth of peptide chain and affect the synthesis of bacterial protein. This product is slightly more effective than tetracycline in treating intestinal infections, including amebic dysentery. It has close cross resistance to tetracycline.

Dosage and usage

Oral: 0.5g once, four times a day. Children over 8 years old take 30~40mg/kg body weight every day, divided into 3~4 times.

indication

1. This product can be used as a selective drug for the following diseases:

(1) Rickettsia diseases include epidemic typhus, endemic typhus, Rocky Mountain fever, scrub typhus and Q fever.

(2) Mycoplasma infection.

(3) Chlamydia infections include psittacosis, venereal diseases, lymphosarcoidosis, nonspecific urethritis, salpingitis, cervicitis and trachoma.

(4) Regression fever.

(5) Brucellosis.

(6) Cholera.

(7) Rabbit fever.

(8) Plague.

(9) Chancre.

Treatment of brucellosis and plague needs to be combined with aminoglycosides.

2. Due to the serious drug resistance of common pathogenic bacteria to this product, only when the pathogenic bacteria are sensitive to this product can they be used as drugs of choice: Gram negative bacterial infections such as Escherichia coli, Enterobacter aerogenes, Acinetobacter Lofiti, Shigella, Haemophilus influenzae (only for respiratory tract infections) and Klebsiella (only for respiratory tract and urinary tract infections) that are sensitive to this product. This product is not suitable for any type of staphylococcal or hemolytic streptococcal infection.

3. This product can be used in patients with penicillin allergic tetanus, gas gangrene, yaws, syphilis, gonorrhea, leptospirosis, and actinomycetes, Listeria infection.

4. It can be used as an auxiliary treatment for patients with acute intestinal amebiasis and moderate to severe acne.

Adverse reactions

1. Digestive system: gastrointestinal symptoms such as nausea, vomiting, epigastric discomfort, abdominal distention, diarrhea, and occasional reports of pancreatitis, esophagitis, and esophageal ulcer, mostly occur in patients who lie in bed immediately after taking medicine.

2. Hepatotoxicity: It is usually fatty liver degeneration. Pregnant women and patients with original renal function damage are prone to hepatotoxicity, but hepatotoxicity can also occur in patients without the above conditions.

3. Allergic reaction: most of them are maculopapules and erythema. In addition, urticaria, angioneurotic edema, anaphylactoid purpura, pericarditis and systemic lupus erythematosus are aggravated. Exfoliative dermatitis is not common. Allergic shock and asthma occasionally occur. Some patients with tetracycline have photosensitivity when exposed to the sun. Therefore, patients should be advised not to be directly exposed to the sun or ultraviolet rays. Once there is erythema on the skin, the drug should be stopped immediately.

4. Blood system: occasionally cause hemolytic anemia, thrombocytopenia, neutropenia and eosinophilia.

5. Central nervous system: It can occasionally cause benign intracranial hypertension, which can be manifested as headache, vomiting, papilloedema, etc.

6. Nephrotoxicity: patients with significant renal function damage may have increased azotemia, hyperphosphatemia and acidosis.

7. Double infection: Long term use of this product can cause digestive tract, respiratory tract and urinary tract infections of drug-resistant Staphylococcus aureus, gram-negative bacteria and fungi, and even septicemia in severe cases.

8. This product can be deposited in teeth and bones, causing varying degrees of discoloration and yellowing of teeth, enamel dysplasia and caries, and bone dysplasia.

9. The application of this product can reduce the normal flora in the human body, resulting in vitamin B deficiency, fungal reproduction, dry mouth, sore throat, angular stomatitis and glossitis.

Drug interaction

1. When used together with antacids such as sodium bicarbonate, the absorption and activity of this product will be reduced due to the increase of pH value in the stomach, so antacids should not be taken within 1-3 hours after taking this product.

2. Drugs containing calcium, magnesium, iron and other metal ions can form insoluble complexes with the product, reducing the absorption of the product.

3. When used together with the general anesthetic methoxyflurane, it can enhance its nephrotoxicity.

4. When used with strong diuretics such as furosemide, renal function damage can be aggravated.

5. When used together with other hepatotoxic drugs (such as anti-tumor chemotherapy drugs), liver damage can be aggravated.

6. The hypolipidemic drug colesenemide or coletipol can affect the absorption of this product, and must be taken separately at intervals of several hours.

7. This product can reduce the effect of contraceptives and increase the possibility of extramenstrual bleeding.

8. This product can inhibit the activity of plasma prothrombin, so patients receiving anticoagulant treatment need to adjust the dosage of anticoagulant.

Drugs for pregnant and lactating women

This product can enter the fetus through the placental barrier and deposit in the calcareous area of teeth and bone, causing discoloration of fetal teeth, poor regeneration of tooth enamel and inhibiting the growth of fetal bone. In addition, this kind of drug has teratogenic effect in animal experiments, so it is not suitable for pregnant women to use this product. This product can be secreted from milk, and the concentration in milk is high, which may potentially cause serious adverse reactions to infants. Breastfeeding should be suspended when women use it during lactation.

Children's medication

This product can form stable calcium compounds in any bone tissue, resulting in permanent teeth yellowing, tooth enamel dysplasia and bone growth inhibition. Therefore, this product is not suitable for children under 8 years old.

Medication for elderly patients

Elderly patients are often accompanied by renal dysfunction, and the application of this product is likely to cause hepatotoxicity, so the dosage of this product should be adjusted according to the degree of renal dysfunction in elderly patients.

Pharmacopoeia information

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source

This product is 6-methyl-4 - (dimethylamino) - 3,5,6,10,12,12 α -Hexahydroxy-1,11-dioxo-1,4,4 α ,5,5 α ,6,11,12 α -Octahydro-2-oxotetrabenzamide hydrochloride, calculated as anhydrous, contains oxytetracycline (C twenty-two H twenty-four N two O nine ）Not less than 88.0%.

character

This product is a yellow crystalline powder, odorless, hygroscopic, darkening in sunlight, and easy to be damaged and invalid in alkaline solution.

This product is easily soluble in water, slightly soluble in methanol or ethanol, and insoluble in ether.

Specific curl

Take this product, weigh it precisely, add hydrochloric acid solution (9 → 1000) to dissolve it and dilute it quantitatively to make a solution containing about 10mg per 1mL. Determine according to the law (general rule 0621), and the specific rotation is - 188 ° to - 200 °.

identify

1. Take about 0.5mg of this product, add 2mL of sulfuric acid, which will show deep vermilion, and then add 1mL of water, the solution will turn yellow.

2. Test according to thin layer chromatography (general rule 0502).

Test solution: take this product, add methanol to dissolve and dilute it to make a solution containing about 1mg per 1mL.

Reference solution: Take the control substance of terramycin, add methanol to dissolve and dilute it to make a solution containing about 1mg per 1mL.

System suitability solution: Take oxytetracycline and tetracycline hydrochloride reference substances, add methanol to dissolve and dilute them into a mixed solution containing about 1mg each in 1mL.

Chromatographic conditions: silica gel G (H) F two hundred and fifty-four Thin layer plate, with water methanol dichloromethane (6:35:59) as developing agent.

Determination method: Pipet 1 µ L of each of the three solutions mentioned above, dot them on the same thin plate, develop them, dry them, and inspect them under ultraviolet light (365nm).

System suitability requirements: the system suitability solution should show two completely separated spots.

Result judgment: The position and fluorescence of the main spot of the test solution should be the same as that of the control solution.

3. In the chromatogram recorded under the content determination item, the retention time of the main peak of the test solution should be consistent with the retention time of the main peak of the reference solution.

4. The aqueous solution of this product shows the reaction of chloride identification 1 (general rule 0301).

Either of the above 2 and 3 can be selected.

inspect

acidity

Take this product, add water to make a solution containing 10mg per 1mL, and determine according to the law (general rule 0631), the pH value should be 2.3~2.9.

Related substances

Determine according to the high performance liquid chromatography (general rule 0512).

Test solution: take a proper amount of this product, add 0.01mol/L hydrochloric acid solution to dissolve and dilute it to make a solution containing about 0.5mg per 1mL.

Reference solution: precisely measure 2mL of the test solution, place it in a 100mL measuring flask, dilute it with 0.01mol/L hydrochloric acid solution to the scale, and shake it up.

