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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 -
RSC Advances Mar 2023First-principle calculations were systematically carried out to explore the structural and electronic properties of the non-covalent interaction of procainamide (PA)...
Non-covalent interaction, adsorption characteristics and solvent effect of procainamide anti-arrhythmias drug on silver and gold loaded silica surfaces: SERS spectroscopy, density functional theory and molecular docking investigations.
First-principle calculations were systematically carried out to explore the structural and electronic properties of the non-covalent interaction of procainamide (PA) anti-arrhythmias drug molecules on silver-loaded and gold-loaded silica nanostructures. Computed adsorption energies presented a higher affinity of PA towards the Ag-SiO as compared with Au-SiO surfaces. The non-covalent interaction analysis revealed a weak van der Waals type of forces and hydrogen bonding, associated with a noticeable repulsive steric interaction. It was conceived that silver and gold decorated silica can be used for drug administration in biological systems due to the fact that their frontier molecular orbital energy levels were considerably altered upon absorption, decreasing the pertinent energy gaps. Moreover, the electronic spectra of PA⋯Ag-SiO and PA⋯Au-SiO structures investigated in different solvents display a notable blue shift, suggesting that noble metal-loaded silica can be effective in the context of drug delivery systems. Therefore, silver- and gold-decorated silica of three possible drug adsorption scenarios was fully analyzed to realize the associated bioactivity and drug likeness. Theoretical findings suggest that Ag- and Au-SiO nanocomposites can be considered potential drug delivery platforms for procainamide in medication protocols.
PubMed: 36968042
DOI: 10.1039/d3ra00514c -
Molecules (Basel, Switzerland) Feb 2023The 4-amino-N-[2 (diethylamino) ethyl] benzamide (procainamide)-tetraphenylborate complex was synthesized by reacting sodium tetraphenyl borate with 4-amino-N-[2...
The 4-amino-N-[2 (diethylamino) ethyl] benzamide (procainamide)-tetraphenylborate complex was synthesized by reacting sodium tetraphenyl borate with 4-amino-N-[2 (diethylamino) ethyl] benzamide, chloride salt, and procainamide in deionized water at room temperature through an ion-associate reaction (green chemistry) at room temperature, and characterized by several physicochemical methods. The formation of ion-associate complex between bio-active molecules and/or organic molecules is crucial to comprehending the relationships between bioactive molecules and receptor interactions. The solid complex was characterized by infrared spectra, NMR, elemental analysis, and mass spectrometry, indicating the formation of ion-associate or ion-pair complex. The complex under study was examined for antibacterial activity. The ground state electronic characteristics of the S1 and S2 complex configurations were computed using the density functional theory (DFT) approach, using B3LYP level 6-311 G(d,p) basis sets. R = 0.9765 and 0.9556, respectively, indicate a strong correlation between the observed and theoretical H-NMR, and the relative error of vibrational frequencies for both configurations was acceptable, as well. HOMO and LUMO frontier molecular orbitals and molecular electrostatics using the optimized were used to obtain a potential map of the chemical. The → π* UV absorption peak of the UV cutoff edge was detected for both configurations of the complex. Spectroscopic methods were structures used to characterize the structure (FT-IR and 1HNMR). In the ground state, DFT/B3LYP/6-311G(d,p) basis sets were used to determine the electrical and geometric properties of the S1 and S2 configurations of the title complex. Comparing the observed and calculated values for the S1 and S2 forms, the HOMO-LUMO energy gap of compounds was 3182 and 3231 eV, respectively. The small energy gap between HOMO and LUMO indicated that the compound was stable. In addition, the MEP reveals that positive potential sites were around the PR molecule, whereas negative potential sites were surrounding the TPB site of atoms. The UV absorption of both arrangements is comparable to the experimental UV spectrum.
PubMed: 36903501
DOI: 10.3390/molecules28052256 -
Brazilian Journal of Medical and... 2023Procainamide (PA) and its in vivo metabolite, N-acetylprocainamide (NAPA), display some pharmacological differences. Although it is agreed that PA is a class IA...
Molecular basis of the different effects of procainamide and N-acetylprocainamide on the maximum upstroke velocity and half-decay time of the cardiac action potential in guinea pig papillary muscle.
