Trelagliptin (TLN) is a novel once-weekly antidiabetic drug that enhanced the patient compliance in type 2 diabetes. TLN analysis and bioanalysis literature review showed many methods for TLN assay either in dosage form or as biological fluids (pharmacokinetic parameters), but all those methods did not consider the full details dealing with biological assay of TLN. Studies that included information about pharmacokinetic parameters did not mention the used analytical procedures for those determinations and parameters. Although some LC-MS/MS and UPLC-UV methods were reported for TLN bioassay in rats’ plasma, they used direct precipitation techniques, and the current described procedure showed lower LLOQ than all the reported methods in spite of that working on human plasma is more complicated than on rats’ plasma. In this study, LC-MS/MS bioanalysis of TLN in human plasma (4–1000 nM) was employed successfully with LLOQ of 4 nM which is lower than all reported methods in rats’ plasma followed by a preliminary pharmacokinetic study. Alogliptin was used as internal standard (IS) because of its structure similarity to TLN. Pharmacokinetic parameters of TLN were investigated in Egyptian volunteers, and they had been compared to Japanese. Liquid-liquid extraction showed more sensitive results than direct precipitation. The proposed method was successfully applied to a pharmacokinetic study conducted on Egyptian volunteers. No dose modification is required upon comparing the pharmacokinetic parameters of the current study and previous studies on non-Egyptian volunteers.

中文翻译：

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使用灵敏的 LC-MS/MS 研究埃及志愿者中曲格列汀的药代动力学参数：与日本人群的比较研究

曲格列汀 (TLN) 是一种每周一次的新型抗糖尿病药物，可提高 2 型糖尿病患者的依从性。TLN 分析和生物分析文献综述显示了许多以剂型或生物体液（药代动力学参数）形式进行 TLN 测定的方法，但所有这些方法都没有考虑处理 TLN 生物测定的全部细节。包括有关药代动力学参数信息的研究没有提及用于这些测定和参数的分析程序。尽管报告了一些 LC-MS/MS 和 UPLC-UV 方法用于大鼠血浆中的 TLN 生物测定，但它们使用了直接沉淀技术，并且当前描述的程序显示出比所有报告的方法更低的 LLOQ，尽管对人血浆进行了研究比大鼠血浆更复杂。在这项研究中，LC-MS/MS 对人血浆 (4–1000 nM) 中的 TLN 进行了成功的生物分析，LLOQ 为 4 nM，低于所有报告的大鼠血浆方法，随后进行了初步药代动力学研究。由于阿格列汀与 TLN 的结构相似，因此将其用作内标 (IS)。在埃及志愿者中研究了 TLN 的药代动力学参数，并将它们与日本人进行了比较。液-液萃取显示出比直接沉淀更灵敏的结果。所提出的方法已成功应用于对埃及志愿者进行的药代动力学研究。在比较当前研究的药代动力学参数和以前对非埃及志愿者的研究时，不需要调整剂量。