Sensitive detection of quinoline-derivatized sitagliptin in small volumes of human plasma by MALDI-TOF mass spectrometry

TALANTA

卷:218

Article

Li, Yi-Shan¹  Tseng, Wei-Lung²  Lu, Chi-Yu^1,3,4 

[1] Kaohsiung Med Univ, Coll Med, Dept Biochem, Kaohsiung 80708, Taiwan

[2] Natl Sun Yat Sen Univ, Coll Sci, Dept Chem, Kaohsiung 80424, Taiwan

[3] Natl Sun Yat Sen Univ, Inst Med Sci & Technol, Kaohsiung 80424, Taiwan

[4] Kaohsiung Med Univ Hosp, Dept Med Res, Kaohsiung 80708, Taiwan

关键词: Quinoline;    Microextraction;    Dipeptidyl peptidase 4 inhibitors;    Trace level;    Sitagliptin;   

DOI  :  10.1016/j.talanta.2020.121143

来源: Elsevier

【 摘 要 】

Dipeptidyl peptidase 4 (DPP-4) inhibitors are incretin-based medications used as oral antidiabetic agents for the treatment of type 2 diabetes. However, DPP-4 inhibitors produce side effects like acute pancreatitis, upper respiratory tract infection, nasopharyngitis, urinary tract infection, serious allergies, cardiovascular diseases, hemolysis, and retinopathy. Hence, the development of a fast and simple method to detect DPP-4 inhibitors in body fluids is important. In this study, we developed a derivatization-assisted microextraction method to enhance the detection sensitivity for trace levels of a DPP-4 inhibitor, sitagliptin, from a small volume (10 mu L) of human plasma by using matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS). Subjecting the analyte to 100 W microwave irradiation after derivatization using a quinoline alkylating reagent (8-bromomethyl quinilone, BrMQ) shortened the reaction time to similar to 120 s and allowed the target analyte to be easily extracted to a small volume of the organic layer (20 mu L). The analyte was then detected by MALDI-TOF MS using alpha-cyano-4-hydroxycinnamic acid as the matrix. The relative standard deviation and relative error were below 10% in intra-and inter-day assays. Using sitagliptin-d4 as an internal standard, the limits of quantitation and detection were found to be 0.03 mu g/mL and 0.01 mu g/mL, respectively. All the derivatization and extraction procedures described herein were of microliter grade. This method could effectively reduce the use of organic chemicals and solvents, thereby proving to be an eco-friendly strategy that will cause no harm to the environment.

【 授权许可】

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