Detection Of Metformin Research Articles

Metformin as an Emerging Pollutant in the Aquatic Environment: Occurrence, Analysis, and Toxicity.

The use of human and veterinary drugs has led to the accumulation of pharmaceuticals in various aquatic environments at progressively increasing levels, exhibiting strong ecological risks. Metformin is widely used as a first-line prescription drug for the treatment of type 2 diabetes mellitus as well as a livestock drug. Unlike other drugs, metformin is not metabolized in the body, and almost all of its intake is excreted and released into the aquatic environment via urine and feces, causing adverse effects on aquatic ecosystems. This review provides an overview of the occurrence and detection of metformin in the aquatic environment and its toxic effects on different aquatic organisms (fish, daphnia, rotifers, chlorella). Metformin has been documented in a variety of aqueous environments such as wastewater, surface water, and groundwater as well as drinking water. The wide distribution of metformin in the aqueous environment calls for the development of more accurate detection methods. This paper reviews detection methods for metformin in the aqueous environment and evaluates their advantages and disadvantages. Toxicity studies have shown that metformin can cause adverse reactions in fish, such as oxidative stress, genotoxicity, disruption of intestinal flora, and morphological alterations; it also affects the growth and reproduction of small aquatic organisms. Knowledge gaps in the field of metformin research were assessed, and future research priorities were identified.

An electrochemical sensor based on synergistic enhancement effects between nitrogen-doped carbon nanotubes and copper ions for ultrasensitive determination of anti-diabetic metformin

Metformin (MET) is the primary medicine for type II diabetes, which produces carcinogenic byproducts during chlorine disinfection, so the detection of MET in aqueous environment is crucial. In this work, an electrochemical sensor based on nitrogen-doped carbon nanotubes (NCNT) has been constructed for ultrasensitive determination of MET in the presence of Cu(II) ions. The excellent conductivity and rich π-conjugated structure of NCNT facilitate the electron transfer rate of fabricated sensor and benefit the adsorption of cation ions. Cu(II) ions can chelate with MET to form MET-Cu(II) complex, which are easily accumulated on the surface of NCNT through cation-π interaction. Attributing to the synergistic enhancement effects of NCNT and Cu(II) ions, the fabricated sensor exhibits excellent analytical performances with a low detection limit of 9.6 nmol L−1, high sensitivity of 64.97 A mol−1 cm−2 and wide linear range of 0.3–10 μmol L−1. The sensing system has been successfully applied for rapid (20 s) and selective determination of MET in real water samples with satisfactory recoveries (90.2 %–108.8 %). This study provides a robust strategy for MET detection in aqueous environment and holds great promise for rapid risk assessment and early warning of MET.

Bariatric surgery and changes in metformin distribution: About a fatal case

Metformin is an hypoglycemic drug, represented as the « gold standard » for the treatment of maturity-onset diabetes. Lactic acidosis is a well known and feared adverse effect of this substance.The authors present the case of a 65 year-old woman, suffering from mellitus type 2 diabetes and obesity, who died at home, only three days after bariatric surgery (Roux-en-Y gastric by-pass, RYGB). Her treatment, including metformin and dapagliflozin, was stopped before surgery and not postoperatively resumed. The woman was visited by a friend 15 hours before the body discovery, and no information was available about the symptoms presented by the patient before the death, excepted asthenia. A forensic autopsy was performed. Cardiac and femoral blood, urine, gastric content and hair were collected for toxicological investigations. Metformin was specifically tested on a GC-MS/MS system. Liquid matrices (0.2 mL) were subject to protein precipitation with 3 mL of acetonitrile in the presence of merformin-d6 used as internal standard. After agitation and centrifugation, the surpernatant was evaporate to dryness and the dry extract was derivatized with MBTFA. Metformine was extracted from 20 mg of hair with methanol. Detection of metformin was achieved using two transitions: m/z 303 > 288 and m/z 303 > 125. No evidence of digestive perforation or peritonitis was identified during autopsy, excluding an early surgery complication as the cause of death. These findings were confirmed by the histological analysis which showed a physiological intestinal inflammatory reaction related to the recent surgery. Toxicological analysis revealed the presence of acetone in the blood (0.25 g/L) and in the urine (0.58 g/L), confirming diabetes. Metformin tested positive in blood (148 mg/L), urine (49 mg/L), intestinal content (> 100 mg/L) and hair (1.9 ng/mg). Blood concentration was considered potentially fatal. The low concentration in urine indicated rapid death after exposure. Hair concentration was in the therapeutic range. The pathologist concluded that the death was due to lactic acidosis caused by an overdose of metformin. With no evidence for suicide by ingestion of metformin, the hypothesis raised by the authors was that the bariatric surgery might have caused changes in the absorption of metformin, leading to a rapid overdose and death. In the literature, it has been demonstrated in gastric bypass patients that there is a significant increase in the bioavailability of metformin following oral administration. RYGB would increases intestinal transit time and thus the duration of exposure to small intestinal mucosa. Changes induced by the surgical procedure are probably not sufficient to explain the massive concentrations of metformin found in the postmortem samples but the context of the corpse discovery was not suggestive of suicide. As this represents the first case of metformin overdose following bariatric surgery, further cases will be needed to confirm our initial observations. It can be anticipated that a therapeutic dose can become toxic when administrated to a subject who recently modified her digestive equipment. This case highlights the doubts that can be encountered by pathologists and toxicologists in forensic medicine and that evidences must constantly be reconsidered.

