Sotalol Research Articles

Solid-liquid equilibrium and distribution in pharmaceutically relevant media of cardiovascular sotalol hydrochloride

The shake-flask method was used to determine the solubility of sotalol hydrochloride (STL), a cardiovascular drug, in solvents modeling a variety of body media within the temperature range (293.15–313.15) K. In the descending order of the drug solubility the solvents can be arranged as follows: buffer pH 2.0, buffer pH 7.4, 1-octanol, n-hexane. The experimental values of solubility of the drug in aqueous solvents agree well with the calculated values of the pH-solubility profile. The study shows that the maximum solubility of the salt is observed within the pH range from 2.9 to pHmax equal to 6.1. Temperature dependencies of the STL distribution coefficients were obtained in 1-octanol/buffer pH 7.4 and n-hexane/buffer pH 7.4 systems. Since the values of the partition coefficients of hydrophilic STL are low, it was concluded that the diffusion through the lipid biolayer of cell membranes was unfavorable and that the paracellular transport of the drug molecules might prevail. The thermodynamic functions of dissolution and transfer were calculated and discussed taking into account the physicochemical properties of STL and the solvents used.

An affordable and green voltammetric approach for the determination of sotalol in biological, environmental, and pharmaceutical samples

AbstractThis work outlines the development of a voltammetric method for a sensitive, rapid, and environmentally friendly determination of the antihypertensive sotalol (SOT) in several sample types employing the anodically pretreated boron‐doped diamond electrode. Cyclic voltammograms of SOT presented a well‐defined irreversible oxidation peak at 1.21 V (Ag/AgCl (3.0 mol L−1 KCl)) in Britton–Robinson buffer solution (pH 3.0). Figures of merits recommended by the validation guidelines were evaluated for the validation of the present method. Employing differential pulse voltammetry linearity of SOT was obtained in the concentration range of 0.39–4.22 μmol L−1 in 0.1 mol L−1 H2SO4 solution, with a limit of detection of 0.031 μmol L−1. The selectivity of the method was assessed against interferers and show relative standard deviation (RSD) values lower than 6 %. Recovery tests yielded percentages ranging from 93 % to 96 % in urine sample and from 100 % to 107 % in tap water sample. The proposed method was successfully applied in pharmaceutical, environmental, and biological samples offering a suitable green analytical chemistry profile.

HPLC and LC-MS/MS-Based Quantitative Characterization of Related Substances Associated with Sotalol Hydrochloride.

In total, three related substances (RS) associated with sotalol hydrochloride (STHCl) were herein identified with a novel gradient high-performance liquid chromatography (HPLC) protocol. Further characterization of these substances was then performed via liquid chromatography-mass spectroscopy (LC-MS/MS) and nuclear magnetic resonance (NMR) approaches. For these analyses, commercial STHCl samples were used for quantitative HPLC studies and the degradation of STHCl under acidic (1M HCl), alkaline (1M NaOH), oxidative (30% H2O2), photolytic (4500 Lx), and thermal stress conditions (100 °C) was assessed. This approach revealed this drug to be resistant to acidic, alkaline, and high-temperature conditions, whereas it was susceptible to light and oxidation as confirmed through long-term experiments. The putative mechanisms governing RS formation were also explored, revealing that RS3 was derived from the manufacturing process, whereas RS2 was generated via oxidation and RS1 was generated in response to light exposure. The cytotoxicity of these RS compounds was then assessed using MTT assays and acute toxicity test. Overall, this study provides details regarding the characterization, isolation, quantification, and toxicological evaluation of STHCl and associated RS compounds together with details regarding the precise, specific, and reliable novel HPLC technique, thus providing the requisite information necessary to ensure STHCl purity and safety.

Single- and multiple-dose pharmacokinetics of sotalol hydrochloride in healthy cats

Introduction/objectivesThe objective of this study was to describe the single- and multiple-dose pharmacokinetics and urinary elimination of sotalol in healthy cats. AnimalsSix adult purpose-bred cats Materials and methodsCats were administered 2 mg sotalol/kg body weight as a single intravenous bolus and as a single oral dose in a randomized crossover study with a two-week washout period. The same cats then received 3 mg sotalol/kg orally every 12 h for two weeks. Blood samples were collected at predetermined time points for 48 h postdose for quantification of sotalol using ultra-high-pressure liquid chromatography with mass spectrometry. Non-compartmental analysis was used to obtain pharmacokinetic parameters. Data are presented as median (min–max). ResultsFollowing intravenous administration, plasma clearance and volume of distribution were 9.22 mL/min/kg (5.69–10.89 mL/min/kg) and 2175.56 mL/kg (1961–2341.57 mL/kg), respectively. Bioavailability was 88.41% (62.75–130.29) following a single oral dose. Peak plasma concentration (Cmax) and time to Cmax were 0.94 μg/mL (0.45–1.17 μg/mL) and 1.5 h (0.5–4 h) after a single oral dose (2 mg/kg), and 2.29 μg/mL (1.91–2.48 μg/mL) and 1.0 h (0.5–1.5 h) with chronic oral dosing (3 mg/kg), respectively. Elimination half-life was 2.75 h (2.52–4.10 h) and 4.29 h (3.33–5.53 h) for single and chronic oral dosing, respectively. Accumulation index was 1.17 (1.09–1.29) after chronic dosing. Urinary sotalol recovery was 81–108% of the intravenous dose. ConclusionsOral sotalol administration resulted in plasma concentrations reportedly efficacious in other species, with good to excellent oral bioavailability. Urinary excretion appears to be a major route of elimination. Following repeated oral dosing, minimal drug accumulation was estimated. Additional studies in cats are recommended due to the possibility of nonlinear kinetics.

Efficacy and safety of dofetilide and sotalol in patients with hypertrophic cardiomyopathy

BackgroundProfessional society practice guidelines conflict regarding their recommendations of dofetilide (DOF) and sotalol (STL) for treatment of arrhythmias in hypertrophic cardiomyopathy (HCM), and supporting data is sparse. We aim to assess safety and efficacy of DOF and STL on arrhythmias in HCM.MethodsThis was an observational study of HCM patients treated with DOF or STL for atrial fibrillation (AF) and ventricular arrhythmias (VA). Outcomes of drug discontinuation and arrhythmia recurrence were compared at 1 year and latest follow-up by Kaplan–Meier analysis. Predictors of drug failure were studied using uni- and multi-variable analyses. Drug-related adverse events were quantitated.ResultsHere we show that of our cohort of 72 patients (54 ± 14 years old, 75% male), 21 were prescribed DOF for AF, 52 STL for AF, and 18 STL for VA. At 1 year, discontinuation and recurrence rates were similar for DOF-AF (38% and 43%) and STL-AF (29% and 44%) groups. Efficacy data was similar at long-term follow-up of 1603 (IQR 994–4131) days, and for STL-VA. Drug inefficacy was the most common reason for discontinuation (28%) followed by side-effects (13%). Incidences of heart failure hospitalization (5%) and mortality (3%) were low. One STL-AF patient developed non-sustained torsades de pointes in the setting of severe pneumonia and acute kidney injury, but there were no other drug-related serious adverse events.ConclusionsDOF and STL demonstrate modest efficacy and satisfactory safety when used for AF and VA in HCM patients.

Uptake and Enantiomeric Selectivity of β-Blockers in Lettuce (Lactuca sativa L.) and Tomato (Lycopersicon esculentum M.) in Soil-Pot Culture.

The uptake and translocation of β-blockers in lettuce (Lactuca sativa L.) and tomato (Lycopersicon esculentum M.) were investigated by carrying out a 70-day soil-pot cultivation. The root uptake parameters of β-blockers in lettuce decreased in the order of atenolol (ATE) > sotalol (SOT) > propranolol (PRO) with root bioconcentration factors (BCFsroot/soil) of 0.158, 0.136, and 0.096, respectively, which were positively correlated with their water solubility. The BCFroot/soil of β-blockers in tomato was higher than those in lettuce. ATE and PRO were prone to migrate to the aerial parts of tomato with translocation factors of 3.31 and 4.11, respectively. In tomato fruits, the enantiomeric profile of PRO and ATE shifted to that dominated by the more toxic enantiomer, i.e., (S)-PRO and (R)-ATE. The enantiomeric selectivity of β-blockers in the edible parts of lettuce and tomato indicated the potential ecotoxicity of these pharmaceuticals for plants and the human exposure risk via vegetable intake.

Combining Constructed Wetlands and UV Photolysis for the Advanced Removal of Organic Matter, Nitrogen, and Emerging Pollutants from Wastewater

This study reports the performance of a three-step lab-scale system including a hybrid digester (HD), a vertical flow (VF) constructed wetland, and a photodegradation (PD) lamp, with two different arrangements regarding the position of the recirculation point. In addition to total suspended solids (TSS), chemical oxygen demand (COD), and nitrogen compounds, removal of the following pollutants was investigated: paracetamol (ACE), ofloxacin (OFL), caffeine (CAF), ketoprofen (KET), ibuprofen (IBU), clofibric acid (ACB), bisphenol A (BPA), and sotalol (SOT). An excellent performance of HD was achieved on the elimination of TSS (82.2 ± 18.5% on average) and COD (63.9 ± 4.1%). TSS and COD removal increased to 91.2 ± 0.4% and 83.4 ± 2.9%, respectively, for the combined HD–VF system. Ammonia removal was 57.0 ± 7.8% in the VF unit while significant denitrification occurred in the HD. The overall HD–VF–PD system achieved mean removals of 100% for OFL, KET, SOT, and IBU, 98 ± 2% for ACE, 87 ± 8% for CAF, 81 ± 38% for ACB and 26 ± 9% for BPA. The removal of ACE, OFL, CAF, and IBU was mostly by biodegradation in the HD and VF units while the PD unit was responsible for the removal of KET, ACB, and SOT.

Abstract 12010: Efficacy and Safety of Dofetilide and Sotalol in Patients With Hypertrophic Cardiomyopathy

Introduction: Patients with hypertrophic cardiomyopathy (HCM) often have atrial fibrillation (AF) and ventricular arrhythmias (VA) requiring rhythm control. In the 2014 AF Guidelines, class III anti-arrhythmic drugs are not recommended in patients with left ventricular hypertrophy, but in the 2020 HCM Guidelines, sotalol (STL) and dofetilide (DOF) are deemed “reasonable” for rhythm control, both based on limited data. Methods: We conducted an observational study (2001-2021) of patients with HCM who were treated with DOF or STL for AF and/or VA. Baseline characteristics and drug-related adverse events were analyzed from the electronic medical record, and rates of discontinuation and arrhythmia recurrence at 1 year and by time of chart review were compared using Kaplan Meier curves and log rank test. Results: There were 21 DOF and 52 STL HCM patients with AF, and 18 STL patients with VA. At 1 year, AF patients on DOF or STL had no significant difference in rates of AF recurrence (42.9% vs 44.2%, p=0.664) or drug discontinuation (38.1% vs 29.4%, p=0.582). Recurrence and discontinuation rates of VA on STL were comparable (Figure). Over a median follow up of 1603 days (IQR 994, 4131), there was a trend toward greater efficacy for STL with respect to less AF recurrence (p=0.085) and less frequent discontinuation (p=0.153; Figure). On univariate analysis, only NYHA class predicted AF recurrence. Reasons for discontinuation were most often for inefficacy or mild side-effects. One patient with prior alcohol septal ablation who was on STL for AF developed complete heart block followed by non-sustained torsades de pointes in the setting of a severe influenza infection and later underwent defibrillator implantation. There were no other cases of pro-arrhythmia or sudden death related to DOF. Conclusions: DOF and STL are modestly effective for the treatment of AF and VA in HCM patients, with a low rate of serious adverse events.

The Potential of Constructed Wetland Systems and Photodegradation Processes for the Removal of Emerging Contaminants—A Review

The presence of emerging organic contaminants (EOCs) in the environment is increasing and requires the development of technologies for their effective removal. Therefore, a literature review on the behavior of EOCs during municipal wastewater treatment, both in major treatment systems and particularly in constructed wetlands (CWs), was carried out. The study also reviewed the behavior of EOCs in anaerobic digesters (ADs) and advanced oxidation processes, particularly in TiO2-based photocatalysis, which are being proposed as promising pre- and post-treatments for combination with CW. The following ten compounds were screened: acetaminophen (ACE), ofloxacin (OFL), caffeine (CAF), carbamazepine (CBZ), ketoprofen (KET), ibuprofen (IBU), diclofenac (DCL), clofibric acid (ACB), bisphenol A (BPA), and sotalol (SOT). The degradation pathways of the selected EOCs are largely influenced by their physicochemical and biochemical properties. Sorption and biodegradation are the main elimination mechanisms found in AD and CW treatment systems, where the combination of anaerobic and aerobic environments improves the elimination efficiency of EOCs. However, various contaminants appear recalcitrant. In this sense, in combination with CWs, TiO2-based photocatalysis emerges as a promising post-treatment for advanced EOC removal from wastewater.

Removal of emerging pollutants by a 3-step system: Hybrid digester, vertical flow constructed wetland and photodegradation post-treatments

The removal of emerging pollutants from municipal wastewater was studied for the first time using a three-step pilot-scale system: 1) hybrid digester (HD) as first step, 2) subsurface vertical flow constructed wetland (VF) as second step, and 3) photodegradation (PD) unit as third step or post-treatment. The HD and VF units were built and operated in series with effluent recirculation at pilot scale. For the PD post-treatment, three alternatives were studied at lab-scale, i) UVC irradiation at 254 nm (0.5 h exposure time), ii) UVA irradiation at 365 nm using a TiO2-based photocatalyst and iii) sunlight irradiation using a TiO2-based photocatalyst, the last two for 1 and 2 h. Alternative iii) was also tested at pilot-scale. Degradation of nine compounds was evaluated: acetaminophen (ACE), caffeine (CAF), carbamazepine (CBZ), ketoprofen (KET), ibuprofen (IBU), diclofenac (DCL), clofibric acid (ACB), bisphenol A (BPA), and sotalol (SOT). Overall, the HD-VF-UVC system completely removed (>99.5 %) ACE, CAF, KET, IBU, DCL and ACB, and to a lesser extent SOT (98 %), BPA (83 %) and CBZ (51 %). On the other hand, the HD-VF-UVA/TiO2 system (at 2 h) achieved >99.5 % removal of ACE, CAF, KET, IBU and DCL while ACB, BPA, CBZ and SOT were degraded by 83 %, 81 %, 78 % and 68 %, respectively. Working also at 2 h of exposure time, in summer conditions, the HD-VF-Sol/TiO2 system achieved >99.5 % removal of ACE, CAF, KET, IBU, DCL and ACB, and to a minor extent BPA (80 %), SOT (74 %) and CBZ (69 %). Similar results, although slightly lower for SOT (60 %) and CBZ (59 %), were obtained in the pilot sunlight plus TiO2 catalyst unit. However, the use of sunlight irradiation with a TiO2-based photocatalyst clearly showed lower removal efficiency in autumn conditions (i.e., 47 % SOT, 31 % CBZ).

Mechanism of bicarbonate enhancing the photodegradation of β-blockers in natural waters

The impact of HCO3− on the photodegradation of β-blockers was investigated under simulated sunlight irradiation. The results show that in the presence of HCO3−, the photodegradation rates increase significantly for sotalol (SOT), whereas no effects on the degradation of carvedilol and arotinolol are observed. Using quenching experiments, electron paramagnetic resonance spectra and degradation product determination, we demonstrate that carbonate radical (CO3•−) is formed by direct oxidation of HCO3− by triplet-excited SOT (3SOT*) and plays a significant role in SOT photodegradation. Competition kinetics experiments show that the three β-blockers all have high second-order rate constants (107–108 M−1 s−1) for the reaction with CO3•−. However, only 3SOT* has a higher reduction potential that can oxidize HCO3− to produce CO3•−. Thus, enhanced SOT removal rates in the presence of HCO3− were observed. In addition, the results show that seawater DOM could increase HCO3−-induced photodegradation of SOT, whereas SRNOM mainly behaves as a CO3•− quencher and decreases the removal rate of SOT. The results underscore the role of HCO3− in limiting the persistence of organic pollutants like SOT in sunlit natural waters, and especially in marine and coastal waters.

Abstract 16802: Economics and Outcomes of Sotalol and Dofetilide In-Patient Dosing Approaches in Patients With Atrial Fibrillation

Background: Inpatient initiation of sotalol (STL) and dofetilide (DFL) for patients with symptomatic atrial fibrillation (AF) can be variable, more so for STL. Objective: Define the impact of inpatient initiation of STL and DFL approaches on patient in-hospital costs and outcomes. Methods: AF patients that were admitted for STL (n=133) or DFL (n=38) initiation at an Intermountain Healthcare Hospital in 2018 were included to provide contemporary insight. Patient and dosing characteristics were described descriptively, and the impact of dosing schedule was correlated with daily hospital costs and outcomes. The CMS reimbursement for 3-day initiation of STL or DFL is $9,263.51. Results: The average age of the complete population was 69.7±11.7 years and 64.3% were male. Baseline risk factors were similar between groups. Mean ejection fraction was 59.2±8.9% and median QTc was 455.7±38.5 ms before STL dosing and 453.7±37.6 before DFL dosing. The average length of stay was 3.7±4.2 days and was shorter for DFL (3.0±2.0) compared to the STL (3.9±4.6). Within the DFL group, most received 5-6 doses, whereas STL dosing frequency was variable (Figure A). DFL discharge dose in 22 (57%) was 500 mcg BID and 125 mcg BID in 8 (21%). STL dose was 80 mg BID in 96 (72.1%) and 40 mg BID in 29 (21.8%). Total costs per hospitalization and per day were higher for STL compared to DFL (Figure B). QTc prolongation >500 ms was more common with DFL versus STL and other long-term outcomes were similar (Figure C). A 24 load of IV sotalol result in a cost savings of $871.55 vs. a 2-day load and $3,803.10 vs. a 3-day oral load. Conclusion: Routine contemporary inpatient STL dosing is markedly variable and results in the potential of both cost gain and loss to a hospital. Under dosing of STL is also common and may negatively impact long-term outcomes.

Effects of Anisodine Hydrobromide on the Cardiovascular and Respiratory Functions in Conscious Dogs.