Procainamide (PA) and its in vivo metabolite, N-acetylprocainamide (NAPA), display some pharmacological differences. Although it is agreed that PA is a class IA antiarrhythmic, it has been reported that NAPA is a pure class III antiarrhythmic that affects only the repolarizing phase of the cardiac action potential. This last concept, observed exclusively in dogs, gained wide acceptance, appearing in classic pharmacology textbooks. However, evidence in species such as mice and rats indicates that NAPA can affect cardiac Na+ channels, which is unexpected for a pure class III antiarrhythmic drug. To further clarify this issue, the effects of PA (used as a reference drug) and NAPA on the maximum upstroke velocity (Vmax) and half-decay time (HDT) of the cardiac action potential were examined in the isolated right papillaris magnus of the guinea pig heart. Both PA and NAPA affected Vmax at lower concentrations than required to affect HDT, and NAPA had weaker effects on both variables. Thus, NAPA displayed typical class IA antiarrhythmic behavior. Therefore, the concept that NAPA is a pure class III antiarrhythmic drug is more species-dependent than previously envisioned. In addition, we demonstrated that the differential pharmacology of PA and NAPA is explainable, in molecular terms, by steric hindrance of the effects of NAPA and the greater number of potent aromatic-aromatic and cation π interactions with Na+ or K+ cardiac channels for PA.
Topics: Guinea Pigs; Animals; Dogs; Mice; Rats; Procainamide; Acecainide; Papillary Muscles; Anti-Arrhythmia Agents; Action Potentials
PubMed: 36722655
DOI: 10.1590/1414-431X2023e12073 -
Molecules (Basel, Switzerland) Jan 2023As a result of the paucity of treatment, Leishmaniasis continues to provoke about 60,000 deaths every year worldwide. New molecules are needed, and drug discovery...
BACKGROUND
As a result of the paucity of treatment, Leishmaniasis continues to provoke about 60,000 deaths every year worldwide. New molecules are needed, and drug discovery research is oriented toward targeting proteins crucial for parasite survival. Among them, trypanothione reductase (TR) is of remarkable interest owing to its vital role in species protozoan parasite life. Our previously identified compound is a novel chemotype endowed with a unique mode of TR inhibition thanks to its binding to a formerly unknown but druggable site at the entrance of the NADPH binding cavity, absent in human glutathione reductase (hGR).
METHODS
We designed and synthesized new 3-amino-1-arylpropan-1-one derivatives structurally related to compound and evaluated their potential inhibition activity on TR from (LiTR). Cluster docking was performed to assess the binding poses of the compounds.
RESULTS
The newly synthesized compounds were screened at a concentration of 100 μM in in vitro assays and all of them proved to be active with residual activity percentages lower than 75%.
CONCLUSIONS
Compounds and were the most potent inhibitors found, suggesting that an additional aromatic ring might be promising for enzymatic inhibition. Further structure-activity relationships are needed to optimize our compounds activity.
Topics: Humans; Leishmania infantum; NADP; Models, Molecular; NADH, NADPH Oxidoreductases; Binding Sites; Antiprotozoal Agents
PubMed: 36615531
DOI: 10.3390/molecules28010338 -
Chemistry & Biodiversity Jan 2023Taxus wallichiana Zucc. is a high valued medicinal plant and has been mainly studied for its anti-cancer properties. However, research on its other important biological...
Taxus wallichiana Zucc. is a high valued medicinal plant and has been mainly studied for its anti-cancer properties. However, research on its other important biological activities, such as its antimicrobial potential, still needs attention. The focus of the present study is to investigate the antimicrobial activity of secondary metabolites of T. wallichiana needles against 3 different groups of microorganisms, i. e., bacteria, actinobacteria, and fungi. Bioactive compounds from T. wallichiana needles were separated through column chromatography, and, TLC-bioautography. Mobile phases were optimized using Snyder's selectivity triangle. Antimicrobial spots were fractionated and compounds were identified by gas chromatography-mass spectroscopy (GC/MS) and liquid chromatography-mass spectrometry (LC/MS). Functional groups were characterized using Fourier transform infrared spectrometry (FTIR) and nuclear magnetic resonance (NMR) was used to identify the molecular structures. GC/MS and LC/MS data analysis confirm the presence of fatty acids (arachidic acid, behenic acid, palmitic acid, and stearic acid), vitamins (nicotinamide), and alkaloids (cinchonine, timolol), aminobenzamides (procainamide), carbocyclic sugar (myoinositol), and alkane hydrocarbon (hexadecane), having antimicrobial activity in the needles of T. wallichiana. To the best of our knowledge, this is the first report on the isolation and characterization of antimicrobial compounds from the needles of Taxus wallichiana (Himalayan yew). The data obtained from the present study will be supportive to the new drug discoveries in modern medicine with various combinations of medicinal plant's active constituents that can be used for curing many diseases.
Topics: Taxus; Alkaloids; Plants, Medicinal; Chromatography, Liquid; Anti-Infective Agents
PubMed: 36574478
DOI: 10.1002/cbdv.202200572 -
Medical Sciences (Basel, Switzerland) Dec 2022Brugada syndrome (BrS) is diagnosed in patients with ST-segment elevation with coved-type morphology in the right precordial leads, occurring spontaneously or after...
BACKGROUND
Brugada syndrome (BrS) is diagnosed in patients with ST-segment elevation with coved-type morphology in the right precordial leads, occurring spontaneously or after provocative drugs. Due to electrocardiographic (ECG) inconsistency, provocative drugs, such as sodium-channel blockers, are useful for unmasking BrS. Ajmaline is superior to flecainide and procainamide to provoke BrS. Prolonged T-peak to T-end (TpTe) is associated with an increased risk of ventricular arrhythmia and sudden cardiac death in Brugada syndrome patients.
OBJECTIVE
This study aimed to investigate the predictive value of T-peak to T-end interval and corrected T-peak to T-end interval for predicting the positive response of the ajmaline challenge test in suspected Brugada syndrome patients.
METHODS
Patients who underwent the ajmaline test in our center were enrolled. Clinical characteristics and electrocardiographic parameters were analyzed, including TpTe, corrected TpTe, QT, corrected QT(QTc) interval, and S-wave duration, compared with the result of the ajmaline challenge test.
RESULTS
The study found that TpTe and corrected TpTe interval in suspected BrS patients were not significantly associated with a positive response to the ajmaline challenge test.
CONCLUSIONS
The T-peak to T-end interval and corrected T-peak to T-end interval could not predict the positive response of the ajmaline challenge test in suspected Brugada syndrome patients.
Topics: Humans; Ajmaline; Brugada Syndrome; Flecainide; Sodium Channel Blockers; Procainamide
PubMed: 36548004
DOI: 10.3390/medsci10040069 -
Journal of Chromatography. B,... Jan 2023N-glycans in glycoproteins can affect physicochemical properties of proteins; however, some reported N-glycan structures are inconsistent depending on the type of...
Peptide-N-glycosidase F or A treatment and procainamide-labeling for identification and quantification of N-glycans in two types of mammalian glycoproteins using UPLC and LC-MS/MS.
BACKGROUND
N-glycans in glycoproteins can affect physicochemical properties of proteins; however, some reported N-glycan structures are inconsistent depending on the type of glycoprotein or the preparation methods.
OBJECTIVE
To obtain consistent results for qualitative and quantitative analyses of N-glycans, N-glycans obtained by different preparation methods were compared for two types of mammalian glycoproteins.
METHODS
N-glycans are released by peptide-N-glycosidase F (PF) or A (PA) from two model mammalian glycoproteins, bovine fetuin (with three glycosylation sites) and human IgG (with a single glycosylation site), and labeled with a fluorescent tag [2-aminobenzamide (AB) or procainamide (ProA)]. The structure and quantity of each N-glycan were determined using UPLC and LC-MS/MS.
RESULTS
The 21 N-glycans in fetuin and another 21 N-glycans in IgG by either PF-ProA or PA-ProA were identified using LC-MS/MS. The N-glycans in fetuin (8-13 N-glycans were previously reported) and in IgG (19 N-glycans were previously reported), which could not be identified by using the widely used PF-AB, were all identified by using PF-ProA or PA-ProA. The quantities (%) of the N-glycans (>0.1 %) relative to the total amount of N-glycans (100 %) obtained by AB- and ProA-labeling using LC-MS/MS had a similar tendency. However, the absolute quantities (pmol) of the N-glycans estimated using UPLC and LC-MS/MS were more efficiently determined with ProA-labeling than with AB-labeling. Thus, PF-ProA or PA-ProA allows for more effective identification and quantification of N-glycans than PF-AB in glycoprotein, particularly bovine fetuin. This study is the first comparative analysis for the identification and relative and absolute quantification of N-glycans in glycoproteins with PF-ProA and PA-ProA using UPLC and LC-MS/MS.
Topics: Animals; Cattle; Humans; Chromatography, Liquid; Glycoproteins; Immunoglobulin G; Mannosyl-Glycoprotein Endo-beta-N-Acetylglucosaminidase; Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase; Peptides; Polysaccharides; Procainamide; Tandem Mass Spectrometry
PubMed: 36493594
DOI: 10.1016/j.jchromb.2022.123538 -
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 -
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