Adsorption behavior of metformin drug on boron nitride fullerenes: Thermodynamics and DFT studies

In this study, a density functional theory (DFT) calculation was carried out for the adsorption behavior and detection of metformin on the exterior surfaces of pure and doped boron nitride (BN) fullerenes by using B3LYP-D and PW91-D functionals. The results demonstrate that the NH group of metformin can chemisorb on the boron atom of B12N12 and B16N16 fullerenes. Presence of polar solvent (water) increases the adsorption energy of metformin on the pure and GaB11N12 fullerenes. However, at the presence of Ga doping and it was found that the doping increases the binding energy of the metformin molecule, while the Ge doping decreases the binding energy. So our calculations suggest that the GeB11N12 has a greater sensitivity for the metformin molecule compared with the GaB11N12 fullerene. Our results represented that the GeB11N12 fullerene has good potential as a biosensor for the determination of metformin in environmental systems.

Detailed sorption characteristics of the anti-diabetic drug metformin and its transformation product guanylurea in agricultural soils

Detection of metformin, an antidiabetic drug and its transformation product guanylurea in various environmental matrices such as surface water and groundwater, coupled with their effects on aquatic organisms warrant an understanding of the compounds fate and behaviour in the environment. Batch studies were conducted with the aim of evaluating the sorption of these two emerging contaminants in six New Zealand agricultural soils of contrasting physico-chemical properties. Kinetic studies revealed that metformin and guanylurea sorption in Te Kowhai soil was very rapid initially achieving 90% sorption within the first 4 and 13h, respectively. Fit of several isotherm models to the measured batch sorption data showed that the hybrid models Langmuir-Freundlich and Redlich-Peterson best described the isotherms. Freundlich isotherm showed higher linearity for guanylurea (nF=0.58–0.93) in all soils compared to metformin (nF=0.25–0.71). A linear isotherm was fitted at environmentally relevant low concentrations (< 3mg/L) of target compounds and calculated values of sorption distribution coefficient (Kd) were in the range of 8.97 to 53.49L/kg for metformin and between 10.6 and 37.51L/kg for guanylurea. Sorption of both metformin and guanylurea was dependent on the soil characteristics, however, no generalisation could be made as to which had higher affinity to soils studied. Pearson's correlation and multiple regression analyses indicate that Si/Al (p=0.042) and clay (p=0.015) significantly influenced metformin Kd values, whereas the soil's cation exchange capacity (p=0.024) is the single most significant factor determining guanylurea sorption in soils. It is likely that the type of minerals present in soils and its ion-exchange capacity could play an important role in metformin and guanylurea sorption, respectively.

Occurrence of the antidiabetic drug Metformin and its ultimate transformation product Guanylurea in several compartments of the aquatic cycle

In 2030, the World Health Organization estimates that more than 350million people will be diagnosed with diabetes. Consequently, Metformin – the biguanide drug of choice orally administered for diabetes type II – is anticipated to see a spike in production.Unlike many pharmaceutical drugs, Metformin (Met) is not metabolized by humans but passes through the body unchanged. Entering aquatic compartments, such as in sewage, it can be bacterially transformed to the ultimate transformation product Guanylurea (Gua).Sampling over one week (n=5) from a Southern German sewage treatment plant revealed very high average (AV) concentrations in influent (AVMet=111,800ng/L, AVGua=1300ng/L) and effluent samples (AVMet=4800ng/L, AVGua=44,000ng/L).To provide a more complete picture of the distribution and potential persistence of these compounds in the German water cycle, a new, efficient and highly sensitive liquid chromatography mass spectrometric method with direct injection was used for the measurement of Metformin and Guanylurea in drinking, surface, sewage and seawater. Limits of quantification (LOQ) ranging from 2–10ng/L allowed the detection of Metformin and Guanylurea in different locations such as: Lake Constance (n=11: AVMet=102ng/L, AVGua=16ng/L), river Elbe (n=12: AVMet=472ng/L, AVGua=9ng/L), river Weser (n=6: AVMet=349ng/L, AVGua=137ng/L) and for the first time in marine North Sea water (n=14: AVMet=13ng/L, AVGua=11ng/L). Based on daily water discharges, Metformin loads of 15.2kg/d (Elbe) and 6.4kg/d (Weser) into the North Sea were calculated. Lake Constance is used to abstract potable water which is further purified to be used as drinking water. A first screening of two tap water samples contained 2ng/L and 61ng/L of Metformin, respectively. The results of this study suggest that Metformin and Guanylurea could be distributed over a large fraction of the world's potable water sources and oceans. With no natural degradation processes, these compounds can be easily reintroduced to humans as they enter the food chain.

Simultaneous Determination of Metformin, Nateglinide and Gliclazide in Pharmaceutical Preparations Using Micellar Liquid Chromatography

A micellar chromatographic method has been developed and validated for simultaneous separation and determination of metformin(MF), nateglinide (NT) and gliclazide (GL) . The separation was carried out using a Nucleosil C18 column, 150 mm × 4.6 mm i.d., 5 µm particle size, using micellar mobile phase consisting of sodium dodecyl sulphate (SDS), n-propanol with UV detection. The optimum conditions for the simultaneous separation of the three drugs were 0.12 M SDS, 10% (v/v) n-popanol, 0.3% triethylamine adjusted to pH5.6 with a flow rate of 1 ml.min-1 and detection at 254 nm. The limit of detection (LOD) of MF, NT, GL were 0.047, 0.00115, 0.036 µg.mL-1 respectively. The method showed good linearity in the ranges of 0.4-16 µg.mL-1, (r2=0.999), 0.8-16 μg.ml-1 (r2=0.999) and 1-40 μg.ml-1 (r2=0.999) for MF, NT, GL respectively. The suggested method was successfully applied for the analysis of the three antidiabetic drugs in pharmaceutical preparations with average recoveries of 99.66%, 100.08% and 100.31% for MT, NT and GL respectively. The results obtained were in good agreement with those obtained from comparison methods. The method was validated regarding accuracy and precision.