Ultrafast Measurement of Metformin in the Clinical Setting Using Probe Electrospray Ionization Mass Spectrometry. Issue 1 (1st June 2022)

• Record Type: Journal Article
• Authors: Griffeuille, Pauline; El Balkhi, Souleiman; Bodeau, Sandra; Lamoureux, Fabien; Marquet, Pierre; Dulaurent, Sylvain; Saint-Marcoux, Franck
• Is Part Of: Journal of analytical toxicology. Volume 47:Issue 1(2023)
• Page Start: 89
• Page End: 95
• Publication Date: 2022-06-01
• Subjects: Drugs -- Analysis -- Periodicals; Drugs -- Toxicity testing -- Periodicals; 615.907
• DOI: 10.1093/jat/bkac034
• Languages: English
• ISSNs: 0146-4760

Abstract

Abstract: Metformin (MtF) is a treatment used for type 2 diabetes. Lactic acidosis (LA) is a frequent complication that can be either induced by or associated with elevated MtF plasma concentrations. When coupled with a mass spectrometry (MS) system, the probe electrospray ionization (PESI) method allows direct and rapid analysis of different types of matrices without pretreatment. In this study, we developed a PESI–MS method for the determination of MtF in plasma. We used a tandem mass spectrometer equipped with a PESI source in the reaction monitoring mode for the quantitation of MtF. MtF-d6 was chosen as the internal standard (IS), following an isotope dilution (ID) approach. The method was fully validated with six concentration levels (0.5–50 mg/L). The matrix effect was evaluated for each level, and the specificity was tested with a mix of potential co-medications. Using patient samples, the performance was compared with two classical LC–MS-MS and LC–diode array detector (DAD) methods used in external labs. Sample preparation consisted in mixing 10 µL plasma in 1, 000 µL ethanol/ammonium formate buffer including MtF-d6 at a fixed concentration of 5 mg/L. The total run time was 0.31 min. ID gave satisfactory results of accuracy and precision (min–max: −12.1 to 15.8% and 1.0–17.1%, respectively). The matrix effect was fully corrected by the internal standard (bias < 1%). The specificity study also reported satisfactory results. Finally, in a representative group of 29 patients (55% with a concentration <5 mg/L, 38% with a concentration >5 mg/L and 7% not detected), we observed almost identical results when comparing LC–DAD and LC–MS-MS to PESI–MS ( r 2 > 0.99). We propose a specific, sensitive, accurate and ultrafast solution for the measurement of MtF in patient plasma, with no sample preparation or calibration curve building. This could be helpful in a core lab when rapid diagnosis of LA is needed.