Method for separation and determination of Acitretin and its impurities

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 ...

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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

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