Methimazole Concentrations Research Articles

Stability analysis of a mathematical model for methimazole dosing in graves' hyperthyroidism: A dynamic approach

This study explores a novel mathematical model for analyzing methimazole (MMI) therapy in patients with Graves' disease, a common autoimmune cause of hyperthyroidism. The model leverages a system of ordinary differential equations to capture the interplay between key factors: methimazole concentration, thyroid-stimulating hormone (TSH), free thyroxine (FT4) concentration, thyroid-stimulating hormone receptor antibody (TRAb) concentration, and functional thyroid gland size (V). Thirteen parameters account for the underlying physiological processes. Stability analysis were employedby Lyapunov stability theory and LaSalle's principle, to demonstrate the model's asymptotic stability. This implies the system converges towards a steady state under defined conditions. Additionally, a clinically relevant chart is constructed based on FT4 levels and treatment duration.For model validation, patient data is utilized within SimBiology simulations implemented in MATLAB. These simulations offer valuable insights into the dynamic response of hyperthyroidism to MMI treatment. This approach holds promise for future applications in optimizing treatment strategies and facilitating personalized medicine approaches.

Green emissive nitrogen-doped graphene quantum dots for fluorescence off–on probing methimazole via palladium (II) mediated assay

A palladium ion ([Formula: see text])-mediated nitrogen-doped graphene quantum dots (N-GQDs/Pd[Formula: see text]) was developed as a fluorescent “off–on” probe for methimazole (MZ). Fluorescent N-GQDs interact with Pd[Formula: see text] through coordination interactions, leading to weak photoluminescence (PL) owing to the quenching ability of Pd[Formula: see text]. Upon introducing MZ, the stronger binding between N-GQDs and Pd[Formula: see text] destroys the N-GQDs/Pd[Formula: see text] complex and restores the PL of N-GQDs. The probe exhibits a linear PL response to MZ concentrations from 3.0 to 50.0 [Formula: see text]M with a detection limit down to 4.5 nM. In addition, the probe has been used to detect MZ in real samples including natural water sources and human urine.

A Novel Enhanced-Fluorescent Probe Based on DHLA-Stabilized Red-Emitting Copper Nanoclusters for Methimazole Detection Via Aggregation-Induced Emission Effect.

Herein, an aqueous phase synthesis approach was presented for the fabrication of copper nanoclusters (Cu NCs) with aggregation-induced emission (AIE) property, utilizing lipoic acid and NaBH4 as ligands and reducing agent, respectively. The as-synthesized Cu NCs exhibit an average size of 3.0 ± 0.2nm and demonstrate strong solid-state fluorescence upon excitation with UV light. However, when dissolved in water, no observable fluorescent emission is detected in the aqueous solution of Cu NCs. Remarkably, the addition of Methimazole induced a significant red fluorescence from the aqueous solution of Cu NCs. This unexpected phenomenon can be ascribed to the aggregation of negatively charged Cu NCs caused by electrostatic interaction with positively charged imidazole groups in Methimazole, resulting in enhanced fluorescence through AIE mechanism. Therefore, there exists an excellent linear correlation between the fluorescent intensities of Cu NCs aqueous solution and the concentration of Methimazole within a range of 0.1-1.5 mM with a low limit of detection of 82.2 µM. Importantly, the designed enhanced-fluorescent nanoprobe based on Cu NCs exhibits satisfactory performance in assaying commercially available Methimazole tablets, demonstrating its exceptional sensitivity, reliability, and accuracy.

A Molecularly Imprinted Fluorescence Sensor Based on Upconversion-Nanoparticle-Grafted Covalent Organic Frameworks for Specific Detection of Methimazole

Rapid detection and sensitive analysis of MMZ is of great importance for food safety. Herein, a fluorescent molecularly imprinted sensor based on upconversion nanoparticles (UCNPs) grafted onto covalent organic frameworks (COFs) was designed for the detection of MMZ. COFs with a high specific surface area and excellent affinity serve as substrates for grafting of UCNPs, which can inhibit the aggregation burst of UCNPs and improve the mass transfer rate of the sensor. Through a series of characterizations, it was found that the proposed UCNP-grafted COFs@MIP-based sensor had good optical stability, high adsorption efficiency, strong anti-interference ability, and high sensitivity owing to the integration of the advantages of UCNPs, COFs and MIPs. Under the optimal conditions, a good linear relationship was presented between the fluorescence intensity of UCNP-grafted COFs@MIPs and the methimazole concentration in the range of 0.05–3 mg L−1, and the detection limit was 3 μg L−1. The as-prepared UCNP-grafted COFs@MIPs were successfully applied for the detection of MMZ in actual samples, and the results were relevant with those determined by high-performance liquid chromatography. The sensor has good sensitivity, reusability, and high selectivity, which are highly valuable in the rapid analysis and detection of food safety.

Protective Effect of Natural Antioxidant Compounds on Methimazole Induced Oxidative Stress in a Feline Kidney Epithelial Cell Line (CRFK).

The treatment of choice for feline hyperthyroidism is the administration of the antithyroid drug methimazole. Both the endocrinopathy and the drug adverse reactions (e.g., hepatotoxicosis, gastrointestinal disorders, and renal injury) are partly due to oxidative stress and redox unbalance. This study investigated the free radical production and the impairment of the antioxidant barrier induced by methimazole in an in vitro model of feline renal epithelium. The protective effects of quercetin and resveratrol were also explored. CRFK cells were incubated with a methimazole concentration equivalent to the maximum plasma levels in orally treated cats (4 µM), in the presence or absence of either one of the two selected antioxidants at different time-points (up to 72 h). Cell viability, ROS production, GSH levels, and mRNA expression of antioxidant enzymes (i.e., CAT, SOD, GPx, and GST) were assessed. Methimazole impaired cell viability and increased ROS levels in a time-dependent manner. Similarly, GSH content and CAT, SOD, and GPx3 expression were higher compared with control cells. Such effects were significantly counteracted by quercetin. These results provide new insights about the mechanisms underlying the methimazole-related side effects frequently observed in hyperthyroid cats. They also support the use of quercetin in the management of feline hyperthyroidism.

The Effect of Supporting Electrolyte Concentration on Zinc Electrodeposition Kinetics from Methimazole Solutions

AbstractThe kinetic parameters of Zn2+ ion electroreduction in sodium perchlorate used as the supporting electrolyte on the mercury electrode in the presence of methimazole were determined using electrochemical impedance spectroscopy (EIS), cyclic voltammetry (CV) and DC polarography. The two‐stage nature of this process was demonstrated. Both steps are catalysed by a methimazole. The size of the acceleration effect depends on the concentrations of methimazole and the supporting electrolyte. The acceleration of the electrode process involves the formation of active complexes between the depolarizer ions and methimazole on the electrode surface. These complexes facilitate the exchange of charge between the electrode and zinc ions during electroreduction process. The change of the hydrating sphere of the zinc ion is also important here. This in turn depends on its oxidation state and the concentration of the supporting electrolyte.

Simple, rapid, and sensitive electrochemical determination of antithyroid drug methimazole using a boron-doped diamond electrode

This paper aims a rapid, cheap, simple and modification-free electroanalytical methodology using a boron-doped diamond electrode pretreated anodically for the determination of antithyroid drug methimazole in pharmaceutical samples. The drug was irreversibly oxidized which was a diffusion-controlled process. Using square wave voltammetry, a linear response was obtained for methimazole determination in Britton–Robinson buffer (pH 5.0) at + 0.89 V (vs. Ag/AgCl). Linearity was found between the oxidation peak currents and the concentration of methimazole from 0.5 to 25.0 µg mL−1 (4.38 × 10−6–2.19 × 10−4 M) with a detection limit of 0.085 µg mL−1 (7.45 × 10−7 M). The proposed method was applied for the determination of methimazole in commercial tablet samples.

Spectrophotometric Determination of Methimazole by Silicomolybdenum Blue

Under optimum reaction conditions, Ammonium silicomolybdate could be quantitatively reduced to silicomolybdenum blue by hydrosulfuryl(-SH) in methimazole molecule, and the content of methimazole was determinated indirectly through determinating the absorbance of the silicomolybdenum blue. A novel method for the spectrophotometric determination of methimazole by silicomolybdenum blue has been established. The results showed that the maximum absorption wavelength of silicomolybdenum blue is 730 nm, good linear relationship is obtained between the absorbance of silicomolybdenum blue and the concentration of methimazole in the range of 8.000-160.0μg/mL, and the equation of the linear regression is A=0.0757+11.547ρ (mg/mL) with a linear correlation coefficient is 0.9998. This proposed method has been applied to determinate of methimazole in tablets, and the results agree well with those obtained by pharmacopoeial method.

