盐酸替哌拉索杂质结构鉴定

目的：对盐酸替哌拉索碱性强制降解杂质进行结构鉴定，并建立盐酸替哌拉索及有关物质的HPLC测定方法。方法：以HPLC法对碱性强制降解杂质进行分析，并通过制备得到杂质单体，根据Q-TOF/MS以及1H-NMR、13C-NMR、2D-NMR技术对其结构进行分析确证。采用Waters Atlantis T3柱（4.6 mm×150 mm，3μm）对盐酸替哌拉索的降解杂质和工艺杂质进行定量分析，以磷酸二氢钾、庚烷磺酸钠缓冲液（pH 3.0）-甲醇为流动相，梯度洗脱，检测波长为210 nm。结果：综合解析确证盐酸替哌拉索碱性强制降解杂质结构为4-（（（5-氯-2，6-二酮-1，2，3，6-四氢嘧啶-4-基）甲基）氨基）丁酰胺。在该HPLC测定方法条件下主峰与各杂质峰间能达到基线分离，盐酸替哌拉索及其杂质检测限为0.05μg·mL-1，定量限为0.15μg·mL-1。结论：本研究鉴定了盐酸替哌拉索原药在剧烈条件下产生的杂质；此高效液相色谱法选择性高、重复性好，可作为盐酸替哌拉索原药质量控制的方法。

Identification of a Degradation Impurity of Tipiracil Hydrochloride

Objective: To identify the alkaline degradation product of tipiracil hydrochloride and estab-lish an HPLC method for the determination of its related substances. Methods: The alkaline degradation product was analyzed by HPLC and its structural confirmation was unambiguously carried out by prepara-tion followed by characterization using Q-TOF/MS and NMR. The test for degradation and process impuri-ties of tipiracil hydrochloride is based on a Waters Atlantis T3 column (4.6 mm ×150 mm, 3μm); the mobile phase consisted of potassium dihydrogen phosphate and sodium heptane-sulphonate buffer solution (adjust to pH 3.0) - methanol with gradient elution; the detection wavelength was 210 nm. Results: Based on the spectral data, the alkaline degradation product of tipiracil hydrochloride was characterized as 4-(((5-chloro-2,6-dioxo-1,2,3,6-tetrahydropyrimidin-4-yl)methyl)amino)butanamide. The main peak and every impurity peak were separated well. The LOD and LOQ of tipiracil hydrochloride and its impurities were 0.05μg· mL-1 and 0.15μg·mL-1, respectively. Conclusion: The investigation identified the impurity of tipiracil hy-drochloride produced under high pH conditions and the highly selective and reproducible HPLC offered an option in the quality control of tipiracil hydrochloride.