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Molecules (Basel, Switzerland) Nov 2018Mechanochemical ball milling catalytic transfer hydrogenation (CTH) of aromatic nitro compounds using readily available and cheap ammonium formate as the hydrogen source...
Mechanochemical ball milling catalytic transfer hydrogenation (CTH) of aromatic nitro compounds using readily available and cheap ammonium formate as the hydrogen source is demonstrated as a simple, facile and clean approach for the synthesis of substituted anilines and selected pharmaceutically relevant compounds. The scope of mechanochemical CTH is broad, as the reduction conditions tolerate various functionalities, for example nitro, amino, hydroxy, carbonyl, amide, urea, amino acid and heterocyclic. The presented methodology was also successfully integrated with other types of chemical reactions previously carried out mechanochemically, such as amide bond formation by coupling amines with acyl chlorides or anhydrides and click-type coupling reactions between amines and iso(thio)cyanates. In this way, we showed that active pharmaceutical ingredients Procainamide and Paracetamol could be synthesized from the respective nitro-precursors on milligram and gram scale in excellent isolated yields.
Topics: Aniline Compounds; Catalysis; Hydrocarbons, Aromatic; Hydrogenation; Nitro Compounds; Spectroscopy, Fourier Transform Infrared
PubMed: 30513686
DOI: 10.3390/molecules23123163 -
Cellular and Molecular Life Sciences :... Dec 2020The natriuretic peptides (NPs) family, including a class of hormones and their receptors, is largely known for its beneficial effects within the cardiovascular system to... (Review)
Review
The natriuretic peptides (NPs) family, including a class of hormones and their receptors, is largely known for its beneficial effects within the cardiovascular system to preserve regular functions and health. The concentration level of each component of the family is of crucial importance to guarantee a proper control of both systemic and local cardiovascular functions. A fine equilibrium between gene expression, protein secretion and clearance is needed to achieve the final optimal level of NPs. To this aim, the regulation of gene expression and translation plays a key role. In this regard, we know the existence of fine regulatory mechanisms, the so-called epigenetic mechanisms, which target many genes at either the promoter or the 3'UTR region to inhibit or activate their expression. The gene encoding ANP (NPPA) is regulated by histone modifications, DNA methylation, distinct microRNAs and a natural antisense transcript (NPPA-AS1) with consequent implications for both health and disease conditions. Notably, ANP modulates microRNAs on its own. Histone modifications of BNP gene (NPPB) are associated with several cardiomyopathies. The proBNP processing is regulated by miR30-GALNT1/2 axis. Among other components of the NPs family, CORIN, NPRA, NPRC and NEP may undergo epigenetic regulation. A better understanding of the epigenetic control of the NPs family will allow to gain more insights on the pathological basis of common cardiovascular diseases and to identify novel therapeutic targets. The present review article aims to discuss the major achievements obtained so far with studies on the epigenetic modulation of the NPs family.
Topics: Animals; Atrial Natriuretic Factor; Disease; Epigenesis, Genetic; Gene Expression Regulation; Humans; MicroRNAs; Natriuretic Peptides; Procainamide; Protein Processing, Post-Translational; Receptors, Atrial Natriuretic Factor
PubMed: 32556416
DOI: 10.1007/s00018-020-03573-0 -
Journal of Chromatography. B,... Jan 2023Therapeutic drug monitoring (TDM) of cardiovascular drugs is essential to improve treatment efficacy and minimize toxicity because of the usage of multiple drugs with a...
Development and validation of an analytical method using liquid chromatography-tandem mass spectrometry for the therapeutic drug monitoring of seven cardiovascular drugs in clinical usage.
Therapeutic drug monitoring (TDM) of cardiovascular drugs is essential to improve treatment efficacy and minimize toxicity because of the usage of multiple drugs with a very limited therapeutic range and the high pharmacokinetic variation in patients. We developed and validated a reliable and economical liquid chromatography/tandem mass spectrometry (LC-MS/MS) method for the determination of seven cardiovascular drugs-procainamide, lidocaine, quinidine, deslanoside, digoxin, atorvastatin, and digitoxin-for clinical usage. Serum samples were prepared by simple protein precipitation with an organic solvent consisting of acetonitrile and methanol (2:1 v/v) and analyzed under optimized LC-MS/MS conditions. The chromatographic separations were accomplished within 15 min on a reversed-phase C18 column with a gradient elution of aqueous solvent and acetonitrile while maintaining 0.1 (v/v) % formic acid and 2 mM ammonium formate. The optimized MS/MS conditions in ESI-positive mode offered sufficient sensitivity for the seven cardiovascular drugs (LOQs between 0.5 and 1 ng/mL). This method was fully validated including linearity, selectivity, accuracy, precision, carry-over, and matrix effects. Additionally, stability under several conditions was tested to determine how to handle the standard solutions and serum samples. The seven cardiovascular drugs, simultaneously, were precisely and accurately analyzed in intra- and inter-day assays (RSD < 6 % and recovery between 96.3 and 102.8 %) using only two isotope-labeled internal standards (lidocaine-(diethyl-d10) and digoxin-21, 21, 22-d3). The presented method also showed good accuracy in analyzing the seven drugs in hyperlipidemia, hyperalbuminemia, and hyperglycemia serum, allowing it to be recommended as a common and routine analysis method for cardiovascular drugs in clinical practice.
Topics: Humans; Chromatography, Liquid; Cardiovascular Agents; Tandem Mass Spectrometry; Drug Monitoring; Solvents; Digoxin; Lidocaine; Chromatography, High Pressure Liquid; Reproducibility of Results
PubMed: 36469961
DOI: 10.1016/j.jchromb.2022.123552 -
Green Alternatives in Pharmaceutical and Bioanalytical Analysis of TDM Required Drugs: Procainamide.Combinatorial Chemistry & High... 2023In drug analysis, using non-hazardous solvents instead of the ones harmful to humans and the environment is a green strategy to protect analysts and environmental health.
INTRODUCTION
In drug analysis, using non-hazardous solvents instead of the ones harmful to humans and the environment is a green strategy to protect analysts and environmental health.
OBJECTIVE
Procainamide (PCA) is an antiarrhythmic drug requiring therapeutic drug monitoring (TDM) because of its narrow therapeutic window and serious side effects.
AIM
The aim of this study is to develop validated green HPLC methods to be used in drug quality control and TDM analysis for PCA, thus indicating the further applicability in the analysis of TDM-required drugs, such as immunosuppressants, anti-cancer drugs, and psychiatric drugs.
METHODS
Human-friendly ethanol was selected as an organic solvent in the mobile phase. PCA was eluted from NUCLEODUR 100-5 C8 ec (5 μm, 150 x 4.6 mm) column by a mobile phase containing ethanol and 50 mM NaHPO buffer (5:95, v/v). The mobile phase flow rate was 1.0 ml min, the column temperature was 35 °C, and the wavelength at the PDA detector was 278 nm.
RESULTS
Retention time for PCA was 5.0 min and 7.7 min for paracetamol as an internal standard (IS). In the green HPLC method for pharmaceutical analysis, the highest relative standard deviation (RSD) and mean recovery values were 1.32% and 98.89%, respectively. In the analysis of plasma, the sample preparation step was only smooth protein precipitation by ethanol. Thus, the bioanalytical method was fully green having a limit of detection (LOD) of 0.3 μg ml and a limit of quantification (LOQ) of 0.8 μg ml. The therapeutic plasma concentration for PCA was reported in the range of 4-12 μg ml.
CONCLUSION
As a result, the green HPLC methods developed and validated in this study were selective, accurate, precise, reproducible, and trustable and have the quality for the application in pharmaceutical and TDM analysis of PCA, thus encouraging green HPLC analysis of other TDM required drugs.
Topics: Humans; Procainamide; Limit of Detection; Pharmaceutical Preparations; Ethanol; Chromatography, High Pressure Liquid; Reproducibility of Results
PubMed: 36999693
DOI: 10.2174/1386207326666230331083215 -
Drug Safety - Case Reports Sep 2019Systemic lupus erythematosus (SLE) can be induced by various medications, such as hydralazine, procainamide, isoniazid, methyldopa, chlorpromazine, quinidine, and...
Systemic lupus erythematosus (SLE) can be induced by various medications, such as hydralazine, procainamide, isoniazid, methyldopa, chlorpromazine, quinidine, and minocycline. A patient was admitted complaining of fever with chills and rigor. After being diagnosed with tuberculous meningitis, the patient was given antituberculosis treatment. As the patient did not improve, detailed investigations were conducted, and elevated antinuclear antibody levels were found. The consulting physician diagnosed that the patient was suffering from SLE. As isoniazid is associated with an increased risk of developing SLE, it was suspected as the culprit drug. After withdrawing isoniazid from the antituberculosis treatment regimen, the patient improved and was discharged. Based on the WHO-UMC and Naranjo's causality assessment criteria, an association between the reaction and isoniazid was deemed probable. The reaction was moderately severe (level 4b) according to the modified Hartwig and Siegel scale.
PubMed: 31541371
DOI: 10.1007/s40800-019-0102-y -
JACC. Clinical Electrophysiology Apr 2019
Topics: Ajmaline; Anti-Arrhythmia Agents; Brugada Syndrome; Humans; NAV1.5 Voltage-Gated Sodium Channel; Procainamide
PubMed: 31000107
DOI: 10.1016/j.jacep.2019.03.003 -
International Journal of Molecular... Aug 2022Glycosylation is vital for well-functioning glycoproteins and is reportedly altered in chronic inflammatory disorders, including multiple sclerosis (MS). High-throughput...
Glycosylation is vital for well-functioning glycoproteins and is reportedly altered in chronic inflammatory disorders, including multiple sclerosis (MS). High-throughput quantitative measurement of protein glycosylation is challenging, as glycans lack fluorophore groups and require fluorescent labeling. The attachment of fluorescent tags to each glycan moiety necessitates sample clean-up for reliable quantitation. The use of magnetic particles in glycan sample preparation is reportedly an easy-to-use solution to accomplish large-scale biomarker discovery studies. In this study, NH-funtionalized magnetic nanoparticles were synthetized, characterized and applied for the glycosylation analysis of serum samples from patients diagnosed with multiple sclerosis and corresponding healthy controls. Serum samples were PNGase F digested and labeled by procainamide via reductive amination, followed by magnetic nanoparticle-based purification. The prepared samples were analyzed by hydrophilic interaction liquid chromatography, allowing for the relative quantitation of the individual glycan species. Significant glycosylation alterations were detected between MS patients and healthy controls, especially when analyzing the different gender groups.
Topics: Glycomics; Glycosylation; Humans; Magnetite Nanoparticles; Multiple Sclerosis; Polysaccharides
PubMed: 36012360
DOI: 10.3390/ijms23169095 -
Advanced Emergency Nursing JournalAtrial fibrillation/flutter (AF) remains the most common rhythm disturbance in adult patients presenting to emergency departments (EDs). Although pharmacologic...
Atrial fibrillation/flutter (AF) remains the most common rhythm disturbance in adult patients presenting to emergency departments (EDs). Although pharmacologic cardioversion has been established as safe and effective in recent-onset AF, its use in U.S. EDs is uncommon. The purpose of this study was to assess the safety and efficacy of intravenous (IV) procainamide for pharmacologic cardioversion in patients presenting to the ED with AF of <48-hr duration. Patients presenting to the ED with recent-onset AF (<48 hr) undergoing a cardioversion strategy with IV procainamide from 2017 to 2019 were reviewed. Clinical outcomes assessed included rates of cardioversion, hospital admission, stroke, and return ED visits for arrhythmia or serious adverse events. A total of 64 patients received procainamide therapy-60.9% achieved cardioversion and 35.9% were admitted to the hospital. The mean dose was 1062.4 mg (12.1 mg/kg). No patients returned to the ED secondary to stroke and 9.4% experienced complications attributed to procainamide, the most common being hypotension. Within 30 days of therapy, 20.3% of patients returned to the ED secondary to arrhythmia recurrence. Patients experiencing cardioversion with procainamide were less likely to be admitted to the hospital (25.6% vs. 52.0%; p = 0.04) or receive a rate control agent (17.9% vs. 64.0%; p = 0.001). There was no significant difference in the rate of 30-day return between those who experienced pharmacologic cardioversion and those who did not (p = 0.220). The implementation of a procainamide-based acute cardioversion strategy for patients presenting to the ED with recent-onset AF resulted in a 60% cardioversion rate, which was associated with a significantly higher rate of discharge from the ED. Transient hypotension was the most common adverse event. Further investigation into ED-based protocols for management of recent-onset AF is necessary to better understand their safety and efficacy.
Topics: Anti-Arrhythmia Agents; Atrial Fibrillation; Emergency Service, Hospital; Female; Humans; Infusions, Intravenous; Male; Middle Aged; Procainamide; Retrospective Studies
PubMed: 34397493
DOI: 10.1097/TME.0000000000000358 -
PloS One 2016Excessive inflammatory and oxidative stress lead to circulatory failure, multiple organ dysfunction, and high mortality in patients with sepsis. Microbial...
Excessive inflammatory and oxidative stress lead to circulatory failure, multiple organ dysfunction, and high mortality in patients with sepsis. Microbial infection-induced DNA hypermethylation is associated with the augmentation of inflammation and oxidative stress. In our previous study, the antiarrhythmic drug procainamide inhibits the expression of DNA methyltransferase 1 (DNMT1) and diminishes IL-6 levels in rats with rhabdomyolysis. Thus, we further evaluated the effects of procainamide on the development of circulatory failure and multiple organ dysfunction in rats with endotoxic shock. Male Wistar rats were intravenously infused with saline or lipopolysaccharide (LPS) followed by procainamide administration. The changes of hemodynamics, blood glucose, biochemical variables, and plasma nitric oxide (NO) levels were analyzed during the experimental period. At the end of experiments, animal organs were also obtained for examining superoxide production, neutrophil infiltration, and DNA methylation status. Our results showed that LPS induced circulatory failure, multiple organ dysfunction, and high mortality rate in endotoxemic rats. Overt neutrophil infiltration and superoxide production, accompanied by the elevations of DNMT1 and 5-methylcytosine levels in the lung of endotoxemic rats were also observed. Treatment of endotoxemic animals with procainamide not only inhibited the increased levels of DNMT1 and 5-methylcytosine but also ameliorated neutrophil infiltration and superoxide production in the lung. In addition, the anti-inflammatory gene, IL27RA, was down-regulated in the LPS group and up-regulated in the LPS + Procainamide group. Procainamide also diminished IL27RA methylation in the lung of endotoxemic rat. Moreover, both DNMT inhibitors procainamide and hydralazine improved hypotension, hypoglycemia, and multiple organ dysfunction of LPS-treated rats. Thus, we suggest that the beneficial effects of procainamide could be attributed to the suppression of DNA methylation, neutrophil infiltration, superoxide production, and NO formation. It seems that this old drug may have new potential uses in infectious diseases, in particular, associated with endotoxemia.
PubMed: 27661616
DOI: 10.1371/journal.pone.0163690 -
Hospital Pharmacy Nov 2017The objective of this study was to evaluate the chemical stability of procainamide hydrochloride, 100 mg/mL, when repackaged in clear glass vials or diluted to 3 mg/mL...
OBJECTIVES
The objective of this study was to evaluate the chemical stability of procainamide hydrochloride, 100 mg/mL, when repackaged in clear glass vials or diluted to 3 mg/mL with normal saline and packaged in polyvinyl chloride (PVC) bags when stored at either 23°C and exposed to light (ETL) or 5°C and protected from light (PFL).
METHODS
Solutions were assayed using a stability-indicating high-performance liquid chromatography method. Samples (5 mL) were collected from triplicate containers on days 0, 7, 14, 21, 28, 56, 91, and 193. Color/clarity and pH changes were also monitored at each time interval.
RESULTS
During the study, all samples remained clear and there was only a slight pH change. The color of the solutions stored at 23°C intensified but did not correlate with a significant decrease in concentration, while solutions stored at 5°C remained unchanged. Solutions repackaged in glass vials were stable for 193 days when stored at 23ºC and ETL or 5ºC and PFL. When further diluted to 3 mg/mL with normal saline and packaged in PVC bags, procainamide was also stable for 193 days at either 23ºC and ETL or 5°C and PFL.
CONCLUSIONS
The stability of procainamide, 100 mg/mL, repackaged in clear glass vials was 193 days when stored at either 23ºC and ETL or 5ºC or PFL. If diluted further to 3 mg/mL with normal saline and packaged in PVC bags, the drug was also stable for 193 days at either 23ºC and ETL or 5°C and PFL.
PubMed: 29276243
DOI: 10.1177/0018578717724896