Obeticholic acid and detection method for related substances in preparation of obeticholic acid

A technology of obeticholic acid and detection method, which is applied in the direction of measuring devices, instruments, scientific instruments, etc., can solve problems such as interference and inconsistent drugs, and achieve the effect of high separation, good reproducibility, and strong superiority

Inactive Publication Date: 2017-05-10
SHANDONG ACADEMY OF PHARMACEUTICAL SCIENCES
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] At present, there is no literature report on the analytical method of obeticholic acid in China, and there is no uniform drug standard for this drug. Therefore, in order to better control the quality of obeticholic acid products, it is necessary to establish a simple, reliable, stable and effective method. The method is used to detect the related substances of this product, and solve the interference of various known or unknown impurities introduced by the synthesis process or produced by degradation and preparation processing on the determination of product purity.

Method used

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  • Obeticholic acid and detection method for related substances in preparation of obeticholic acid
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  • Obeticholic acid and detection method for related substances in preparation of obeticholic acid

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Experimental program
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Effect test

Embodiment 1

[0026] 1. Chromatographic conditions and system suitability experiment:

[0027] 1.1 Selection of chromatographic conditions:

[0028] Instrument: Shimadzu: LC-20AT, SPD-M20A, SIL-20A, DGU-20A5, the optimum column temperature is 22°C, and the flow rate is 1.0ml / min. The liquid chromatography column uses octadecylsilane bonded silica gel as the filler (250mm×4.6mm, 5μm). Referring to the relevant literature and combined with the specific conditions of the experiment, methanol-water, acetonitrile-water, methanol-water-acetonitrile, and Methanol-water-glacial acetic acid, methanol-water-phosphate buffer and other conditions, the final determination of 0.01mol / L NaH 2 PO 4 Solution (pH3.8)-acetonitrile-methanol composition, the optimal ratio is: 25:35:40. The injection volume is 10 μl.

[0029] Under this chromatographic condition, the main peak of obeticholic acid had a moderate retention time and a good peak shape.

[0030] 1.2 Sensitivity determination

[0031] Take an ap...

Embodiment 2

[0042] Embodiment Two: Determination of Related Substances of Obeticholic Acid Tablets

[0043] Take 20 tablets of this product, accurately weigh, grind finely, and accurately measure an appropriate amount (approximately equivalent to 2 mg of obeticholic acid).

[0044] Add mobile phase to configure a solution containing 0.2 mg per 1 ml, filter, and take the filtrate as the test solution. Precisely measure an appropriate amount, add mobile phase to dilute to a solution containing about 2 μg per 1 ml, and use it as a control solution. Under the following selected chromatographic conditions:

[0045] Diode array detector (Shimadzu: LC-20AT, SPD-M20A, SIL-20A, DGU-20A5), octadecylsilane bonded silica gel as filler, 0.01mol / L NaH 2 PO 4 Solution (pH3.8)-acetonitrile-methanol composition, the optimal ratio is: 25:35:40, the column temperature is 22°C, and the flow rate is 1.0ml / min. The theoretical pedal is not less than 3000 based on the peak of obeticholic acid.

[0046] Mea...

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Abstract

The invention discloses an obeticholic acid and a detection method for related substances in a preparation of the obeticholic acid. The detection method includes the specific steps that the high performance liquid chromatography method is adopted, and a C18 column is adopted; a diode array detector is adopted, and the column temperature is 20 DEG C to 30 DEG C; a phosphate buffering liquid-acetonitrile-methyl alcohol solution serves as a moving phase for isocratic elution. By means of the detection method, the conditions of impurities and degradation products of the obeticholic acid can be rapidly and accurately detected, effective separation of the obeticholic acid and all known impurities can be achieved, the interference of all kinds of impurities generated in the synthesis and preparation processes of the obeticholic acid in the product purity is avoided, and the quality of raw material medicine and the quality of the preparation can be fully and reliably controlled. The detection method is easy and convenient to operate, high in sensitivity and good in separation degree, and an effectively analysis method is provided for controlling the quality of the product.

Description

[0001] The invention relates to a method for detecting related substances in obeticholic acid and its preparations, belonging to the field of drug analysis and detection. Background technique [0002] Obeticholic acid (OCA), the chemical structural formula is as follows: [0003] [0004] Chemical name: 6α-ethyl-3α, 7α-dihydroxy-5β-cholan-24-oic acid, which is a farnesoid X receptor agonist. In May 2014, the U.S. FDA granted Obeticholic Acid Fast Track Designation to Intercept Pharmaceuticals. Obeticholic acid indirectly inhibits the gene expression of cytochrome 7A1 (CYP7A1) by activating the farnesoid X receptor. Since CYP7A1 is the rate-limiting enzyme of bile acid biosynthesis, obeticholic acid can inhibit bile acid synthesis for the treatment of primary biliary cirrhosis and nonalcoholic fatty liver disease. [0005] In the past few years, experimental results have shown that obeticholic acid may introduce residual raw materials and other related substances during th...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): G01N30/02
CPCG01N30/02
Inventor 付丙月张宁段崇刚王帆任文杰刘宪华孔祥雨
Owner SHANDONG ACADEMY OF PHARMACEUTICAL SCIENCES
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