Method for analyzing lamotrigine by high performance liquid chromatography

Abstract

The invention provides a method for analyzing lamotrigine related substances by high performance liquid chromatography, which adopts a reversed-phase high performance liquid chromatographic column, takes octadecylsilane chemically bonded silica as a chromatographic column filler, takes methanol as a mobile phase A, takes a 0.2-0.8% triethylamine solution with the pH value of 4.2-5.0 as a mobile phase B, and adopts gradient elution. The method disclosed by the invention can be used for simultaneously detecting process impurities and degradation impurities related to lamotrigine, is relatively short in operation time, relatively smooth in base line and ideal in separation degree of main components and various impurities, and has relatively good specificity, stability and accuracy.

Description

technical field [0001] The invention relates to the field of drug analysis, in particular to a method for evaluating the quality of drugs by high performance liquid chromatography. Background technique [0002] Lamotrigine is a broad-spectrum antiepileptic drug of the phenyltriazine class, which is suitable for the first-line treatment of epilepsy in children over 12 years old and adults. It was first launched in Ireland in 1990 and launched in China in 2007. [0003] During the synthesis and storage of lamotrigine, various process impurities and degradation impurities will be produced, see Table 1 for details. [0004] Table 1 Known impurities of lamotrigine [0005] [0006] [0007] The related substances of lamotrigine in European Pharmacopoeia (EP8.0 / EP9.0 / EP10.3 version) are the same as the related substances of lamotrigine in British Pharmacopoeia (BP2017 / BP2018 / 2021 version). Disadvantages: Two different chromatographic systems are used to measure the related...

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Problems solved by technology

Disadvantages: Two different chromatographic systems are used to measure the related impurities respectively. Lamotrigine and adjacent impurities can be separated well, but the baseline of the gradient operation of this method has large fluctuations, and the gradient baseline changes greatly Where there are impurities peaking, which will affect the accuracy of the impurity detection

"United States Pharmacopoeia" (USP38 / USP40 / USP43) adopts different liquid phase detection methods for the related substances of lamotrigine raw materials and tablets. Effective detection of process impurities and degradation impurities related to lamotrigine

Huang Nuozhe et al. (Determination of related substances in lamotrigine by HPLC. Journal of Drug Analysis 2020; 40(03):495-501.) Referring to the detection method of lamotrigine in the EP9.0 Pharmacopoeia, the two liquid phases The method is combined into a liquid-phase method. Although it can detect impurity B, impurity C, and impurity D at the same time, the separation degree of impurity G and a certain oxidative degradation impurity is not ideal, and the process impurities 2,3-dichlorobenzoyl cyanide, 2,3-dichlorobenzoyl chloride and possible degradation impurity E, etc. could not be effectively detected, because the tolerance pH value range of commonly used chromatographic columns is 2-10, the mobile phase of this method is adjusted to a pH value of 2, which is not suitable for commonly used chromatographic columns. The damage of the column is large, and the mobile phase uses solid potassium dihydrogen phosphate configuration, which is easy to crystallize and block the liquid phase system in high organic phase or low temperature environment

[0008] Chen Sihan et al. (Determination of the content of lamotrigine tablets by HPLC method, North Pharmacy 2014 Volume 11 No. 7, P2 page) and Xia Jinhui et al. And the 19th Tianjin Chromatography Academic Report-Instrument Exhibition Collection, September 2010) reported the determination of related substances in lamotrigine tablets. According to these detection methods, the main peak of lamotrigine and impurity B The resolution is not ideal, and the effective simultaneous detection of process impurities and degradation impurities is not achieved

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