Photostability evaluation of manidipine tablets and structural determination of its photoproducts

IF 1.8 4区化学 Q3 CHEMISTRY, ANALYTICAL

Analytical Sciences Pub Date : 2024-06-11 DOI:10.1007/s44211-024-00613-8

Kohei Kawabata, Kyoka Hirai, Shiori Akimoto, Masanori Inagaki, Hiroyuki Nishi

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Abstract

Manidipine (MP) is a dihydropyridine drug, which is treated for the reduction of high blood pressure. The aim of this study is to clarify the photochemical behavior of MP in the case of ultraviolet light (UV) irradiation for MP tablets (Calslot^® tablets). The tablets and its altered forms (powders and suspensions) were UV-irradiated using a black light, and residual amounts of active pharmaceutical ingredients (APIs) were monitored by high-performance liquid chromatography (HPLC). Due to the photoproducts of MP were detected in HPLC chromatograms, the elucidation of their chemical structures was carried out utilizing electrospray ionization tandem mass spectrometry (LC–ESI–MS/MS). As a result, APIs in Calslot^® tablets were almost completely photodegraded in the case that Calslot^® tablets were suspended in an aqueous media along with the generation of some MP photoproducts. LC–ESI–MS/MS analysis clarified the chemical structures of three MP photoproducts, indicating that they were a pyridine analogue, benzophenone and a hydrolysate. Benzophenone was a main MP photoproduct. It was possible that MP might be firstly oxidized to form its pyridine analogue, followed by the oxidation of a dimethyl methylene moiety. This moiety seemed to be eliminated as a benzophenone, and the cleavage of an ester bond of the residual moiety resulted in the generation of a hydrolysate. Finally, toxicological potencies of MP and its photoproducts were predicted in silico toxicity evaluation, suggesting some of biological effects of the photoproducts might be altered compared with MP.

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马尼地平片剂的光稳定性评价及其光生成物的结构测定。

马尼地平（MP）是一种二氢吡啶类药物，用于降低高血压。本研究旨在阐明马尼地平片剂（Calslot® 片剂）在紫外线（UV）照射下的光化学行为。使用黑光灯对片剂及其变体（粉末和悬浮剂）进行紫外线照射，并通过高效液相色谱法（HPLC）监测活性药物成分（API）的残留量。由于在 HPLC 色谱图中检测到了 MP 的光产物，因此利用电喷雾离子化串联质谱法（LC-ESI-MS/MS）对其化学结构进行了阐释。结果表明，当 Calslot® 片剂悬浮在水介质中时，Calslot® 片剂中的原料药几乎完全被光降解，同时产生了一些 MP 光产物。LC-ESI-MS/MS 分析明确了三种 MP 光产物的化学结构，表明它们分别是吡啶类似物、二苯甲酮和水解物。二苯甲酮是 MP 的主要光反应产物。MP 可能首先被氧化形成吡啶类似物，然后二甲基亚甲基被氧化。该分子似乎以二苯甲酮的形式被消除，残留分子的酯键裂解后生成水解物。最后，在硅毒性评估中预测了 MP 及其光反应产物的毒性，表明与 MP 相比，光反应产物的某些生物效应可能会发生变化。

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来源期刊

Analytical Sciences 化学-分析化学

CiteScore

2.90

自引率

18.80%

发文量

232

审稿时长

1 months

期刊介绍： Analytical Sciences is an international journal published monthly by The Japan Society for Analytical Chemistry. The journal publishes papers on all aspects of the theory and practice of analytical sciences, including fundamental and applied, inorganic and organic, wet chemical and instrumental methods. This publication is supported in part by the Grant-in-Aid for Publication of Scientific Research Result of the Japanese Ministry of Education, Culture, Sports, Science and Technology.