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Preparation method of dexamethasone sodium phosphate impurities I

A technology of dexamethasone sodium phosphate and impurities, which is applied in the field of preparation of pharmaceutical impurity standard products, and achieves the effects of simple processing steps, avoiding desalination operations, and high processing precision

Inactive Publication Date: 2017-04-19
天津阿尔塔科技有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The Chinese Pharmacopoeia requires that the dexamethasone sodium phosphate impurity I and other impurities in the dexamethasone sodium phosphate injection be controlled, but there is no corresponding analysis and detection reference substance on the market, so the development of the dexamethasone sodium phosphate impurity I standard substance The preparation process can achieve high yield and mass production, which has high application value and important social significance for detecting the quality of dexamethasone sodium phosphate injection

Method used

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  • Preparation method of dexamethasone sodium phosphate impurities I
  • Preparation method of dexamethasone sodium phosphate impurities I
  • Preparation method of dexamethasone sodium phosphate impurities I

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0026] The aqueous solution (900ml) of compound 1 (dexamethasone sodium phosphate, 90g) and sodium bisulfite (360g, molar ratio 1:20), adjust pH to 7 with the sodium hydroxide solution of 2mol / l, above-mentioned mixed solution is in Under stirring state, react at 60°C for 36h, and then cool the reacted mixed solution to 15°C.

[0027] The mixed solution obtained by the reaction is purified by reverse-phase preparative chromatography, and the purification conditions are: under neutral conditions, the chromatographic column specification (C18, 10um, ), mobile phase: methanol: water=20:80, flow rate: 80mL / min, obtain in the methanol-water solution containing dexamethasone sodium phosphate impurity I, then above-mentioned solution is concentrated under reduced pressure at 25 ℃ to remove methanol, then dry The water was removed, and then the obtained dexamethasone sodium phosphate impurity I was in P 2 o 5 It was further dried under the existing vacuum condition to obtain the ta...

Embodiment 2

[0029] Aqueous solution (150ml) of compound 1 (dexamethasone sodium phosphate, 10g) and sodium bisulfite (40g, molar ratio 1:20), adjust pH to 6.5-7 with 2mol / l sodium hydroxide solution, mix the above The solution was stirred at 60°C for 48h, and then the reacted mixed solution was cooled to 10°C.

[0030] Then by reverse-phase preparative chromatography purification, the purification conditions are: under neutral conditions, chromatographic column specifications (C18, 10um, ), mobile phase: methanol: water=20:80, flow rate: 80mL / min, in the methanol-water solution containing dexamethasone sodium phosphate impurity I, then the above solution was concentrated under reduced pressure at 25°C to remove methanol, then frozen Dried to remove water, then the obtained dexamethasone sodium phosphate impurity I was further vacuum-dried in the presence of phosphorus pentoxide to obtain the target compound dexamethasone sodium phosphate impurity I (3.5g), which was a white solid with a ...

Embodiment 3

[0032] Aqueous solution (50ml) of compound 1 (dexamethasone sodium phosphate, 3g) and sodium bisulfite (1g, molar ratio 1:1.66), adjust pH to 8-9 with 2mol / l sodium hydroxide solution, mix the above The solution was stirred at 60°C for 48h, and then the reacted mixed solution was cooled to 10°C.

[0033] Then by reverse-phase preparative chromatography purification, the purification conditions are: under neutral conditions, chromatographic column specifications (C18, 10um, ), mobile phase: methanol: water=20:80, flow rate: 10mL / min, in the methanol-water solution containing dexamethasone sodium phosphate impurity I, then the above solution was concentrated under reduced pressure at 25°C to remove methanol, then frozen Dried to remove water, then the obtained dexamethasone sodium phosphate impurity I was further vacuum-dried in the presence of phosphorus pentoxide to obtain the target compound dexamethasone sodium phosphate impurity I (0.38g), which was a white solid with a yi...

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Abstract

The invention provides a preparation method of dexamethasone sodium phosphate impurities I. The preparation method comprises the following steps that a mixture water solution of a compound 1 (dexamethasone sodium phosphate) and NaHSO3 is prepared according to the proportion of the mol ratio of 1:(1 to 100); the pH of the mixture water solution is regulated to 6 to 9 by a sodium hydroxide solution with the mass concentration being 0.1 to 5mol / l; the mixed solution is subjected to temperature rise to 40 to 80 DEG C under the stirring condition; the constant-temperature reaction is performed for 24 to 60h; then, the mixed solution after the reaction is cooled to 5 to 25 DEG C; the mixed solution after the reaction is treated by purification and drying post-treatment processes; and obtained white solids are target compounds of dexamethasone sodium phosphate impurities I. Compared with the prior art, the preparation method of the dexamethasone sodium phosphate impurities I can be used for preparing a great number of standard products of dexamethasone sodium phosphate impurities I; the yield reaches 33 percent or higher; the post-treatment steps are simple; and the treatment precision is high.

Description

technical field [0001] The invention belongs to the field of preparation of pharmaceutical impurity standard products, in particular to a preparation method of dexamethasone sodium phosphate impurity I. Background technique [0002] The structural formula of dexamethasone sodium phosphate (DSP) is shown in figure 1 , chemical name 16a-methyl-11β,17a,21-trihydroxy-9a-fluoropregna-1,4-diene-3,20-diketone-21-phosphate disodium salt, belongs to adrenocortical hormones Drugs, clinically used in the treatment of various diseases such as autoimmune diseases, allergies, inflammation, asthma and dermatology. Dexamethasone sodium phosphate injection is a sterilized aqueous solution of dexamethasone sodium phosphate. In addition to the solvent, the injection can be added with appropriate excipients according to the physical and chemical properties of the drug, such as pH regulators, co-solvents, antioxidants, and antibacterial agents. Wait. Excipients for injection must comply with ...

Claims

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Application Information

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IPC IPC(8): C07J51/00
CPCC07J51/00
Inventor 张磊
Owner 天津阿尔塔科技有限公司