Li Meng-Fang, Hu Xiao-Xia, Ma Ai-Qun
Department of Cardiovascular Medicine, First Affiliated Hospital of Xi'an Jiaotong University, China.
Key Laboratory of Molecular Cardiology, Shaanxi Province, China.
Biomed Chromatogr. 2017 Oct;31(10). doi: 10.1002/bmc.3975. Epub 2017 May 12.
Omarigliptin is a novel long-acting dipeptidyl peptidase-4 inhibitor used for the treatment of type 2 diabetes. In this work, a sensitive and selective ultra-high pressure liquid chromatography tandem mass spectrometry method was developed and validated for the determination of omarigliptin in rat plasma. Sample preparation was performed by protein precipitation with acetonitrile. Chromatographic separation of analytes was achieved on an RRHD Eclipse Plus C18 column (2.1 × 50 mm, 1.8 μm), using gradient mobile phase (0.1% formic acid-acetonitrile) at a flow rate of 0.4 mL/min. Detection was performed in multiple reaction monitoring mode, with target fragment ions m/z 399.1 → 152.9 for omarigliptin and m/z 237.1 → 194 for the internal standard. The total run time was 4 min. Retention time of omarigliptin and internal standard was 1.25 and 2.12 min, respectively. Relative standard deviation (%) of the intra- and inter-day precision was below 10.0%, and accuracy was between 97.9% and 105.3%. Calibration curve was established over the range 2-5000 ng/mL with good linearity. The lower limit of quantification and limit of detection of omarigliptin were 2 and 0.25 ng/mL, respectively. Mean recoveries were in the range 87.3-95.1% for omarigliptin. No matrix effect was observed in this method. This novel method has been successfully applied to a pharmacokinetic study of omarigliptin in rats. The absolute bioavailability of omarigliptin was identified as high as 87.31%.
奥格列汀是一种新型长效二肽基肽酶-4抑制剂，用于治疗2型糖尿病。在本研究中，建立并验证了一种灵敏且选择性的超高效液相色谱串联质谱法，用于测定大鼠血浆中的奥格列汀。采用乙腈蛋白沉淀法进行样品制备。在RRHD Eclipse Plus C18柱（2.1×50 mm，1.8μm）上实现分析物的色谱分离，使用梯度流动相（0.1%甲酸-乙腈），流速为0.4 mL/min。采用多反应监测模式进行检测，奥格列汀的目标碎片离子为m/z 399.1→152.9，内标的目标碎片离子为m/z 237.1→194。总运行时间为4分钟。奥格列汀和内标的保留时间分别为1.25分钟和2.12分钟。日内和日间精密度的相对标准偏差（%）低于10.0%，准确度在97.9%至105.3%之间。在2-5000 ng/mL范围内建立校准曲线，线性良好。奥格列汀的定量下限和检测限分别为2 ng/mL和0.25 ng/mL。奥格列汀的平均回收率在87.3-95.1%范围内。该方法未观察到基质效应。这种新方法已成功应用于奥格列汀在大鼠体内的药代动力学研究。奥格列汀的绝对生物利用度高达87.31%。
