HPLC测定利格列汀的有关物质  

Determination of the Related Substances of Linagliptin by HPLC

作　　者：孙著叶 

机构地区：[1]日照市中医医院,山东日照276800

出　　处：《中国现代应用药学》2016年第4期451-455,共5页Chinese Journal of Modern Applied Pharmacy

摘　　要：目的建立梯度洗脱高效液相色谱法测定利格列汀原料杂质的方法。方法色谱柱为Agilent C18柱,流动相A为磷酸盐缓冲液（取磷酸二氢钠2.0 g,加水1 000 m L溶解,并用磷酸调节p H值至2.5±0.1）,流动相B为甲醇-乙腈（55∶45）,以1.0 m L·min^-1流速;检测波长为226 nm;柱温为30℃,进样量为10μL。结果 8-[（3R）-哌啶-3-氨基]-7-（2-丁炔基）-3,7-二氢-3-甲基-1-[（4-甲基-2-喹唑啉基）甲基]-1H-嘌呤-2,6-二酮（杂质A）、8-[（3R）-3-氨基-1-哌啶基]-7-（3-溴-2-丁烯基）-3,7-二氢-3-甲基-1-[（4-甲基-2-喹唑啉基）甲基]-1H-嘌呤-2,6-二酮（杂质B）、8-[（3R）-3-甲酰胺基-1-哌啶基]-（7-（2-丁炔基）-3,7-二氢-3-甲基-1-[（4-甲基-2-喹唑啉基）甲基]-1H-嘌呤-2,6-二酮（杂质C）和利格列汀及其他未知杂质均能达到很好的分离,且杂质A、杂质B、杂质C与利格列汀分别在0.59-5.91μg·m L？1（r=0.999 9）,0.59-5.86μg·m L？1（r=0.999 8）、0.58-5.79μg·m L^-1（r=0.999 5）和1.32-13.22μg·m L^-1（r=0.999 7）内具有良好的线性关系。杂质A、杂质B、杂质C平均回收率（n=9）分别为99.12%（RSD=2.9%）、99.35%（RSD=2.4%）和98.52%（RSD=1.1%）。结论本方法灵敏快速、准确、可靠,专属性强,可作为利格列汀的杂质检查。OBJECTIVE To establish an HPLC method for the determination of related substances linagliptin. METHODS The analysis was performed on C18 column by using a gradient method starting with mobile phase composed of phosphate buffer（sodium dihydrogen phosphate 2.0 g dissolved with 1000 mL waters, adjusted by phosphate to the pH of 2.5±0.1）： methanol and acetonitrile（55 ： 45） at the flow rate of 1.0 mL.min^-1 and the detection wavelength was set at 226 nm. RESULTS The related substances were completely separated from the main peak. The calibration curve were linear, the impurity A in range from 0.59 μg.mL^-1 to 5.91 μg.mL^- 1（r=0.999 9）, the impurity B in range from 0.59 μg.mL^-1 to 5.86 μg.mL^-1（r=0.999 8）, the purity C in range from 0.58 lag-mL-I to 5.79 ggmL-I（r=0.999 5） and linagliptin from 1.32 μg.mL^-1 to 13.22 μg.mL^-1（r=0.999 7） The average recoveries of the impurity A, the impurity B and the impurity C mentioned above were 99.12%（RSD=2.9%）, 99.35%（RSD=2.4%） and 98.52%（RSD=1.1%）, respectively. CONCLUSIONS The HPLC method has been developed for quality control, and detection of related substances of linagliptin with high sensitivity and specificity.

关 键 词：利格列汀 高效液相色谱 梯度洗脱 有关物质 

分 类 号：R917.101[医药卫生—药物分析学]