Method for separating and determining rivaroxaban and impurities thereof, and application thereof

A technology for rivaroxaban and impurities, which is applied in the field of analytical chemistry, can solve the problem of not being able to separate and detect rivaroxaban and related impurities at the same time, and achieves a simple and feasible method, strong specificity, and ensured quality controllable. Effect

Active Publication Date: 2015-10-28
CHONGQING HUAPONT PHARMA
View PDF5 Cites 14 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The patent application number CN103558326A discloses a method for determining the content of rivaroxaban in rivaroxaban tablets. In this method, only the content of rivaroxaban in the product can be detected, and simultaneous separation and detection of rivaroxaban cannot be achieved. The purpose of rivaroxaban and its related impurities; the patent application number WO2012035057 discloses a method for the separation and determination of rivaroxaban and its related impurities by liquid chromatography, and the detected impuri

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Method for separating and determining rivaroxaban and impurities thereof, and application thereof
  • Method for separating and determining rivaroxaban and impurities thereof, and application thereof
  • Method for separating and determining rivaroxaban and impurities thereof, and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Example Embodiment

[0049] Example 1 Separation and determination of rivaroxaban and its impurities

[0050] (1) Take appropriate amounts of rivaroxaban and impurity reference substance, and dissolve the sample with 30% acetonitrile aqueous solution to obtain a sample solution;

[0051] (2) Preparation of mobile phase A: Weigh 2.0 g of sodium pentane sulfonate, pipette 2.0 ml of phosphoric acid into a 1000 ml volumetric flask, add water to dissolve and dilute to the mark, adjust the pH value to the mark with 1 mol / L sodium hydroxide solution 4.0±0.1; mobile phase B is acetonitrile;

[0052] (3) Take 10μl of the sample solution from step (1) and inject it into a chromatograph model Shimadzu LC-20AT, the column model is Purospher Star RP-18, set the mobile phase flow rate to 1.0ml / min, the detection wavelength to 250nm, The temperature of the column oven is 30℃;

[0053] Table 1 The volume of mobile phase A and mobile phase B for linear gradient elution

[0054] Time (min)

[0055] Perform linear gradie...

Example Embodiment

[0056] Example 2 Chromatographic detection of rivaroxaban and its impurities

[0057] The diluent was used as a blank control sample, and the sample solution described in step 1) in Example 1 was used as the test sample. The diluent and the sample solution were taken and injected according to the chromatographic conditions of the method in Example 1, and the chromatogram was recorded. The measurement results are shown in Table 2. HPLC chart see figure 1 , figure 2 .

[0058] Table 2 Test results

[0059]

[0060] The test results show that the diluent does not interfere with the detection of the test product; the number of theoretical plates of each main impurity peak is greater than 10,000; the resolution between each chromatographic peak is greater than 1.5; it can be seen that this method has high column efficiency and good separation effect. Strong specificity.

Example Embodiment

[0061] Example 3 Comparative Example of No Acidic Ion Pair Reagent

[0062] The phosphate buffer solution without acidic ion pair reagent is used as mobile phase A, acetonitrile is used as mobile phase B, the detection wavelength is 250nm, the flow rate is 1.0ml / min, and the gradient program is as follows:

[0063] Time (min)

[0064] Take the sample solution described in step 1) in Example 1, and record the chromatogram. The results are shown in image 3 .

[0065] The test results show that, under the chromatographic conditions in the comparative example, impurity H is a split deformation peak, impurity E and impurity F cannot be effectively separated, which affects the accurate quantitative detection of impurities. The results of the comparative examples show that the present invention can better separate and detect 10 process impurities in rivaroxaban and its preparations.

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

PUM

PropertyMeasurementUnit
Wavelengthaaaaaaaaaa
Login to view more

Abstract

The invention relates to a method for separating and determining rivaroxaban and impurities thereof, and application thereof, belonging to the technical field of analytical chemistry. A reagent composition used for separating and determining rivaroxaban and impurities thereof comprises a reagent A and a reagent B, where the reagent A is an inorganic salt buffer system with an acidic ion-pairing agent which has a concentration of 0.2 to 4.0 g/L, and the reagent B is an organic solvent. The method for separating and determining rivaroxaban and impurities by using the reagent composition comprises the following steps: dissolving rivaroxaban in an aqueous acetonitrile solution so as to obtain a sample solution; preparing a mobile phase; injecting the sample solution into a separation and detection system and carrying out separation and detection on the sample solution by using the mobile phase so as to obtain eluate; and allowing the eluate to enter a detector for determination. The method provided by the invention can completely separate rivaroxaban from the impurities thereof at the same time and has the advantages of simplicity, high sensitivity, short analysis time, strong specificity, good reproducibility and capacity of simultaneously and effectively separating and determining contents of relevant substances in the bulk drug and preparations of rivaroxaban.

Description

technical field [0001] The invention belongs to the field of analytical chemistry, and in particular relates to a method and application for simultaneously separating and measuring rivaroxaban and its impurities. Background technique [0002] Rivaroxaban (trade name: Xarelto) is a new oral anticoagulant drug developed by Bayer Pharmaceuticals in Germany. It is mainly used for adult patients undergoing elective hip or knee replacement surgery to prevent venous thrombosis. This product is highly selective and competitive, with low bleeding risk and good safety. Rivaroxaban chemical name: 5-chloro-nitrogen-({(5S)-2-oxo-3-[4-(3-oxo-4-morpholinyl)phenyl]-1,3-oxazolidine -5-yl}methyl)-2-thiophene-carboxamide, the molecular formula is C 19 h 18 ClN 3 o 5 S. The structural formula of rivaroxaban is: [0003] [0004] Generally speaking, the total content of a drug impurity should be less than 1.0%, and the content of a single impurity should be less than 0.1%. For the impu...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

Application Information

Patent Timeline
no application Login to view more
IPC IPC(8): G01N30/02
Inventor 张荣张波
Owner CHONGQING HUAPONT PHARMA
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Try Eureka
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap