西格列汀杂质的分析研究

摘要：西格列汀是由美国Merck默克公司研制出的，美国食品药品管理局在2006年10月17号批准其磷酸盐(商品名Januvia)上市，可用于治疗2 型糖尿病。本文主要建立了西格列汀、TTP、Boc丁酸的高效液相色谱（HPLC）分析分离方法。使用安捷伦Agilent 1220高效液相色谱仪进行方法的探索，最终得出的液相方法为：使用Phenomenex Luna 5μm C18(2) 100A(250*4.6mm)柱，再使用0.005mol/L磷酸二氢钾溶液，用2mol/l氢氧化钾溶液将其pH调至pH=6.2的作为缓冲盐，使用该缓冲盐与乙腈作为流动相，进行梯度洗脱。流速设定为1.0mL/min，柱温30℃，进样量为5μL，检测波长设定在205nm，西格列汀、TTP、Boc丁酸在20分钟内实现了分离。使用此液相方法，能够使得西格列汀、TTP、Boc丁酸良好地分离开来。通过方法验证，更说明了此高效液相色谱方法操作简单、灵敏度高、重现性好。43481

毕业论文关键词：西格列汀；杂质；高效液相色谱；

Analysis of Sitagliptin impurities

Abstract: Sitagliptin was developed by the Merck & Co Inc, and U.S. Food and Drug Administration approved its phosphate (Januvia) on 17th October, 2006, and it could be used for the treatment of type 2 diabetes. In this paper, a high performance liquid chromatography (HPLC) method for determination and separation of Sitagliptin, TTP and Boc acid was established. Agilent 1220 high performance liquid chromatograph was used for exploration, and the final results of the liquid phase method was as bellow. A Phenomenex Luna 5μm C18(2) 100A(250*4.6mm) was used in this method. The buffer solution is that using 2mol/L KOH solution to adjust PH of 0.005mol/L KH2PO4 solution to 6.2. The gradient elution of acetonitrile and buffer solution as mobile phases was performed at a flow rate of 1.0 mL /min. The column temperature was set at 30℃. Sample volume was 5μL, and detection wavelength was 205nm. The separation of Sitagliptin, TTP and Boc acid was completed within 20 minutes. Using this HPLC method could make Sitagliptin, TTP and Boc acid well separated. By verification of this method, it showed that this method is convenient, sensitive and reproducible.

Key words: Sitagliptin; impurities; High performance liquid chromatography;

1 前言 1

1.1 糖尿病的概述 1

1.1.1 糖尿病的现状 1

1.1.2 糖尿病的定义及诊断标准 1

1.1.3 糖尿病的分型 1

1.1.4 糖尿病的治疗 2

1.2 治疗2型糖尿病的降糖药物 3

1.3 二肽基肽酶Ⅳ(DPP- 4) 抑制剂 4

1.4 西格列汀 5

1.4.1 西格列汀 5

1.4.2 磷酸西格列汀的应用——磷酸西格列汀片 5

1.4.3 磷酸西格列汀的合成路线 6

1.5 西格列汀杂质 7

1.5.1 (R)-3-(叔丁氧羰基)氨基-4-(2,4,5-三氟苯基)丁酸 7

1.5.2 3-三氟甲基-5,6,7,8-四氢-[1,2,4]-三唑[4,3-a]并吡嗪盐酸盐 7

2 研究本课题的目的和意义 8

3 实验内容 9

3.1 实验拟使用的原料试剂和实验设备 9

3.1.1实验拟使用的原料试剂 9

3.1.2实验拟使用的实验设备西格列汀杂质的分析研究:http://www.youerw.com/huaxue/lunwen_44343.html