Method of analyzing and determining genotoxic impurities in valsartan by HPLC

A genotoxicity and impurity technology, applied in analytical materials, measuring devices, material separation, etc., can solve problems such as genotoxic impurities of valsartan not seen

Active Publication Date: 2018-11-02
QILU PHARMA CO LTD
View PDF10 Cites 4 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

At present, there is no report of valsartan genotoxic impurity in USP, EP, JP, Chinese Pharmacopoeia and related literatures and patents

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 of analyzing and determining genotoxic impurities in valsartan by HPLC
  • Method of analyzing and determining genotoxic impurities in valsartan by HPLC
  • Method of analyzing and determining genotoxic impurities in valsartan by HPLC

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0035] Embodiment 1 specificity and impurity localization test

[0036] (1) Preparation of sample solution

[0037] Solvent: 90% acetonitrile in water

[0038] Positioning solution: Take the appropriate amount of valsartan, impurity Ⅰ and impurity Ⅱ, weigh them accurately, place them in different measuring bottles, add solvent (90% acetonitrile aqueous solution) to dissolve and dilute to make valsartan, impurity Ⅰ, impurity Ⅱ II. Each 0.1 mg / ml solution is used as a compound localization solution.

[0039] Specific solution: take 1.0 mg of impurity Ⅰ and impurity Ⅱ, weigh them accurately, put them in the same 1000ml measuring bottle, dissolve and dilute to 1000ml with solvent (90% acetonitrile aqueous solution), shake well, and store them as impurity Ⅰ and impurity Ⅱ Take 200mg of valsartan, accurately weighed, put it in a 10ml measuring bottle, and simultaneously accurately measure 1ml of impurity I and impurity II stock solution and put it in the measuring bottle, add solv...

Embodiment 2

[0054] Embodiment 2 limit of quantification

[0055] (1) Preparation of sample solution

[0056] Measurement of baseline noise: Precisely measure 20 μl of solvent, inject it into a liquid chromatograph, inject 3 needles continuously, and detect according to the chromatographic conditions described in the embodiment of the present invention. Record the noise of the blank baseline within the peak time range of impurity Ⅰ and impurity Ⅱ, and calculate the average value.

[0057] Preparation of quantitation limit solution: take appropriate amount of impurity I and impurity II, weigh them accurately, put them in the same measuring bottle, dissolve them with a solvent and gradually dilute them, and detect them according to the chromatographic conditions described in the examples of the present invention until they are diluted to impurity I and impurity II. The ratio of the peak height of II to the corresponding noise (i.e. signal-to-noise ratio, S / N) is about 10. At this time, the ...

Embodiment 3

[0064] Example 3 Linearity

[0065] (1) Sample solution preparation

[0066] Accurately weigh 20 mg each of impurity Ⅰ and impurity Ⅱ, put them in the same 100ml measuring bottle, add solvent to dissolve and dilute to the mark, and shake well; accurately measure 1ml, put it in a 10ml measuring bottle, add solvent to dilute to the mark, shake well, and use as Linear stock solution.

[0067] Precisely measure 1ml, 2ml, 3ml, 5ml, 7.5ml, 10ml, 15ml of the linear stock solution, put them in different 100ml measuring bottles, add solvent to dilute to the mark, shake well, and use them as 20%, 40%, and 60% of the limit respectively. %, 100%, 150%, 200%, 300% linear solution. According to the chromatographic conditions described in the present invention, the linear equation and the correlation coefficient are calculated.

[0068] (2) Chromatographic conditions

[0069] Chromatographic condition is the same as embodiment 1

[0070] (3) Test results

[0071] The test results show ...

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
particle diameteraaaaaaaaaa
lengthaaaaaaaaaa
wavelengthaaaaaaaaaa
Login to view more

Abstract

The invention provides a method of analyzing and determining genotoxic impurities in valsartan by HPLC (high performance liquid chromatography) and belongs to the technical field of pharmaceutical analysis. The method takes phenylsilane bonded silica gel as a stationary phase and a trifluoroacetic acid aqueous solution and an acetonitrile trifluoroacetate solution as a mobile phase and adopts a gradient elution manner; and the established high performance liquid phase analysis method can accurately determine the two potential genotoxic impurities in the valsartan, namely 4'-bromoethyl-2-cyanobiphenyl (the impurity I) and 4',4'-bisbromomethy-2-cyanobiphenyl (the impurity II). The HPLC-UV (ultraviolet) method is simple to operate and short in analysis time; the sensitivity can reach 0.5ppm;a reliable basis is provided for improvement of valsartan quality standards and research of other sartan genotoxic impurities.

Description

technical field [0001] The invention belongs to the technical field of drug analysis, and specifically discloses a HPLC method for the determination of two potential genotoxic impurities in valsartan: 4'-bromomethyl-2-cyanobiphenyl (impurity I) and 4',4 Pharmaceutical analysis method of '-dibromomethyl-2-cyanobiphenyl (impurity Ⅱ). Background technique [0002] Valsartan, the chemical name is N-pentanoyl-N-[[2'-(1H-tetrazol-5-yl)[1,1'-biphenyl]-4-yl]methyl]-L- Valine, molecular formula C 24 h 29 N 5 o 3 , the molecular weight is 435.52, and its structural formula is as follows: [0003] [0004] Valsartan is an angiotensin Ⅱ receptor antagonist (ARB) drug, and it is the only ARB product that has three indications for hypertension, heart failure and myocardial infarction approved by the US FDA. Since it was launched in the United States in 1997, rich clinical experience has proved the antihypertensive efficacy and cardiovascular protection properties of valsartan. S...

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
Patent Type & Authority Applications(China)
IPC IPC(8): G01N30/06G01N30/74G01N30/86
CPCG01N30/06G01N30/74G01N30/8634
Inventor 马超周英兰唐玮王永智周丽君韩燕刚
Owner QILU PHARMA CO LTD
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