Use of High Performance Liquid Chromatography in the Analysis of a New Substance VMA-10-18
Introduction. Quinazoline derivatives have a wide range of pharmacological properties, which makes this group quite unique among other classes of heterocyclic compounds. Substance VMA-10-18, which has cerebrovasodilating, antidepressant, anxiolytic and nootropic properties, may become a promising ne...
| Main Authors: | , , |
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| Format: | Article |
| Language: | Russian |
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LLC Center of Pharmaceutical Analytics (LLC «CPHA»)
2021-08-01
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| Series: | Разработка и регистрация лекарственных средств |
| Subjects: | |
| Online Access: | https://www.pharmjournal.ru/jour/article/view/1003 |
| Summary: | Introduction. Quinazoline derivatives have a wide range of pharmacological properties, which makes this group quite unique among other classes of heterocyclic compounds. Substance VMA-10-18, which has cerebrovasodilating, antidepressant, anxiolytic and nootropic properties, may become a promising new drug. In this regard, an urgent task is to develop methods for standardizing this substance.Aim. Development of a method for the quantitation of related impurities of a new biologically active substance VMA-10-18 (Quinazophene) by HPLC with subsequent statistical processing of the results.Materials and methods. To develop the conditions for chromatographic analysis, was used a highly purified substance 3-[2-(4-methoxyphenylamino)-2-oxoethyl]-quinazolin-4(3H)-one, as well as its related impurities: impurity I (unsubstituted quinazolin-4(3H)-one) and impurity II (4-methoxychloroacetanilide). Test solutions were prepared using volumetric glassware of accuracy class 1. Ethyl alcohol 95 % was used as a solvent. Chromatography was performed using a Dionex UltiMate 3000 system (Dionex, United States) with a spectrophotometric detector. The analysis was carried out at a wavelength of 231 nm. Data collection and processing was carried out using the Chromeleon v.7 system. A mixture of acetonitrile and orthophosphoric acid was used as a mobile phase. The analysis was performed in an isocratic mode. The validation of the developed method was carried out taking into account the requirements of the State Pharmacopeia of Russian Federation XIV edition and the recommendations of the ICH.Results and discussion. The optimal conditions for chromatography of the VMA-10-18 substance and its impurities have been developed. It was found that for a clear separation of the peaks of the substance and impurities among themselves, the mobile phase should contain acetonitrile and orthophosphoric acid in a ratio of 80 : 20. The specificity of the method was determined by chromatography of ethyl alcohol in order to exclude its influence on the analysis results. The linearity and correctness of the method were determined at 7 levels of concentration of impurities of the substance. The correlation coefficient has exceeded 0.99. Also, the free term of the linear dependence equation (a) for both impurities was less than its confidence interval (Δа), which proves the absence of a systematic error of the method. When determining the "Convergence" indicator, the calculated relative standard deviation did not exceed 2 %. When determining the intralaboratory precision, Student's t-test and Fisher's F-test were calculated. Both indicators met the stated requirements.Conclusion. A method for the quantitative determination of impurities in the VMA-10-18 substance by HPLC has been developed and validated. |
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| ISSN: | 2305-2066 2658-5049 |