CE with direct sample injection for the determination of metformin in plasma for type 2 diabetic mellitus: An adequate alternative to HPLC

Abstract

We developed a simple and selective CE with UV detection at 233 nm for the analysis of metformin in plasma based on direct sample injection without any pretreatment. The sample was employed with an electrokinetic injection of 10 kV for 100 s. CE separation of metformin from biological matrix was performed at 25 degrees C using a BGE consisting of 25 mM Tris buffer at pH 4.0. The linear range of the CE method for the determination of metformin in plasma was over the range of 0.1-2.0 mug/mL; the LOD of the drug in plasma (S/N = 3; injection 10 kV, 100 s) was 30 ng/mL. Data by CE were compared with the results obtained by a validated HPLC method. CE assay of metformin exhibited a very good correlation (r(2 )= 1) with respect to HPLC. CE determination of metformin is a robust, sensitive, and reproducible method with the advantage over HPLC of being fast, without prior extraction, or precipitation of proteins, also enabling quick assessment of metformin for pharmacokinetic and clinical studies.

Metformin: A Prospective Alternative for the Treatment of Chronic Pain

“…Metformin is eliminated by glomerular filtration and tubular secretion. According to the clinical trials, the renal clearance of metformin is around 50 ml/h (Wei et al, 2009). Plasma concentrations of metformin decrease rapidly after intravenous administration (Graham et al, 2011).…”

“…Pharmacokinetic-pharmacodynamic modeling has shown a correlation between the time course of metformin concentrations in the portal vein and gut wall and hypoglycemic effect, instead of drug concentrations in liver ( Stepensky et al., 2002 ; Sun et al., 2011 ). The time to reach maximal plasma concentrations in human beings after metformin administration (T max ) is 1.5 to 2.7 h ( Caillé et al., 1993 ; Sambol et al., 1996 ; Wei et al., 2009 ; Zhang et al., 2014 ; McCreight et al., 2018 ), which follows a multiphasic pattern ( Graham et al., 2011 ), giving a peak plasma concentration (C max ) of 1.1 to 2.5 µg/ml ( Wei et al., 2009 ; Zhang et al., 2014 ; Dias et al., 2019 ), and a steady-state concentration range of 0.3 to 1.5 µg/ml (see Table 2 ). Plasma protein binding is negligible, and the drug is not metabolized ( Scheen, 1996 ).…”

Development of a capillary electrophoresis–mass spectrometry method for the analysis of metformin and its transformation product guanylurea in biota

“…With its high charge already at neutral pH, metformin is well amenable to CE as visible from the broad pH range used for its analysis which ranged from 2.5 [25] to 10 [39]. However, CE methods published so far mostly used background electrolytes incompatible with MS, e.g., phosphate buffers [23,25,29,38]. Exceptions are the non-aqueous BGE made of 5 mM NH 4 OAc in MeCN + 5% HOAc which was published by Lai and Feng [26] for CE-UV analysis of metformin in human plasma and the aqueous BGE consisting of 50 mM formic acid for CE-MS analysis of metformin in human serum.…”

“…CE was used to quantify metformin in tablets [23,24], plasma [25,26], and serum [27,28] and rarely in other biofluids like urine [28]. CE is often used with UV detection at wavelengths below 230 nm (as low as 195 nm) [22] sometimes with capacitively coupled contactless conductivity detection (C 4 D) and once with electrochemiluminescence (ECL) detection [29]. We are aware of only one publication on CE-MS analysis of metformin [27].…”

“…Limits of detection (LOD) covered a very broad range. CE-UV or CE-C 4 D often reached LODs in the mg/L range, sometimes upper μg/l range, sufficient for metformin analysis in tablets and often also in plasma (therapeutic concentrations are 0.1-1 mg/l [29]). Only with MS or ECL detection or with dedicated sample preparation, lower values were reached [24].…”