Gamma-cyclodextrin functionalized silver nanoparticle-based colorimetric assay for the determination of metformin in pharmaceutical samples

Metformin hydrochloride (MET) (N,N-dimethylbiguanide) is an antidiabetic drug and widely used for treating worldwide disease, Type 2 diabetes. MET shows significant benefits for human health such as reducing high blood sugar and cholesterol/triglyceride levels, treating for polycystic ovary syndrome and having anticancer and antiaging effects. In this study, a facile colorimetric determination of metformin in drug preparations was carried out by environmentally friendly gamma-cyclodextrin (γ-CD) stabilized silver nanoparticles (CD-AgNPs). Gamma-cyclodextrin was used for the formation of AgNPs as both the metal salt − reducing and nanoparticle − stabilizing agent. As a visual optical probe, well-dispersed spherical yellow-colored CD-AgNPs (at an average particle size of 10 ± 2 nm) showing maximal surface plasmon resonance absorption at 405 nm was synthesized by one-step method. In the presence of metformin, dispersed AgNPs get aggregated, and a controlled destabilization of CD-AgNPs and core-centered growth of Ag(0) atoms (20 ± 2 nm) were observed a result of host-guest interaction between CD-AgNPs and metformin. Non-covalent hydrogen bonding between the hydroxyl groups of CD-AgNPs (in the outer cavity) and the guanidine groups of MET enables the CDs to form a host-guest inclusion complexation followed by aggregation leading to color change from yellow to orange and an increase of the absorbance at 550 nm. Inclusion complex formation was characterized by using FTIR, UV-Vis spectroscopy, DSC and STEM techniques. Under optimized conditions, the absorbance ratio at A_{550 nm}/A_{405 nm} was linearly correlated to the concentration of metformin in the range of 0.2–1.25 µM. The proposed assay showed high sensitivity with 42 nM detection limit. The method was selective toward possible interferents (potassium, carbonate, sulfate, chloride and sodium ions, urea, glucose) and also successfully applied to conventional drug samples including MET. The results obtained by proposed, reference and HPLC assays were analyzed statistically using the two-way ANOVA test to demonstrate their agreement with each other at 95% confidence level (P = 0.05, F_exp = 0.068, F_crit(table) = 6.943, F_exp < F_crit(table)). MET contents (mg) of drug samples in tablet form were determined with high accuracy (REC% 97.3-100.7) and reproducibility (RSD% 1.49–2.78). It is noteworthy that the developed CD-AgNP − based colorimetric method seems to be of higher or comparable sensitivity compared to other nanoparticle − based optical assays.