Method for measuring related substances in Riociguat raw material agents through HPLC separation

A technology related to substances and raw materials, applied in the field of high-performance liquid chromatography analysis, which can solve problems such as analytical method defects, pH sensitivity, and shortened service life of chromatographic columns

Active Publication Date: 2017-08-25
韩庆亮
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, this method uses anion-pairing reagents as a buffer solution. The concentration of ion-pairing reagents has a direct impact on the retention time of the sample, and the ion-pairing reagents are sensitive to pH, which directly affects the reproducibility of samples.
In addition, the ion-pairing reagent needs to balance the system for a long time, and it is difficult to wash off, which will greatly shorten the service life of the chromatographic column
[0005] In the existing technology, the analytical method suitable for the analysis and detection of related substances of riociguat API has serious defects

Method used

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  • Method for measuring related substances in Riociguat raw material agents through HPLC separation
  • Method for measuring related substances in Riociguat raw material agents through HPLC separation
  • Method for measuring related substances in Riociguat raw material agents through HPLC separation

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0033] Embodiment 1 specificity experiment

[0034] Chromatographic conditions:

[0035] Instrument: Agilent HPLC 1260;

[0036] Chromatographic column: Phenomenon C18Gemini 110A, 4.6×250mm, 5μm;

[0037] Detector: UV detector, detection wavelength 237nm;

[0038] Flow rate: 1.0ml / min;

[0039] Column temperature: 40°C;

[0040] Gradient elution:

[0041] time (min) Phase A% (volume ratio) Phase B% (volume ratio) 0 90 10 5 90 10 30 30 70 60 30 70 61 90 10 70 90 10

[0042] Phase A: 0.01mol / L sodium perchlorate solution (phosphoric acid adjusts the pH value to 2.5): acetonitrile=90:10, volume ratio, wherein the concentration of phosphoric acid solution is about 85%, w / v;

[0043] Phase B: acetonitrile.

[0044] Experimental steps:

[0045] Diluent (blank solution): DMF: (20% acetonitrile aqueous solution) = 1:9, volume ratio.

[0046] The test solution: Take about 25mg of riociguat, accurately weigh it into a 50mL m...

Embodiment 2

[0052] Embodiment 2 durability experiment

[0053] This embodiment examines the durability of the chromatographic method by changing the parameters of some chromatographic conditions, based on the following chromatographic conditions:

[0054] Instrument: Agilent 1260 high performance liquid chromatography;

[0055]Chromatographic column: Phenomenon C18Gemini 110A, 4.6×250mm, 5μm;

[0056] Detector: UV detector, detection wavelength 237nm;

[0057] Flow rate: 1.0ml / min;

[0058] Column temperature: 40°C;

[0059] Gradient elution:

[0060] time (min) Phase A% (volume ratio) Phase B% (volume ratio) 0 90 10 5 90 10 30 30 70 60 30 70 61 90 10 70 90 10

[0061] Phase A: 0.01mol / L sodium perchlorate solution (phosphoric acid to adjust the pH value to 2.5): acetonitrile=90:10, volume ratio, wherein the concentration of phosphoric acid solution is about 85%, w / v;

[0062] Phase B: acetonitrile.

[0063] Investigate the adap...

Embodiment 3

[0070] Embodiment 3 detects limit limit experiment

[0071] The chromatographic conditions are as described in Example 1.

[0072] Diluent (blank solution): DMF: (20% acetonitrile aqueous solution) = 1:9, volume ratio.

[0073] Detection limit solution: take ROCG-triamine, ROCG-ethyl acetate, ROCG-m-fluorine impurity and riociguat, add appropriate amount of DMF to dissolve, dilute to make a series of solutions with different concentrations, and measure according to law. When the peak height of the main peak is 3 times the peak height of the noise, the concentration or amount of the substance is the detection limit of the substance; when the peak height of the main peak is 10 times the peak height of the noise, the concentration or amount of the substance is the detection limit of the substance limit of quantification. The results are shown in Table 3 below.

[0074] table 3

[0075] detection limit Percentage of the test product Injection amount (μg) Signal...

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Abstract

The invention discloses a method for measuring related substances in Riociguat raw material agents through HPLC separation, and relates to the technical field of high performance liquid chromatographic analysis method. The method for measuring the related substances in the Riociguat raw material agents through the HPLC separation comprises the steps of adopting an octadecylsilane bonded phase or an octanesilane bonded phase as a color spectrum of filler, adopting a mobile phase composed of a buffer salt solution adopted as an A phase or a mixed solution of the buffer salt solution and an organic solution and an organic solution adopted as a B phase to conduct elution, and adopting an ultraviolet detector as a detector to measure the related substances in the Riociguat raw material agents. According to the method for measuring the related substances in the Riociguat raw material agents through the HPLC separation, the content of the related substances in the Riociguat raw material agents can be quickly measured, and the method is particularly suitable for separating detection of the content of impurities of ROCG-triamine, ROCG-methyl formate and ROCG-m-fluorine.

Description

technical field [0001] The invention relates to the technical field of high-performance liquid chromatography analysis methods, in particular to a method for separating and measuring related substances in riociguat raw materials by using HPLC. Background technique [0002] Riociguat, referred to as ROCG, is a compound that can stimulate soluble guanylate cyclase (sGC) developed by German Bayer Pharmaceutical Company. Vascular disease and / or sexual dysfunction. At present, the oral tablet developed by Bayer Pharmaceuticals for the treatment of pulmonary arterial hypertension (PAH) has been approved by the FDA under the trade name Adempas. [0003] Three preparation methods of Riociguat, its isomers and hydrates are disclosed in Chinese patent CN1330649C, wherein one of the preparation methods involves 2-[1-(2-fluorobenzyl)-1H-pyrazolo [3,4-b]pyridin-3-yl]-4,5,6-pyrimidine triamine (hereinafter referred to as ROCG-triamine, the preparation method of this compound has been di...

Claims

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Application Information

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IPC IPC(8): G01N30/02
CPCG01N30/02
Inventor 何新欢宋杰
Owner 韩庆亮
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