PurposeAnisodine hydrobromide (Ani) is isolated from the medicinal plant Anisodus tanguticus (Maxim.) Pascher for clinical use. Although considerable research regarding Ani has been reported, the safety profiles of Ani are currently unknown. This study investigated the cardiorespiratory effects of Ani in conscious dogs to provide clinicians a detailed safety profile of Ani on the cardiorespiratory system.Materials and MethodsUsing the Latin square design, the study was divided into six phases, where in each phase, six telemetered beagle dogs received one dose of normal saline or sotalol hydrochloride or Ani (0.1, 0.4, 1.6, or 6.4 mg/kg). Electrocardiogram, blood pressure (BP) and respiratory parameters were collected before and after administration for 24 hours. Statistical comparisons were performed at scheduled time-points.ResultsThe heart rate was significantly increased, PR and QTCV intervals were significantly shortened in Ani 0.4, 1.6, 6.4 mg/kg treatment group after drug administration. Compared with the saline group, a significant increase in heart rate and shortening of PR, QTCV intervals were observed in the Ani 1.6, 6.4 mg/kg treatment groups from 5 min to 4 h time-points. Diastolic and mean BP were significantly increased in Ani 1.6, 6.4 mg/kg from 1 h to 2 h time-points compared to those of the saline control. Accelerated breathing was observed in the first 20 min after Ani 0.4, 1.6, and 6.4 mg/kg treatment, although not statistically significant. Furthermore, no significant differences were observed in any of the corresponding indexes of Ani 0.1 mg/kg treatment group at different time-points compared to those of the saline group.ConclusionAni may have adverse effects on the cardio-respiratory systems of dogs at doses above 0.4 mg/kg, whereas Ani 0.1 mg/kg was devoid of potentially deleterious effects on cardiorespiratory function.

Electrochemical detection of sotalol on a magnetographite-epoxy electrode using magnetite nanoparticles

Sotalol hydrochloride (STHCl) is a cardiovascular agent, specifically an antiarrhythmic and beta-blocker, that can be used regularly for an extended period. However, it may have side effects, such as weakness and slow heart rate (bradycardia). Currently, techniques such as capillary zone electrophoresis and high-performance liquid chromatography have been widely used for the determination of sotalol hydrochloride, which increases the cost of the analysis. Hence, the aim of this study is to develop an electrochemical sensor, employing magnetographite-epoxy composite (m-GEC) electrode modified with magnetite nanoparticles (MNPs) functionalised with carboxyl for the detection of sotalol as a faster, cheaper, precise and sensitive alternative method. The MNPs have an average size of 7.5 nm and were characterised by transmission electron microscopy. The electrochemical behaviour of STHCl on the m-GEC electrode modified with MNPs, was investigated by cyclic voltammetry and differential pulse voltammetry (DPV). The supporting electrolyte was $$0.1\, \hbox {mol l}^{\mathrm {-1}}$$ of phosphate buffer solution ( $$\hbox {pH}= 7.0$$ ). Two oxidation peaks were observed: at a potential of 720 mV and at 920 mV vs. Ag/AgCl (KCl sat). Differential pulse voltammetry revealed linear calibration curves from 0.5 to $$500\times 10^{-6}\,\hbox {mol l}^{-1}$$ , with a limit of detection of $$0.015\times 10^{-6}\hbox {mol}\cdot \hbox {l}^{{-1}}$$ . Finally, the modified electrode showed good sensitivity, selectivity and stability for the determination of sotalol in real samples.

Assessment of the ecotoxicity of the pharmaceuticals bisoprolol, sotalol, and ranitidine using standard and behavioral endpoints.

The pharmaceuticals bisoprolol (BIS), sotalol (SOT), and ranitidine (RAN) are among the most consumed pharmaceuticals worldwide and are frequently detected in different aquatic ecosystems. However, very few ecotoxicity data are available in the literature for them. To help fill these data gaps, toxicity tests with the algae Raphidocelis subcapitata, the macrophyte Lemna minor, the cnidarian Hydra attenuata, the crustacean Daphnia similis, and the fish Danio rerio were performed for assessing the ecotoxicity of these pharmaceuticals. Standard, as well as non-standard endpoint, was evaluated, including the locomotor behavior of D. rerio larvae. Results obtained for SOT and RAN showed that acute adverse effects are not expected to occur on aquatic organisms at the concentrations at which these pharmaceuticals are usually found in fresh surface waters. On the other hand, BIS was classified as hazardous to the environment in the acute III category. Locomotor behavior of D. rerio larvae was not affected by BIS and RAN. A disturbance on the total swimming distance at the dark cycle was observed only for larvae exposed to the highest test concentration of 500mgL-1 of SOT. D. similis reproduction was affected by BIS with an EC10 of 3.6 (0.1-34.0) mgL-1. A risk quotient (RQ) of 0.04 was calculated for BIS in fresh surface water, considering a worst-case scenario. To the best of our knowledge, this study presents the first chronic toxicity data with BIS on non-target organisms.

