Development and Validation of Stability-Indicating UPLC Method for 9-Desmethyl-alpha-dihydrotetrabenazine
Development and Validation of Stability-Indicating UPLC Method for 9-Desmethyl-alpha-dihydrotetrabenazine
复制标题
9-去甲基-α-二氢丁苯那嗪稳定性指示 UPLC 方法的开发和验证
DOI：
10.1007/s10337-017-3388-x
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发表时间：
2017
期刊：
影响因子：
1.7
通讯作者：
Zhengping Chen
中科院分区：
文献类型：
--
作者：
Chunyi Liu;Danlu Xue;Xiaofeng Qin;Xiaomin Li;Jie Tang;Lihua Cao;Xijie Xu;Yi Liu;Zhengping Chen
建立了高效液相色谱法测定囊泡单胺转运体2显像剂11 C-α-DTBZ的前体9-去甲基-α-二氢丁苯那嗪（9-DM-α-DTBZ）的含量。化合物9-DM-α-DTBZ在酸性、碱性、氧化、热和光解等强制降解条件下进行降解。9-DM-α-DTBZ在氧化条件下发生降解，而在其他强制降解条件下未发生明显降解。对于9-DM-α-DTBZ及其降解产物的色谱分离，使用Acquity UPLC BEH C18色谱柱（2.1 × 100 mm，1.7 μm）和20：80（v/v）甲醇/乙酸铵缓冲液（pH 4.5，10 mM）的移动的流动相。使用PDA检测器以0.30 mL min−1的流速定量测定9-DM-α-DTBZ。进一步利用UPLC-MS分析来表征两种降解产物。根据USP指导原则，对拟定方法的线性、准确度、精密度、耐用性、检测限（LOD）和定量限（LOQ）进行了充分验证。线性回归分析显示，在0.001-1.00 mg mL−1（n= 6）浓度范围内线性关系良好（r2= 0.9995）。该方法具有良好的精密度（1.14-1.35% RSD）和回收率（98.91-101.23%）。此外，9-DM-α-DTBZ的LOD和LOQ分别为0.30和1.00 μg mL−1。结果表明，该方法可用于常规生产样品的质量评价，也可用于稳定性试验。
A stability-indicating UPLC method was developed for quantitative determination of 9-desmethyl-α-dihydrotetrabenazine (9-DM-α-DTBZ), the precursor for preparing a widely used vesicular monoamine transporter 2 imaging agent11C-α-DTBZ. Compound 9-DM-α-DTBZ was subjected to various stress conditions consisting of acidic, alkaline, oxidative, thermal and photolytic forced degradation. The decomposition of 9-DM-α-DTBZ was observed under oxidative condition, whereas no obvious degradation was shown under the other stress conditions. For chromatographic separation of 9-DM-α-DTBZ and its degradation products, an Acquity UPLC BEH C18 column (2.1 × 100 mm, 1.7 μm) and a mobile phase of 20:80 (v/v) methanol/ammonium acetate buffer (pH 4.5, 10 mM) were used. Quantitative determination of 9-DM-α-DTBZ was performed using a PDA detector at a flow rate of 0.30 mL min−1. UPLC–MS analysis was further utilized to characterize the two degradation products. The proposed method was fully validated as per USP guidelines with respect to linearity, accuracy, precision, robustness, limit of detection (LOD) and limit of quantification (LOQ). The linear regression analysis showed a good linear relationship (r2= 0.9995) in the concentration range of 0.001–1.00 mg mL−1(n= 6). The assay method was found to have good precision (1.14–1.35% RSD) and recovery (98.91–101.23%). Additionally, the LOD and LOQ of 9-DM-α-DTBZ were 0.30 and 1.00 μg mL−1, respectively. These results indicated that the present method could be used to evaluate the quality of regular production samples and also used in stability assays.