The Methods of Analysis for Determination of Metformin and Glimepiride in Different Matrices

In this literature review, we will introduce pharmacology in addition to most of the up-to-date reported methods that have been developed for determination of important oral hypoglycemic drugs which are metformin and glimepiride in their pure forms, combined forms with other drugs, combined forms with degradation products, and in biological samples.


Introduction
Diabetes mellitus is characterized by abnormally high levels of sugar (glucose) in the blood, When the amount of glucose in the blood increases, e.g., after a meal, it triggers the release of the hormone insulin from the pancreas. Insulin stimulates muscle and fat cells to remove glucose from the blood and stimulates the liver to metabolize glucose, causing the blood sugar level to decrease to normal level. In people with diabetes, blood sugar levels remain high. This may be because insulin is not being produced at all, or is not made at sufficient levels, or is not as effective as it should be. The most common forms of diabetes are type-1 diabetes (5%), which is an autoimmune disorder, and type 2 diabetes (95%), which is associated with obesity. Gestational diabetes is a form of diabetes that occurs in pregnancy, and other forms of diabetes are very rare and are caused by a single gene mutation [1].
Metformin (MTF, as seen in Figure 1), sold under the brand name Glucophage, among others, is the first-line medication for the treatment of type 2 diabetes. MTF is an antihyperglycemic agent that improves glucose tolerance in patients with type 2 diabetes, lowering both basal and postprandial plasma glucose. Its pharmacologic mechanisms of action are different from other classes of oral antihyperglycemic agents. MTF decreases hepatic glucose J Nanotechnol Nanomaterials. 2023 Volume 4, Issue 1 2 production, decreases intestinal absorption of glucose, and improves insulin sensitivity by increasing peripheral glucose uptake and utilization. MTF does not produce hypoglycemia in either patients with type 2 diabetes or normal subjects and does not cause hyperinsulinemia. With MTF therapy, insulin secretion remains unchanged while fasting insulin levels and daylong plasma insulin response may decrease [2][3][4].
Glimepiride (GLM, as depicted in Figure 1) is indicated for the management of type 2 diabetes in adults as an adjunct to diet and exercise to improve glycemic control as monotherapy. It may also be indicated for use in combination with metformin or insulin to lower blood glucose in patients with type 2 diabetes whose high blood sugar levels cannot be controlled by diet and exercise in conjunction with an oral hypoglycemic (a drug used to lower blood sugar levels) agent alone [5].
Its mechanism of action is based on ATP-sensitive potassium channels on pancreatic beta cells that are gated by intracellular ATP and ADP. The hetero-octomeric complex of the channel is composed of four pore-forming Kir6.2 subunits and 4 regulatory sulfonylurea receptor (SUR) subunits. Alternative splicing allows the formation of channels composed of varying subunit isoforms expressed at different concentrations in different tissues [7]. In pancreatic beta cells, ATP-sensitive K channels play a role as essential metabolic sensors and regulators that couple membrane excitability with glucose-stimulated insulin secretion (GSIS). When there is a decrease in the ATP:ADP ratio, the channels are activated and open, leading to K+ efflux from the cell, membrane hyperpolarization, and suppression of insulin secretion. In contrast, increased uptake of glucose into the cell leads to elevated intracellular ATP:ADP ratio, leading to the closure of channels and membrane depolarization. Depolarization leads to activation and opening of the voltage-dependent Ca 2+ channels and consequently an influx of calcium ions into the cell. Elevated intracellular calcium levels cause the contraction of the filaments of actomyosin responsible for the exocytosis of insulin granules stored in vesicles [3]. GLM blocks the ATPsensitive potassium channel by binding non-specifically to the B sites of both sulfonylurea receptor-1 (SUR1) and sulfonylurea receptor-2A (SUR2A) subunits as well as the A site of SUR1 subunit of the channel to promote insulin secretion from the beta cell [6].

Review of Analytical Methods
Various techniques were used for the analysis of MTF and GLM in its pure forms, in pharmaceutical formulations and in biological fluids. The available reported methods in the literature can be summarized as follows: