A validated UHPLC-QTOF-MS method for quantification of metformin and teneligliptin in rat plasma: Application to pharmacokinetic interaction study
A validated UHPLC-QTOF-MS method for quantification of metformin and teneligliptin in rat plasma: Application to pharmacokinetic interaction study
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DOI：
10.1016/j.jpba.2017.05.026
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发表时间：
2017-09-05
影响因子：
3.4
通讯作者：
Satheeshkumar, Nanjappan
中科院分区：
文献类型：
--
作者：
Paul, David;Allakonda, Lingesh;Satheeshkumar, Nanjappan
在本研究中，开发了一种灵敏的UHPLC-QTOF-MS方法，并使用达格列净作为内标物（IS）对大鼠血浆中的二甲双胍（MET）和替尼格列汀（TEN）进行了定量验证。在Acquity UPLC HSS Cyano色谱柱（100 mm x 2.1 mm，1.8 μ m）上进行色谱分离，使用由0.1%甲酸和乙腈组成的梯度移动的相系统，流速为0.4 mL/min，运行时间为6 min。使用蛋白沉淀法作为样品制备方法。在正离子电喷雾电离模式下，在MET的m/z 130.1085、TEN的m/z 427.2277和IS的m/z 409.1623处检测目标离子[M+H]（+）。在0.98-1000 ng/mL范围内评估MET和TEN的线性。根据US-FDA和EMA生物分析指南对开发的测定进行了验证，并成功应用于SD大鼠的药代动力学相互作用研究。当在大鼠中联合给药时，观察到MET和TEN的AUC水平增加1.1倍。(C)2017爱思唯尔B. V.保留所有权利。
In this study a sensitive UHPLC-QTOF-MS method was developed and validated for the quantitation of the metformin (MET) and teneligliptin (TEN) in rat plasma using dapagliflozin as an internal standard (IS). Chromatographic separation were carried out on a Acquity UPLC HSS Cyano column (100 mm x 2.1 mm, 1.8 mu m) using gradient mobile phase system consisting of 0.1% formic acid and acetonitrile at a flow rate of 0.4 mL/min, within a run time of 6 min. Protein precipitation method was used as sample preparation approach. Detection of target ions [M+H](+) at m/z 130.1085 for MET, m/z 427.2277 for TEN and m/z 409.1623 for IS was performed at positive ion electrospray ionization mode. Linearity was assessed in the range of 0.98-1000 ng/mL for both MET and TEN. The developed assay was validated as per US-FDA and EMA bioanalytical guidelines and successfully applied to pharmacokinetic interaction study in SD rats. A 1.1 fold increment in the AUC levels of MET and TEN was observed when co-administered together in rats. (C) 2017 Elsevier B.V. All rights reserved.