2 Pharmacopoeia standard methylthioimidazole 2. 1 product name 2. 1. 1 Chinese name methylthioimidazole
2. 1.2 Chinese Pinyin A Qiu Mi Zuo
2. 1.3 English name methimazole
2.2 structural formula
2.3 molecular formula and molecular weight C4H6N2S? 1 14. 16
2.4 Source (name) and content (potency) This product is 1 methylimidazole 2 mercaptan. The content of C4H6N2S shall be no less than 98.5% in terms of dry products.
2.5 Properties This product is white to yellowish crystalline powder; It has a slight smell.
This product is soluble in water, ethanol or chloroform, and slightly soluble in ether.
2.5. 1 melting point the melting point of this product (appendix ⅵ C of Pharmacopoeia II, 20 10) is 144 ~ 147℃.
2.6 Identification (1) Take about 2mg of this product, add 1ml water to dissolve it, add 1ml sodium hydroxide test solution, shake well, and drop 3 drops of sodium nitrosferricyanide test solution, which is yellow; Turn yellow-green or green after a few minutes; Add acetic acid 1 ml, blue.
(2) The infrared absorption spectrum of this product should be consistent with the control spectrum (drug infrared spectrum acquisition chart 1 17).
2.7 Check the acidity of 2.7. 1 Take 0.50g of this product, add 25ml of water to dissolve it, and measure it according to law (Appendix VI H of Pharmacopoeia Part II, 20 10), and the pH value should be 5.0 ~ 7.0.
2.7.2 Related substances Take this product, add ethyl acetate to dissolve and dilute it, and make a solution containing 65438±00mg per 65438±0ml as the test solution; Accurately measure an appropriate amount, dilute it with ethyl acetate, and prepare solutions containing 200μg 1ml, 100μg, 50μg 10μg, and 1 0μ g as control solutions (1), (2), (3) and (4) respectively. According to the test of thin-layer chromatography (appendix ⅴ b of Pharmacopoeia Part II, 20 10), 20μl of the above five solutions were absorbed and spotted on the same silica gel G thin-layer plate, with toluene-isopropanol-concentrated ammonia solution (70: 29: 1) as the developing agent, developed, dried, and sprayed with potassium iodoplatinate solution (take chloroplatinic acid 0. If there are impurity spots in the test solution, compared with the main spots in the control solutions (1), (2), (3) and (4), the total amount of impurities shall not exceed 2.0%.
2.7.3 Residual solvent 2.7.3. 1 benzene Take about 1.0g of this product, weigh it accurately, put it in an empty bottle, add 5ml of water accurately to dissolve it, and seal it as a test solution; Accurately weigh a proper amount of benzene, dilute it with water to make a solution containing about 0.4ug per 1ml, accurately measure 5ml, and put it in an empty bottle to seal it as a control solution. According to the residual solvent determination method (the second method in Appendix VIII P of Pharmacopoeia Part II, 20 10), 6% cyanopropyl phenyl 94% dimethyl polysiloxane (or similar polarity) was used as the stationary liquid; The initial temperature is 70℃, maintained for 8 minutes, and the temperature is raised to 200℃ at the rate of 30℃ per minute, and maintained for 3 minutes; The temperature of the sample inlet is 220℃; The detector temperature is 250℃; The equilibrium temperature of the top empty bottle is 85℃ and the equilibrium time is 30 minutes. Take the test solution and the reference solution for headspace sampling, record the chromatogram, and calculate the peak area according to the external standard method, which should comply with the regulations. [ 1]
2.7.4 loss on drying takes this product and dries it to constant weight at 105℃, and the weight loss shall not exceed 0.5% (Appendix VIII L of Pharmacopoeia II, 20 10).
2.7.5 Take this product 1.0g as residue on ignition, and check it according to law (Appendix VIII N of Pharmacopoeia II, 20 10), and the residue shall not exceed 0. 1%.
2.7.6 Take the residue left under the heavy metal residue on ignition and check it according to law (the second method in Appendix VIII H of Pharmacopoeia 20 10), and the content of heavy metals shall not exceed 10 parts per million.
2.8 content determination: take about 0. 1g of this product, weigh it accurately, add 35ml of water to dissolve it, first add 4ml of sodium hydroxide titration solution (0.1mol/l) from the burette, shake it evenly, then drop 1.5ml of silver nitrate solution, shake it evenly, and then add musk bromide. Every 1ml sodium hydroxide titration solution (0. 1mol/L) is equivalent to11.42mg c4h6n2s.
Class 2.9 Antithyroid drugs.
2. 10 storage is sealed.
2. 1 1 Preparation of methylthioimidazole tablets
2. 12 Edition People's Republic of China (PRC) Pharmacopoeia 20 10 Edition
3 instructions for methylthioimidazole 3. 1 drug name methylthioimidazole
3.2 English name Thiamazole
3.3 Another name for methylthioimidazole, tabazole; Thiothiazole; Methimazole; Mecazole; Methimazole; Tabazole; Tiazol
3.4 classification of endocrine system drugs > drugs for thyroid diseases
3.5 dosage form tablets: 5mg each.
3.6 The pharmacological mechanism of methylthioimidazole is the same as that of propylthiouracil, but its effect is stronger than that of propylthiouracil (the dose is110, but its effect is 20 times), and it takes effect quickly, metabolizes slowly and lasts for a long time.
3.7 Pharmacokinetics of methylthioimidazole can be rapidly absorbed from gastrointestinal tract after oral administration. The peak time of plasma concentration is1~ 2 hours, and it is not bound to plasma protein, and the plasma half-life is 3 ~ 6h hours. Drugs in the body are mainly concentrated in the thyroid gland, so its action time is longer than the half-life predicted. The elimination of drugs in thyroid gland is slower than that in serum, and it is feasible to administer 1 time every day. Drugs may be metabolized in the liver, and most prototypes and metabolites are excreted in urine, of which prototype drugs account for 12% of the dose. It penetrates the placenta more easily than propylthiouracil and is secreted into breast milk. For patients with hepatic and renal insufficiency, the elimination will be slow.
3.8 Indications of methylthioimidazole are used for hyperthyroidism, preoperative preparation for hyperthyroidism or preparation for radioactive iodine therapy, thyroid crisis, etc.
3.9 Contraindications of methylthioimidazole Patients with nodular hyperthyroidism and thyroid cancer are prohibited. It is forbidden for those who are allergic to methylthioimidazole.
3. 10 Precautions 1. Pregnant women and lactating women should use it with caution.
2. preoperative preparation should increase the dose of iodine.
3. Patients taking methylthioimidazole should be closely monitored. Once there is fever, runny nose, leukopenia, rash, exfoliative dermatitis, allergies and other adverse reactions. They should stop taking medicine immediately and check their blood routine regularly.
4. Excessive application will cause hypothyroidism, so stop taking the medicine immediately.
5. Occasionally bleeding or prothrombin deficiency can be given vitamin K preparation.
3. The adverse reactions of11methylthioimidazole were seen in propylthiouracil, and the incidence of adverse reactions was slightly lower.
3. Usage and dosage of12 methylthioimidazole The initial dosage is 15 ~ 60mg/min 1 ~ 3 times a day. After about 1 ~ 2 months, thyroid function returned to normal, and the maintenance dose was changed to 5 ~ 30 mg per day. Treatment needs to last for 6 ~ 24 months, usually 12 ~ 24 months. The initial dose for children is 400μg/kg, and the maintenance dose is halved.
3. 13 drug interaction propylthiouracil
3. 14 Expert opinion