Development and Validation of a ZIF-8/rGO/MWCNTs-Modified Electrochemical Sensor for Serum Metformin Determination and Exploratory Clinical Correlation in Women with PCOS

Abstract

Metformin is an accepted treatment for polycystic ovary syndrome (PCOS), particularly in patients with insulin resistance (IR). The accurate determination of metformin in biological samples is crucial for quantifying drug exposure and future therapeutic drug monitoring. In this study, a ZIF-8/rGO/MWCNT-modified glassy carbon electrode (ZIF-8/rGO/MWCNTs/GCE) was developed for the detection of metformin in serum samples extracted from women with PCOS using electrochemical analysis. The modified electrode was obtained by stepwise drop-casting of the nanocomposite onto the GCE surface and was employed under optimized experimental conditions, including a phosphate buffer solution at pH 5.5, a ZIF-8:rGO:MWCNTs ratio of 2:1:1, a drying time of 40 min, and a scan rate of 100 mV/s. Under these conditions, the sensor showed a linear metformin response over the 2–28 µM concentration range, with a correlation coefficient of 0.99671. The limits of detection (LOD) and quantification (LOQ) were 0.14 µM and 0.42 µM, respectively. The recoveries ranged from 95.65% to 99.68%, indicating the suitability of the method for determining metformin in serum samples. This method was applied to serum samples from metformin-treated patients with PCOS, and variable and detectable levels of metformin were determined. The measured metformin concentrations were examined along with biochemical and hormonal variables. No direct associations were found between serum metformin levels and the clinical parameters assessed in this dataset in the exploratory correlation analysis. Overall, the proposed ZIF-8/rGO/MWCNTs/GCE sensor provides a convenient electrochemical platform for the detection of metformin in extracted serum samples.

Keywords: Metformin; Electrochemical sensor, ZIF-8/rGO/MWCNTs, human serum, polycystic ovary syndrome, therapeutic drug monitoring.