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High performance liquid chromatography method of macitentan related substances

A technology of high performance liquid chromatography and analysis methods, applied in the direction of analysis materials, material separation, measurement devices, etc., can solve the problem that there are no relevant literature reports on the analysis methods of macitentan raw materials and their preparations, and achieve strong specificity Effect

Active Publication Date: 2016-03-09
合肥启旸生物科技有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] At present, there is no relevant literature report on the analysis method of macitentan raw material and its preparation

Method used

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  • High performance liquid chromatography method of macitentan related substances
  • High performance liquid chromatography method of macitentan related substances
  • High performance liquid chromatography method of macitentan related substances

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0041] Detection equipment and chromatographic conditions:

[0042] High performance liquid chromatography: LC-10AD pump, SPD-M10A detector

[0043] Chromatographic column: AgilentC18 (250×4.6mm, 5μm); mobile phase A: acetonitrile-water-formic acid solution with a volume ratio of 49:51:0.1; mobile phase B: acetonitrile-water-formic acid solution with a volume ratio of 85:15:0.1 Formic acid solution; detection wavelength: 260nm; flow rate: 1.0ml / min; injection volume: 20μl.

[0044] Experimental steps:

[0045] (1) Sample preparation:

[0046] Take an appropriate amount of macitentan and known impurities A-R, and use ammonium bicarbonate buffer solution with a volume ratio of 1:4 (take 1.58g of ammonium bicarbonate, add 1000ml of water to dissolve, adjust the pH value to 9.0 with ammonia water)-acetonitrile solution for ultrasonication Dissolve and dilute to make a solution containing about 1 mg / ml of macitentan and about 1 μg / ml of impurities A-R, as a sample solution;

[00...

Embodiment 2

[0052] Detection equipment and chromatographic conditions:

[0053] High performance liquid chromatography: LC-10AD pump, SPD-M10A detector

[0054] Chromatographic column: Agilent C18 (250×4.6 mm, 5 μm); mobile phase A: same as Example 1, mobile phase B: same as Example 1; flow rate: 1.0 ml / min; detection wavelength: 260 nm; injection volume: 20 μl.

[0055] (1) Sample preparation:

[0056] Acid destruction: Take macitentan tablets, grind them finely, take an appropriate amount of fine powder (approximately equivalent to 50mg containing macitentan), take 50mg of macitentan raw materials, put them in a 50ml measuring bottle, add 5ml of 1mol / L hydrochloric acid solution , placed in a water bath at 80°C for 1 hour, cooled rapidly, added 5ml of 1mol / L sodium hydroxide solution to neutralize, and used ammonium bicarbonate buffer solution with a volume ratio of 1:4 (take 1.58g of ammonium bicarbonate, add 1000ml of water to dissolve, and use ammonia water Adjust the pH value to 9...

Embodiment 3

[0066] Detection equipment and chromatographic conditions:

[0067] High performance liquid chromatography: SSISeries1500 pump, Series1500PDA detector

[0068] Chromatographic column: Agilent C18 (250×4.6 mm, 5 μm); mobile phase A: same as Example 1, mobile phase B: same as Example 1; flow rate: 1.0 ml / min; detection wavelength: 260 nm; injection volume: 20 μl.

[0069] Experimental steps:

[0070] (1) Sample preparation: take an appropriate amount of macitentan, and use ammonium bicarbonate buffer solution with a volume ratio of 1:4 (take 1.58g of ammonium bicarbonate, add 1000ml of water to dissolve, adjust the pH value to 9.0 with ammonia water)-acetonitrile solution for ultrasound Dissolve and dilute to make a solution containing macitentan 1 mg / ml as the sample solution.

[0071] (2) Gradient elution program setting:

[0072] time (minutes)

Mobile phase A(%)

Mobile phase B(%)

0

100

0

10

100

0

35

0

100

...

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Abstract

The invention discloses a high performance liquid chromatography method of macitentan related substances. The method adopts a reversed phase chromatographic column and an ultraviolet detector, and adopts acetonitrile-water-formic acid as a mobile phase to carry out gradient elution. The method can be used to simultaneously analyze all known impurities in a macitentan raw material and preparations thereof, and also allows the content of the known impurities to be effectively controlled through a correction factor-containing main component self-contrasted technology, the resolution among all impurity peaks and the resolution between a main peak and an adjacent impurity peak are respectively greater than 1.5, and the peak purities of the main peak and all the impurity peaks are 1.0. The method is a simple and reliable analysis method for quality control of the macitentan raw material and the preparations thereof.

Description

1. Technical field [0001] The invention relates to a method for analyzing the purity of chemical drugs, in particular to a method for analyzing macitentan-related substances by high performance liquid chromatography. 2. Background technology [0002] Macitentan (Macitentan), chemical name N-[5-(4-bromophenyl)-6-[2-[(5-bromo-2-pyrimidinyl)oxy]ethoxy]-4-pyrimidine Base]-N'-propylsulfonamide, the chemical structural formula is the following formula (I): [0003] [0004] Macitentan is a bidirectional endothelin receptor antagonist developed by Actelion Pharmaceuticals Inc. in Switzerland. On October 18, 2013, it was approved by the US FDA for the treatment of pulmonary arterial hypertension (PAH) to delay the progression of the disease. [0005] There are many impurities in macitentan. From a structural point of view, there are two active equivalent reaction sites in the 5-(4-bromophenyl)-4,6-disubstituted pyrimidine core and the diethoxy structure (chloro atom, hydroxyl)...

Claims

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Application Information

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IPC IPC(8): G01N30/88G01N30/34G01N30/89
CPCG01N30/34G01N30/88G01N30/89G01N2030/027G01N2030/8872
Inventor 吴标李晓梅王娟施伶俐
Owner 合肥启旸生物科技有限公司
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