Spectrophotometric Determination of Methimazole in Pharmaceutical Sample by Fe(II)-2,2’-Bipyridyl System

By controlling pH=5.0, Fe(III) could be reduced to Fe(II) by hydrosulfuryl (-SH) in methimazole molecule, then Fe(II) reacts with 2,2′-bipyridyl to form the orange red complex which the maximum absorption is at 522nm. The content of methimazole can be measured by measuring the amount of the complex of Fe(II)-2,2′-bipyridyl. A accurate fast spectrophotometric method for the determination the content of methimazole had been established. A good linear relationship was obtained between A and the concentration of methimazole in the range of 0.0004000-0.004000mg/mL, the equation of the linear regression was A=0.02707+136.29C(mg/mL), with a linear correlation coefficient was 0.9994. This proposed method had been successfully applied to determinate of methimazole in real pharmaceutical.

Ultra-trace detection of methimazole by surface-enhanced Raman spectroscopy using gold substrate

Gold nanoparticles (AuNPs) were set up by a reduction technique and fabricated as SERS substrates for methimazole detection, which is of therapeutic significance. The morphology of the nanoparticles were characeterized utilizing Fourier Transform Infrared Spectroscopy (FTIR), Transmission Electron Microscopy (TEM), UV–vis spectroscopy, Scanning Electron Microscopy (SEM) and Raman spectroscopy. The regular size of the AuNPs was around 10nm. The maximum absorbance for the UV–vis spectrum appeared at 524nm. Density Functional Theory (DFT) computations and surface Enhanced Raman Spectroscopy (SERS) were used to study to the adsorption behavior of methimazole on the AuNPs substrates. SERS experiment and DFT calculations suggested the possibility of molecular interactions between the AuNPs and methimazole. SERS experiment showed an improvement in the bands which was used to obtain a rectilinear relationship between the concentration of methimazole and the intensity of the SERS signal. AuNPs showed a good coefficient of correlation and improved limit of detection.

Silver nanoparticles for detection of methimazole by surface-enhanced Raman spectroscopy

An efficient method was developed for quantitative detection of methimazole using surface enhanced Raman spectroscopy (SERS). Silver nanoparticles (AgNPs) were prepared by a reduction method and designed as SERS substrates for the detection of methimazole, which is of medicinal importance. The morphology and the structure of the nanoparticles were characterized using a transmission electron microscope, a UV–vis spectroscopy, a Fourier transformed infrared spectroscopy and a Raman spectroscopy. The average size of the AgNPs was 60nm. The UV–vis spectrum showed a characteristic maximum absorbance at around 420nm for AgNPs. The adsorption behavior of methimazole on the AgNPs substrates was investigated by SERS and density functional theory (DFT) calculations. SERS experimental and theoretical results imply that a chemical interaction is considered between the NPs and methimazole. SERS experiments indicated an enhancement in the bands, which was utilized to develop a linear correlation between the methimazole concentrations and SERS signal intensity.

Fast Electrocatalytic Determination of Methimazole at an Activated Glassy Carbon Electrode.

A fast and simple voltammetric method for the determination of methimazole in pharmaceutical products was reported. A glassy carbon electrode was pretreated by anodization at +1.75 V (vs. SCE) for 5 min, followed by potential cycling in the range of 0.3-1.3 V (20 cycles). The pretreated electrode showed an excellent electrocatalytic effect on the oxidation of methimazole. Compared with untreated electrode, a large decrease (~300 mV) in the oxidation peak of methimazole was observed. The oxidation peak current at the new potential (0.4 V vs. SCE) was linearly dependent on the concentration of methimazole in the range of 7.0 - 130 μM with a detection limit of 3.7 μM (S/N = 3). The method was successfully used in the determination of methimazole in thyramozol tablets. Due to the simple and fast electrode preparation, there is no need for electrode cleaning or storage.

Paradoxical effect of methimazole on liver mitochondria: In vitro and in vivo

Methimazole is the most frequently prescribed antithyroid agent. On the other hand, several cases of liver injury are attributed to this drug. The mechanism of methimazole-induced liver injury is obscure. Hepatocytes mitochondria seem to be a target for methimazole cytotoxicity. Current investigation aimed to evaluate the effects of methimazole on the hepatocytes mitochondria in different experimental models. In the in vivo model, methimazole (100, 200 and 400mg/kg, i.p) was administered to mice and liver mitochondria were isolated and assessed. In the in vitro experiments, intact isolated liver mitochondria were incubated with increasing methimazole concentrations (10μM–100mM). It was found that methimazole decreased liver mitochondrial ATP and glutathione, increased mitochondrial swelling, lipid peroxidation and reactive oxygen species (ROS), and collapsed mitochondrial membrane potential when administered to mice. Paradoxically, methimazole not only caused no significant injury toward isolated liver mitochondria in vitro but improved mitochondrial function and protected this organelle. The differences between two investigated models in the current study might be associated with drug bioactivation and reactive metabolites formation. These findings suggest mitochondrial dysfunction as a mechanism for methimazole-induced liver injury. Moreover, methimazole seems to be a novel mitochondrial protecting agent in vitro.

