Investigation of Pharmacokinetic Parameters of Trelagliptin in Egyptian Volunteers Using Sensitive LC-MS/MS: A Comparative Study with a Japanese Population.

Shereen Mowaka,Mariam M Tadros,Nermeen Ashoush,Bassam M Ayoub,Arun Srivastav

doi:10.1155/2021/9664099

Abstract

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.

Highlights

Trelagliptin (TLN, Figure 1) inhibits dipeptidyl peptidase-4 enzyme increasing GLP-1 to treat type 2 diabetes
Some LC-MS/MS and UPLC-UV methods were used for TLN bioassay in rats’ plasma [14,15,16,17,18], 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. e use of two extracting solvents’ mixture (TBME and DEE) besides the upgrading of the detector, to be mass spectrometry instead of photodiode array [15], has greatly encouraged the authors to go further within this preliminary pharmacokinetic study
Trelagliptin (TLN) is a novel once-weekly antidiabetic drug that enhanced the patient compliance in type 2 diabetes [20,21,22,23,24]

Summary

Introduction

Trelagliptin (TLN, Figure 1) inhibits dipeptidyl peptidase-4 enzyme increasing GLP-1 to treat type 2 diabetes. In addition to its insulin secretagogue effect, it improves insulin resistance [1] It had been approved for use in Japan in March 2015 by Takeda pharmaceutical Company as. Some LC-MS/MS and UPLC-UV methods were used for TLN bioassay in rats’ plasma [14,15,16,17,18], 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. 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. Extraction of TLN from plasma enhanced using liquid-liquid extraction followed by vacuum evaporation that showed more sensitive results than direct precipitation

Methods

Results and Discussion

Conflicts of Interest