Li X Q, Li J W, Li Q H, Yan Y, Duan J L, Cui Y N, Su Z B, Luo Q, Xu J R, DU Y F, Wang G L, Xie Y, Lu W L
State Key Laboratory of Natural and Biomimetic Drugs, Beijing Key Laboratory of Molecular Pharmaceutics and New Drug System, Peking University School of Pharmaceutical Sciences, Beijing 100191, China.
Academy for Advanced Interdisciplinary Studies, Peking University, Beijing 100871, China.
Beijing Da Xue Xue Bao Yi Xue Ban. 2019 Jun 18;51(3):467-476. doi: 10.19723/j.issn.1671-167X.2019.03.014.
Larotaxel is a new chemical structure drug, which has not been marketed worldwide. Accordingly, the standard identification and quantification methods for larotaxel remain unclear. The spectrometric analyses were performed for verifying weight molecular formula, molecular weight and chemical structure of larotaxel. Besides, a quantification method was developed for measuring larotaxel in the liposomes.
The molecular formula, molecular weight and chemical structure of larotaxel were studied by using mass spectrometry (MS), infra-red (IR), nuclear magnetic resonance (NMR) and ultraviolet-visible (UV-vis) spectrometric techniques. The absorption wavelength of larotaxel was investigated by UV-vis spectrophotometry full-wavelength scanning. Besides, a quantification method was developed by high performance liquid chromatography (HPLC), and then validated by measuring the encapsulation efficacy of larotaxel liposomes.
The four spectral characteristics of larotaxel were revealed and the corresponding standard spectra were defined. It was confirmed that larotaxel had the structure of tricyclic diterpenoids, with the molecular formula of C45H53NO14, the molecular weight of 831.900 1, and the maximum absorption wavelength of 230 nm. The quantitative method of larotaxel was established by using HPLC with a reversed phase C18 column (5 μm, 250 mm×4.6 mm), a mobile phase of acetonitrile-water (75:25, volume/volume), and a detection wavelength of 230 nm. The validation study exhibited that the established HPLC method was stable, and had a high recovery and precision in the quantitative measurement of larotaxel in liposomes. In addition, a new kind of larotaxel liposomes was also successfully prepared. The particle size of the liposomes was about 105 nm, with an even size distribution. And the encapsulation efficiency of larotaxel in the liposomes was above 80%.
The present study offers reference standard spectra of larotaxel, including MS, IR, NMR, and UV-vis, and confirms the molecular formula, molecular weight and chemical structure of larotaxel. Besides, the study develops a rapid HPLC method for quality control of larotaxel liposomes.
拉罗他赛是一种新化学结构药物，尚未在全球上市。因此，拉罗他赛的标准鉴别和定量方法仍不明确。进行光谱分析以验证拉罗他赛的分子量分子式、分子量和化学结构。此外，还开发了一种用于测定脂质体中拉罗他赛的定量方法。
采用质谱（MS）、红外（IR）、核磁共振（NMR）和紫外可见（UV-vis）光谱技术研究拉罗他赛的分子式、分子量和化学结构。通过紫外可见分光光度法全波长扫描研究拉罗他赛的吸收波长。此外，采用高效液相色谱（HPLC）开发了一种定量方法，然后通过测定拉罗他赛脂质体的包封率进行验证。
揭示了拉罗他赛的四个光谱特征并定义了相应的标准光谱。证实拉罗他赛具有三环二萜类结构，分子式为C45H53NO14，分子量为831.900 1，最大吸收波长为230 nm。采用反相C18柱（5μm，250 mm×4.6 mm）、乙腈-水（75:25，体积/体积）流动相和230 nm检测波长的HPLC法建立了拉罗他赛的定量方法。验证研究表明，所建立的HPLC方法稳定，在脂质体中拉罗他赛的定量测定中具有较高的回收率和精密度。此外，还成功制备了一种新型拉罗他赛脂质体。脂质体的粒径约为105 nm，粒径分布均匀。拉罗他赛在脂质体中的包封率高于80%。
本研究提供了拉罗他赛的参考标准光谱，包括MS、IR、NMR和UV-vis，并确认了拉罗他赛的分子式、分子量和化学结构。此外，该研究开发了一种快速HPLC方法用于拉罗他赛脂质体的质量控制。
