Simultaneous Quantification of Antidiabetic Agents in Human Plasma by a UPLC–QToF-MS Method

• DOI: 10.1371/journal.pone.0167107
• Publication Date: 2016-12-08T13:31:54Z
• Authors: Mariana Millan Fachi; Letícia Bonancio ...; Letícia Paula Leo...; Thais Martins Gui...; Roberto Pontarolo
• Keywords: Science; Q; R; Reproducibility of Results; 01 natural sciences; Mass Spectrometry; 0104 chemical sciences; Limit of Detection; Calibration; Medicine; Humans; Hypoglycemic Agents; Research Article; Chromatography, Liquid

An ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry method for the simultaneous quantification of chlorpropamide, glibenclamide, gliclazide, glimepiride, metformin, nateglinide, pioglitazone, rosiglitazone, and vildagliptin in human plasma was developed and validated, using isoniazid and sulfaquinoxaline as internal standards. Following plasma protein precipitation using acetonitrile with 1% formic acid, chromatographic separation was performed on a cyano column using gradient elution with water and acetonitrile, both containing 0.1% formic acid. Detection was performed in a quadrupole time-of-flight analyzer, using electrospray ionization operated in the positive mode. Data from validation studies demonstrated that the new method is highly sensitive, selective, precise (RSD < 10%), accurate (RE < 12%), linear (r > 0.99), free of matrix and has no residual effects. The developed method was successfully applied to volunteers' plasma samples. Hence, this method was demonstrated to be appropriate for clinical monitoring of antidiabetic agents.