Impurity of ciclesonide and preparation method thereof

A technology of ciclesonide and cycloalkyl, which is applied in the field of ciclesonide impurities and its preparation, and can solve problems such as toxicity and affecting the curative effect of ciclesonide

Inactive Publication Date: 2013-04-03
CHONGQING PHARMA RES INST
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

For example, during synthesis or storage, impurities are often formed, including degradants or by-products of manufacture, which may thereby affect the efficacy of ciclesonide and / or may be toxic in the presence of sufficiently high amounts

Method used

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  • Impurity of ciclesonide and preparation method thereof
  • Impurity of ciclesonide and preparation method thereof
  • Impurity of ciclesonide and preparation method thereof

Examples

Experimental program
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Effect test

preparation example Construction

[0080] The preparation of ciclesonide (compound III) is, for example, according to the method described in Chinese patent CN1626546, which is fully incorporated by reference herein.

[0081] The instruments used for mass spectrometry were Agilent 1200 high performance liquid chromatography system and Agilent G6410A tandem triple quadrupole mass spectrometer. The ion source was electrospray ion source in positive ion mode. Split the HPLC eluate, allowing approximately 1 μg / ml into the ion source of the mass spectrometer.

[0082] The NMR analysis of formula Ⅱ compound is in CDCl 3 The instrument used was a Bruker Avance500 nuclear magnetic resonance spectrometer. TMS is used as a proton resonance (δ 1 H 0.00) and solvent internal reference, CDCl 3 As the carbon resonance internal standard (δ 1 C 77.00).

[0083] The following abbreviations are used and have the following meanings:

[0084] abbreviation Meaning δ chemical shift CDCl 3 deutera...

Embodiment 1

[0086] Embodiment 1: the HPLC analysis method of ciclesonide

[0087] Take an appropriate amount of this product, add methanol to dissolve, dilute with methanol to make a solution containing about 0.4mg per 1ml, as the test solution, and measure according to high performance liquid chromatography (Chinese Pharmacopoeia 2010 edition two appendix VD). Octadecylsilane bonded silica gel was used as filler, acetonitrile-water (90:10) was used as mobile phase, and the detection wavelength was 242nm. The number of theoretical plates should not be less than 5000 based on ciclesonide. Precisely measure 20 μl of the test solution, inject it into a liquid chromatograph, record the chromatogram to 6 times the retention time of the main peak, and calculate the purity of ciclesonide with the area normalization method. If necessary, the system peak area or solvent peak area can be deducted from the blank control.

Embodiment 2

[0088] Embodiment 2: the preparation of formula II compound

[0089] Dissolve 5 g of ciclesonide (compound of formula III) in 200 ml of methanol, place it under a 254 nm ultraviolet lamp, and track the reaction progress with HPLC until the basic reaction of the raw materials is complete and the solution turns pale yellow. After the reaction solution was concentrated under reduced pressure, it was diluted with acetonitrile and separated by preparative chromatography (chromatographic column: Agilent ZORBAX SB-C 18 21.2×250mm), mobile phase: acetonitrile:water=80:20, flow rate 10ml / min, collect target components, concentrate under reduced pressure to obtain target ciclesonide photodegradation product (compound of formula II). HPLC purity was 99.0%.

[0090] M+H in mass spectrum [ESI-MS, m / z] + Peak is 541.

[0091] 13 C NMR (500MHz, CDCl 3 ) δ (ppm): 207.2, 203.5, 176.7, 165.8, 132.0, 107.4, 97.6, 81.8, 67.9, 67.2, 54.6, 54.0, 49.3, 46.2, 40.8, 40.3, 39.1, 38.6, 33.8,...

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Abstract

The invention relates to a impurity compound ((11beta,16alpha)-16,17-[[(R)-cyclohexyl methylene]bis(oxy)]-11-hydroxy-21-(2-methyl-1-carbonyl propoxy)-1,5-cyclopregnane-3-ene-2,20-dione) of glucocorticoids drug ciclesonide, a preparation method thereof, and an application of the impurity compound as a reference in quality control of the ciclesonide.

Description

technical field [0001] The invention belongs to the field of chemical and pharmaceutical analysis, and in particular relates to an impurity compound of ciclesonide and a preparation method thereof, and the impurity (11β,16α)-16,17-[[(R)-cyclohexylmethylene ]bis(oxy)]-11-hydroxy-21-(2-methyl-1-carbonylpropoxy)-1,5-cyclopregn-3-ene-2,20-dione as ciclesonide Quality control refers to the use of the standard and the test method of ciclesonide and its impurities. Background technique [0002] Ciclesonide (Ciclesonide) is a new generation of adrenal corticosteroid drugs. It has highly effective local anti-inflammatory effects, can enhance the stability of endothelial cells and smooth muscle nuclei-lysosomal membranes, inhibit immune reactions, reduce antibody synthesis, and make histamine Reduce the release and activity of allergic reaction mediators, reduce the enzymatic process stimulated by the combination of antigen and antibody, inhibit the synthesis and release of bronchoco...

Claims

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Application Information

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IPC IPC(8): C07J71/00G01N30/02
Inventor 何伟万娟张伟罗杰张道林叶文润付晓泰蔡中文
Owner CHONGQING PHARMA RES INST
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