Graphene Dendrimer-stabilized silver nanoparticles for detection of methimazole using Surface-enhanced Raman scattering with computational assignment.

Graphene functionalized with polyamidoamine dendrimer, decorated with silver nanoparticles (G-D-Ag), was synthesized and evaluated as a substrate with surface-enhanced Raman scattering (SERS) for methimazole (MTZ) detection. Sodium borohydride was used as a reducing agent to cultivate silver nanoparticles on the dendrimer. The obtained G-D-Ag was characterized by using UV-vis spectroscopy, scanning electron microscope (SEM), high-resolution transmission electron microscope (TEM), Fourier-transformed infrared (FT-IR) and Raman spectroscopy. The SEM image indicated the successful formation of the G-D-Ag. The behavior of MTZ on the G-D-Ag as a reliable and robust substrate was investigated by SERS, which indicated mostly a chemical interaction between G-D-Ag and MTZ. The bands of the MTZ normal spectra at 1538, 1463, 1342, 1278, 1156, 1092, 1016, 600, 525 and 410 cm−1 were enhanced due to the SERS effect. Correlations between the logarithmical scale of MTZ concentrations and SERS signal intensities were established, and a low detection limit of 1.43 × 10−12 M was successfully obtained. The density functional theory (DFT) approach was utilized to provide reliable assignment of the key Raman bands.

Regional variations in percutaneous absorption of methimazole: an invitro study on cat skin.

The use of transdermal gel medications in cats has become popular in veterinary medicine due to the ease of administration compared to oral medication. The research to support systemic absorption of drugs after transdermal gel administration and the preferred skin region to apply these drugs in cats is limited. The aim of this study was to characterize the effect of different skin regions on the percutaneous absorption pharmacokinetics of a commercially available transdermal methimazole after a finite dose was applied to feline skin invitro. A commercial formulation of methimazole (10mg) was applied to four skin regions (the inner stratum corneum of the ear, groin, neck, and thorax regions) from six cats. The receptor medium was sampled up to 36h postapplication, and methimazole concentrations were measured using high-performance liquid chromatography. Methimazole was absorbed more completely across the pinnal skin, compared to the groin, neck, and thorax (P<0.001), which justifies application to the pinna to maximize efficacy and also to minimize the effects of grooming.

Percutaneous absorption of methimazole: an in vitro study of the absorption pharmacokinetics for two different vehicles

The use of transdermal medications in cats has become popular in veterinary medicine due to the ease of administration compared to oral medication. However, the research to support systemic absorption of drugs applied to the pinna after transdermal administration in cats is limited. The aim of this study was to characterize the percutaneous absorption pharmacokinetics of methimazole in a lipophilic vehicle compared to methimazole in Pluronic(®) lecithin organogel (PLO) using a finite dose applied to feline ear skin in an in vitro Franz cell model. The two formulations of methimazole (10mg) were applied to the inner stratum corneum of six pairs of feline ears. The receptor medium was sampled up to 30h post-administration, and methimazole concentrations were measured using high-performance liquid chromatography (HPLC). Histological examination of all ears was undertaken as small differences in the thickness of ear skin may have contributed to inter-individual differences in methimazole absorption between six cats. Methimazole was absorbed more completely across the pinnal skin when administered in the lipophilic vehicle compared to administration in the PLO gel (P<0.001).

Trans-pinnal movement of methimazole: an in vitro study showing that methimazole can cross from the inner to outer pinna of cats.