System suitability solution: take an appropriate amount of 4-epitetracycline reference substance, add 0.01mol/L hydrochloric acid solution to dissolve and dilute it into a solution containing about 0.5mg per 1mL, take an appropriate amount of terramycin reference substance (containing about 3% 2-acetyl-2-deamidoxytetracycline), add a small amount of 0.1mol/L hydrochloric acid solution to dissolve it, dilute it with water to make a solution containing about 0.5mg per 1mL of terramycin, take the above two solutions (1:24) Mix to prepare a mixed solution containing about 20 µ g of 4-epitetracycline and 480 µ g of oxytetracycline (about 14.5 µ g of 2-acetyl-2-deamidoxytetracycline) per 1mL.

Sensitivity solution: precisely measure 2mL of reference solution, place it in a 100mL measuring flask, dilute it to the scale with 0.01mol/L hydrochloric acid solution, and shake it up.

Chromatographic conditions: octadecyl silane bonded silica gel is used as the filler, ammonium acetate solution [0.25mol/L ammonium acetate solution -0.05mol/L ethylene diamine tetraacetic acid disodium solution triethylamine (100:10:1) is used, and acetic acid is used to adjust the pH value to 7.5] - acetonitrile (88:12) as the mobile phase, the detection wavelength is 280nm, and the injection volume is 10 µ L.

Requirements for system applicability: in the chromatogram of system applicability solution, the peak sequence is: 4-epitetracycline peak (relative retention time with oxytetracycline peak is about 0.9), oxytetracycline peak, 2-acetyl-2-deamidothoxycycline peak (relative retention time with oxytetracycline peak is about 1.1). The retention time of oxytetracycline peak is about 12 minutes, the resolution between 4-epitetracycline peak and oxytetracycline peak should be greater than 2.0, and the resolution between oxytetracycline peak and 2-acetyl-2-deamidoxytetracycline peak should be greater than 2.5. In the chromatogram of sensitive solution, the signal to noise ratio of the peak height of the main component should be greater than 10.

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 component peak 4 times.

Limit: if there is an impurity peak in the chromatogram of the test solution, the peak area of 2-acetyl-2-deamidoxytetracycline shall not be greater than 1.75 times (3.5%) of the main peak area of the reference solution, and the sum of the peak areas of other impurities shall not be greater than the main peak area of the reference solution (2.0%), and the peaks smaller than the main peak area of the sensitivity solution shall be ignored.

Impurity absorbance

Take this product, add 0.1mol/L hydrochloric acid methanol solution (1 → 100) to dissolve and quantitatively dilute it to make a solution containing 2.0mg per 1mL. According to the ultraviolet visible spectrophotometry (general rule 0401), within one hour, measure at the wavelength of 430nm, and the absorbance should not exceed 0.50. Take this product, add the above hydrochloric acid methanol solution to dissolve and quantitatively dilute it to make a solution containing 10mg per 1mL, The absorbance shall not exceed 0.20 when measured at the wavelength of 490nm.

water content

Take this product and measure it according to the moisture determination method (General Rule 0832, Method 1). The moisture content should not exceed 2.0%.

Assay

Determine according to the method of high performance liquid chromatography (general rule 0512).

Test solution

Take an appropriate amount of this product (about 25mg of oxytetracycline), weigh it precisely, put it into a 50mL measuring bottle, add 0.01mol/L hydrochloric acid solution to dissolve it and dilute it to the scale, shake it up, weigh 5mL precisely, put it into a 25mL measuring bottle, dilute it to the scale with 0.01mol/L hydrochloric acid solution, shake it up.

Reference solution

Take the control sample of terramycin, weigh it precisely, add 0.01mol/L hydrochloric acid solution to dissolve it and dilute it quantitatively to prepare a solution containing about 0.1mg per 1mL.

System suitability Solution and chromatographic conditions

See related substances.

System suitability requirements

In addition to sensitivity requirements, see related substances.

Assay

Accurately measure the test solution and the reference solution, respectively inject them into the liquid chromatograph, and record the chromatogram. Calculate C in the test sample by peak area according to external standard method twenty-two H twenty-four N two O nine Content of.