High performance liquid chromatography (HPLC) detection method of Rivaroxaban

Abstract

The invention discloses a high performance liquid chromatography (HPLC) detection method of Rivaroxaban. The method comprises the following steps: a. preparing a test solution; b. preparing a reference solution; c. respectively detecting the test solution and the reference solution by adopting HPLC, wherein the detection conditions are as follow: the stationary phase of a chromatographic column is silica gel which is coated with amylose-tri ((S)-alpha-methyl phenyl carbamate) on the surface, the mobile phase of the chromatographic column is acetonitrile-water, the flow velocity is 0.5-1.5ml / min, the column temperature is 10-40 DEG C, and the detection wave length is 200nm-300nm. After the detection method is used, the degree of separation of Rivaroxaban and Rivaroxaban R isomer is more than 3.0, and more theoretical plates are available, so that the detection result accuracy is effectively prevented from being influenced by the interference of all components; furthermore, the detection method has the advantages of being accurate and reliable in detection results, short in analysis time, low in cost, simple and convenient in operation, etc.

Description

technical field [0001] The invention relates to a high performance liquid chromatography detection method for rivaroxaban. Background technique [0002] Rivaroxaban (Rivaroxaban), molecular formula: C 19 h 18 ClN 3 o 5 S, the chemical name is 5-chloro-nitrogen-({(5S)-2-oxo-3-[4-(3-oxo-4-morpholinyl)phenyl]-1,3-oxazolidine-5- Base} methyl)-2-thiophene-carboxamide, its chemical structure is as shown in formula A; Rivaroxaban is a new oral anticoagulant drug, and the rivaroxaban drug that has been approved for listing currently has Bayer Healthcare Rivaroxaban tablets (trade name: Xarelto) produced by the joint-stock company. [0003] [0004] The R isomer of rivaroxaban is the optical isomer (enantiomer) of rivaroxaban (ie, the S isomer of rivaroxaban), which will inevitably occur during the preparation of rivaroxaban. The R isomer of rivaroxaban exists at the same time; however, clinical studies have shown that the R isomer of rivaroxaban is much less effective than ...

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Problems solved by technology

[0006] At present, in the prior art, long and expensive chromatographic columns are used to analyze and detect the content of isomers in rivaroxaban; for example: Chinese patent CN 103217492A discloses a rivaroxaban optical isomer The method of separation and determination of body, it adopts the length of 250mm IC chromatographic column separation and determination of rivaroxaban S isomer and R isomer, this method has a small separation degree of rivaroxaban S isomer and R isomer due to the large peak width of the chromatographic peak, and at the same time There is the problem of long analysis time (the analysis time is as long as more than 17 minutes), if the retention time is shortened (that is, the analysis time is shortened), the separation degree of rivaroxaban S isomer and R isomer will be smaller (see CN 103217492 A Instructions for drawings image 3 ); Zhang Qianru (Zhang Qianru, Zhang Qi, Guo Xiaofeng, Guo Wenmin. Determination of Enantiomer Content in Rivaroxaban by HPLC. Chinese Pharmacist, 2014, Volume 17, Issue 10: 1629-1631.) and Susanne Roehrig (Susanne Roehrig, Alexander Straub, et al. Discovery of the Novel Antithrombotic Agent 5-Chloro-N-({(5S)-2-oxo-3-[4-(3-oxomorpholin-4-yl)phenyl] -1,3-oxazolidin-5-yl}methyl)thiophene-2-carboxamide (BAY 59-7939): An Oral, Direct Factor Xa Inhibitor. J. Med. Chem., 2005, 48(19): 5900-5908 .) also use a chromatographic column with a length of 250 mm to determine the content of rivaroxaban isomers, and there are also problems such as small resolution of rivaroxaban S isomers and R isomers, and long analysis time

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