The aim of the study was to determine if methimazole applied in a transdermal formulation to the internal pinna will cross to the external pinna in an in vitro Franz cell model. The ears from six cats were harvested soon after death. Whole ears were mounted onto Franz-type diffusion cells with the stratum corneum of the inner pinnae uppermost. A commercial transdermal preparation containing methimazole (0.1 ml/10 mg) was applied to the inner pinnae. At 1, 2, 4, 6, 8, 12, 18, 24 and 30 h, a 200 µl sample of reservoir solution was removed to determine the methimazole concentration by high-performance liquid chromatography. The ears were then dissected, separating the internal pinna from the cartilage and the external pinna, before the methimazole concentration was measured at each site. The thickness of the different regions of the ear was measured on paraffin histology sections. Mean ± SD methimazole concentrations at 30 h for the right and left ear, respectively, were: inner ear, 1.25 ± 0.53 mg/g, 0.39 ± 0.26 mg/g; cartilage, 1.36 ± 0.47 mg/g, 0.33 ± 0.20 mg/g; and outer ear, 1.0 ± 0.32 mg/g, 0.33 ± 0.14 mg/g. There was a difference between the left and right ears (P <0.001). Minimal methimazole concentrations were detected in the receptor fluid. The mean methimazole concentration absorbed by the skin after application of 10 mg was, for the right ear, 3.65 ± 1.27 mg/g and, for the left, 1.08 ± 0.27 mg/g. There was no correlation between methimazole concentrations and thickness of each region of the ear. Methimazole in a lipophilic vehicle applied to the inner pinna will penetrate to the outer pinna of cats in an in vitro model, which may have safety implications for humans associated with cats treated with transdermal methimazole. Substantial inter-individual variation was found. Further research is required in the area of transdermal penetration of drugs in cats.

Sensitive amperometric determination of methimazole based on the electrocatalytic effect of rutin/multi-walled carbon nanotube film

Electrochemical deposition was used to prepare a glassy carbon electrode modified with multi-walled carbon nanotubes and the glycosidic compound, rutin (R/MWCNTs/GCE). Cyclic voltammetry of the modified electrode in aqueous solution (pH8) showed a pair of well-defined, stable and reversible redox peaks with surface confined characteristics. The catechol moiety of rutin produced the voltammetric peaks via a 2 electron, 2 proton mechanism in the range of 0.0–0.4V (vs. Ag/AgCl). The transfer coefficient (α), heterogeneous electron transfer rate constant (ks), and surface concentration (Γ) for R/MWCNTs/GCE were calculated by using the cyclic voltammetric data. The modified electrode showed excellent catalytic activity toward oxidation of methimazole. Fixed-potential amperometry was used for sub-micromolar determination of methimazole at pH8. Linear dependence of anodic current to methimazole concentration was obtained in the range of 0.1–26μM of the drug with a limit of detection at 18nM. The modified electrode retained its initial response for at least 2weeks if stored in dry ambient conditions. The electrode was used for the amperometric determination of methimazole in formulations and spiked blood serum samples, successfully.

Sensitive turn-on fluorescence assay of methimazole based on the fluorescence resonance energy transfer between acridine orange and silver nanoparticles

A new method for highly sensitive detection of methimazole was developed based on the fluorescence resonance energy transfer (FRET) between acridine orange (AO) and silver nanoparticles (AgNPs), in which AO acts as a donor and AgNP as an acceptor. The fluorescence of AO molecules was severely quenched when they were attached to the surface of AgNP by electrostatic attraction. Upon the addition of methimazole, AO molecules were detached from NPs because of strong adsorption of methimazole on the surface of AgNPs. Under optimum conditions, the enhanced fluorescence intensity displayed a linear relationship with the concentration of methimazole in the range of 8.0×10−9–3.75×10−7M, with a limit of detection of 5.5nM. The method was applied for the determination of therapeutic levels of methimazole in human plasma samples with satisfactory results.

A new Methimazole sensor based on nanocomposite of CdS NPs–RGO/IL–carbon paste electrode using differential FFT continuous linear sweep voltammetry

A Methimazole sensor was designed and constructed based on nanocomposite of carbon, ionic liquid, reduced graphene oxide (RGO) and CdS nanoparticles. The sensor signal was obtained by Differential FFT continuous linear sweep voltammetry (DFFTCLSV) technique. The potential waveform contains two sections, preconcentration potential and potential ramp. In this detection technique, after subtracting the background current from noise, the electrode response was calculated, based on partial and total charge exchanges at the electrode surface. The combination of RGO and CdS nanoparticles can catalyze the electron transfer, which outcomes of the amplification of the sensor signal. The result showed that the sensor response was proportional to the concentrations of Methimazole in the range of 2.0 to 300nM, with a detection limit of 5.5×10−10M. The sensor showed good reproducibility, long-term of usage stability and accuracy. The characterization of the sensor surface was studied by atomic force Microscopy and Electrochemical Impedance Spectroscopy. Moreover, the proposed sensor exhibited good accuracy, and R.S.D value of 2.82%, and the response time of less than 7s.