Association Between Obesity-Mediated Atrial Fibrillation and Therapy With Sodium Channel Blocker Antiarrhythmic Drugs

The association between obesity, an established risk factor for atrial fibrillation (AF), and response to antiarrhythmic drugs (AADs) remains unclear. To test the hypothesis that obesity differentially mediates response to AADs in patients with symptomatic AF and in mice with diet-induced obesity (DIO) and pacing induced AF. An observational cohort study was conducted including 311 patients enrolled in a clinical-genetic registry. Mice fed a high-fat diet for 10 weeks were also evaluated. The study was conducted from January 1, 2018, to June 2, 2019. Symptomatic response was defined as continuation of the same AAD for at least 3 months. Nonresponse was defined as discontinuation of the AAD within 3 months of initiation because of poor symptomatic control of AF necessitating alternative rhythm control therapy. Outcome measures in DIO mice were pacing-induced AF and suppression of AF after 2 weeks of treatment with flecainide acetate or sotalol hydrochloride. A total of 311 patients (mean [SD] age, 65 [12] years; 120 women [38.6%]) met the entry criteria and were treated with a class I or III AAD for symptomatic AF. Nonresponse to class I AADs in patients with obesity was less than in those without obesity (30% [obese] vs 6% [nonobese]; difference, 0.24; 95% CI, 0.11-0.37; P = .001). Both groups had similar symptomatic response to a potassium channel blocker AAD. On multivariate analysis, obesity, AAD class (class I vs III AAD [obese] odds ratio [OR], 4.54; 95% Wald CI, 1.84-11.20; P = .001), female vs male sex (OR, 2.31; 95% Wald CI, 1.07-4.99; P = .03), and hyperthyroidism (OR, 4.95; 95% Wald CI, 1.23-20.00; P = .02) were significant indicators of the probability of failure to respond to AADs. Pacing induced AF in 100% of DIO mice vs 30% (P < .001) in controls. Furthermore, DIO mice showed a greater reduction in AF burden when treated with sotalol compared with flecainide (85% vs 25%; P < .01). Results suggest that obesity differentially mediates response to AADs in patients and in mice with AF, possibly reducing the therapeutic effectiveness of sodium channel blockers. These findings may have implications for the management of AF in patients with obesity.

Chronic fatigue syndrome: identification of transcription factor (TFs) associated with gene expression for drug signature prediction

Numerous unbearable chronic illnesses are characterised by the presence of fatigue, the extreme exhaustion that does not improve with rest. Chronic fatigue syndromes (CFS) is one of the most commonly reported medical complaint that demand patients to seek medical care. This fatigue becomes complex to describe being a lifelong condition and even plenty of rest fails to take it away. According to the Centre for Disease Control (CDC) and Prevention, symptoms, in addition to be diagnosed with CFS are headache, aching muscles, random sore throat, short-term memory, and unrefreshing sleep. To get the insight into CFS, GEO data are used for the identification of the differentially expressed genes involved in CFS using the GEO2R interactive web tool. The GeneSingDB curated gene signature and the MsingDB molecular signature database is used for the prediction of the regulatory transcript factors (TFs) for the differentially expressed genes using aniRegulon plug-in for Cytoscape. The L1000CDS2 web tool is used for prediction of potential small-molecule signature that matches user input signature gene expressions. Nearly 198 differentially expressed genes are found in this study (log FC > 0.1). From these, 137 genes are identified as downregulated with 15 significant TFs and 61 genes are upregulated in CFS with 23 significant associated TFs. This study also found that small-molecules BRD-A94756469, S1205, Sotalol hydrochloride, methylandrostenediol and BRD-A94756469 can potentially reverse gene expression in CFS disease.

