Method for separation and determination of Acitretin and its impurities

A technology of acitretin and impurities, which is applied in the field of separation and determination of acitretin and its impurities, can solve the problems of effective separation of the main peak, weak polarity, and ineffective separation, and achieve quality control, good sensitivity and high accuracy. Effect

Active Publication Date: 2022-07-29
CHONGQING HUABANGSHENGKAI PHARM
View PDF7 Cites 1 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

At present, Chinese Pharmacopoeia 2020 and European Pharmacopoeia 10.0 (the method is consistent with US Pharmacopoeia 43 edition / British Pharmacopoeia 2020 edition) respectively record a method for the separation and determination of acitretin and its related impurities by liquid chromatography. The impurities detected by the Pharmacopoeia are 4 related impurities (see ChP2020 for the structural formula), the impurities detected by the European Pharmacopoeia are 2 related impurities (see EP10.0 for the structural formula), and the impurities detected by the present invention are 8 related impurities. The structural formula of each impurity is See the table below, wherein the impurities A and B disclosed in EP10.0 are the same as the impurities A and B in the impurity list of the present invention, and the impurities disclosed in ChP2020 are 13-cis acitretin, 9-cis acitretin, and 11-cis Acitretin and 13-ethyl acitretin are respectively the same as impurities A, C, D and 13-ethyl acitretin of the present invention, and impurity E and impurity H in the present invention are all in EP10.0 and ChP2020 standards Impurities are not recorded, and in the chromatographic method recorded in EP10.0, impurities A, C, D, and E are completely overlapped, and 13-ethyl acitretin and the main peak are also completely overlapped. In the chromatographic method recorded in ChP2020, different The C18 chromatographic column has a great influence on the separation of impurities. For example, when the YMC-ODS-A chromatographic column is used, the impurity D and the main peak completely overlap and cannot be effectively separated. When using Waters XTerra RP18, the impurity A and the impurity D completely overlap and cannot be separated The main peak is effectively separated, and the impurity C overlaps with the main peak. When Alltima C18 is used, the impurity ACDE can be effectively separated, but the impurity B and impurity H cannot be eluted due to their weak polarity. So far, there is no public method reported to simultaneously Separation of 8 kinds of impurities recorded in the following table

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 separation and determination of Acitretin and its impurities
  • Method for separation and determination of Acitretin and its impurities
  • Method for separation and determination of Acitretin and its impurities

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0046] Select a chromatograph with a model of Shimadzu LC-20A, a chromatographic column model of Alltima C18 (250 × 4.6 mm, 5 μm), mobile phase A is 0.5% acetic acid water; mobile phase B is methanol; take the sample solution of step (1) 10μl was injected into the liquid chromatograph, the flow rate of the mobile phase was set to 1.5ml / min, the detection wavelength was 360nm, the temperature of the column oven was 25°C, and the data shown in Table 1 was followed by linear gradient elution to complete the sample solution. separation and measurement, when the sample separation and measurement results are as follows figure 1 shown.

[0047] Table 1 Volumes of Mobile Phase A and Mobile Phase B for Linear Gradient Elution

[0048]

Embodiment 2

[0049] Example 2 Limit of Quantitation and Limit of Detection

[0050] Quantitative limit solution: Precisely weigh each impurity reference substance, prepare a solution of a certain concentration, and dilute step by step to obtain a quantitative limit solution, as shown in Table 1.

[0051] Detection limit solution: Precisely pipette 5ml of quantitation limit solution, put it in a 10ml volumetric flask, add diluent to dilute to the mark, and shake well to obtain detection limit solution, as shown in Table 2.

[0052] test methods:

[0053] The above-mentioned quantitative limit solution was continuously injected for 3 times, and the detection limit solution was continuously injected for 2 times, and the ratio of the peak height of the main peak to the noise (signal-to-noise ratio) was calculated. Record the chromatogram, and the test results are shown in Table 1 and Table 2.

[0054]

[0055]

[0056] Table 2 Quantitative limit of Acitretin and various impurities

[...

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

No PUM Login to view more

Abstract

The invention belongs to the field of liquid chromatograph detection, in particular to a method for separating and measuring acitretin and its impurities. In the method, the stationary phase is an octadecylsilane-bonded silica gel chromatographic column, and a mobile phase consisting of a mobile phase A and a mobile phase B is used for elution and separation; the mobile phase A is a 0.2-1% glacial acetic acid aqueous solution, and the mobile phase A is Mobile phase B is an organic solvent. The method can completely separate and detect Acitretin and its eight impurities within 60 minutes, with high accuracy and good sensitivity.

Description

technical field [0001] The invention belongs to the field of liquid chromatograph detection, in particular to a method for separating and measuring acitretin and its impurities. Background technique [0002] This product was originally developed by Hoffmann-La Roche Company, and the product was transferred to Actavis in 2008. It is mainly used for severe psoriasis, including: erythrodermic psoriasis, localized generalized pustular psoriasis. Severe keratinopathy, such as congenital ichthyosis, pityriasis rubra pilaris, follicular keratosis. Others are dyskeratotic diseases that do not respond to other treatments. It was first listed in the United States in 2004, and was imported by the original researcher Actavis Group PTC ehf. Acitretin chemical name all-trans-9-(4-methoxy-2,3,6-trimethylphenyl)-3,7-dimethyl-2,4,6,8-nontetraene acid, molecular formula C 21 H 26 O 3 . The structural formula is: [0003] [0004] Generally speaking, the total impurity content of a ...

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 Patents(China)
IPC IPC(8): G01N30/02G01N30/06G01N30/34G01N30/74G01N30/86G01N30/88
CPCG01N30/02G01N30/06G01N30/34G01N30/74G01N30/8679G01N30/88G01N30/8634G01N2030/884G01N2030/8872
Inventor 周书荣蒋海龙兰昌云刘阔
Owner CHONGQING HUABANGSHENGKAI PHARM
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