Metal organic framework HKUST-1 modified with carboxymethyl-β-cyclodextrin for use in improved open tubular capillary electrochromatographic enantioseparation of five basic drugs.

This work shows that the metal organic framework (MOF) HKUST-1 of type Cu3(BTC)2 (also referred to as MOF-199; a face-centered-cubic MOF containing nanochannels) is a most viable coating for use in enantioseparation in capillary electrochromatography (CEC). A HKUST-1 modified capillary was prepared and characterized by scanning electron microscopy, transmission electron microscopy, Fourier transform infrared spectra, elemental analysis and thermogravimetric analysis. CEC-based enantioseparation of the basic drugs propranolol (PRO), esmolol (ESM), metoprolol (MET), amlodipine (AML) and sotalol (SOT) was performed by using carboxymethyl-β-cyclodextrin as the chiral selector. Compared with a fused-silica capillary, the resolutions are improved (ESM: 1.79; MET: 1.80; PRO: 4.35; SOT: 1.91; AML: 2.65). The concentration of chiral selector, buffer pH value, applied voltage and buffer concentration were optimized, and the reproducibilities of the migration times and Rs values were evaluated. Graphical abstract Schematic presentation of the preparation of a HKUST-1@capillary for enantioseparation ofracemic drugs. Cu(NO3)2 and 1,3,5-benzenetricarboxylic acid (BTC) were utilized to prepare the HKUST-1@capillary. Then the capillary was applied to construct capillary electrochromatography system with carboxymethyl-β-cyclodextrin (CM-β-CD) for separation of basic racemic drugs.

Screen printed carbon electrode sensor with thiol graphene quantum dots and gold nanoparticles for voltammetric determination of solatol

This work, a highly selective and sensitive sensor is described for voltammetric determination of the sotalol (SOT). The dual actions of sotalol lead to reductions in the automaticity of myocardial cells and in conduction through the atrioventricular node. Drug analysis has an extensive impact on public health. The molecularly imprinted sensor was constructed by modifying a screen printed carbon electrode (SPCE) with thiol graphene quantum dots (GQD-SH) and gold nanoparticles (AuNPs). Under optimal conditions the nanotools has a dynamic range that covers the 0.1–250 μM SOT concentration range, and the detection limit is 0.035 μM. This is lower than any of the previously reported methods. The MIP-sensor also exhibited excellent selectivity, good stability and adequate reproducibility for the detection of the SOT over its structural analogs. The prepared sensor was successfully applied to the measurement of SOT in various real samples including tablet and human blood serum.

Development of a validated spectrofluorimetric method for assay of sotalol hydrochloride in tablets and human plasma: application for stability-indicating studies

AbstractThe native fluorescence of sotalol hydrochloride (SOT) was used as a basis for establishing a new method of analysis for SOT in tablets and spiked human plasma. The fluorescence of SOT in water was measured at 310 nm when excited at 235 nm. The detection limit (LOD) was 0.37 ng/mL and the quantification limit (LOQ) was 1.08 ng/mL. The proposed method offers high sensitivity which permits determination of SOT, even if present in a very small amount, in human plasma. The obtained results were successfully compared to that of a reference pharmacopeial method and statistical analysis proved a good agreement between the results of both methods. Further investigation of the SOT stability upon exposure to various stress conditions, such as acidic, alkaline, oxidative and photolytic degradation conditions was also performed. The kinetics of acidic, alkaline and oxidative degradation of the drug showed a pseudo first order degradation reaction. A proposal of the degradation pathway was suggested and confirmed by developing a thin layer chromatographic method used for separation of SOT and its acidic and alkaline degradation products.