BackgroundVasoactive drugs are widely used during the perioperative period. Different vasoactive drugs have specific recommended solutions for dilution as stated in their instructions, but non-recommended solutions are sometimes used in clinical practice. The impact of using non-recommended solutions on drug stability remains unclear. This study investigated the stability of various commonly used vasoactive drugs diluted with five commonly used solutions—0.9% sodium chloride injection, sodium lactate Ringer’s injection, glucose sodium chloride injection, 5% glucose injection, and 10% glucose injection—under room temperature (24 °C ± 1 °C) without light protection.MethodsEach drug was diluted to clinically common concentrations using the five solutions mentioned above. Five samples of 100 µL each were prepared for each drug. The samples were stored at room temperature without light protection and observed at 0, 2, 4, 6, and 8 h for changes in appearance and pH. High-performance liquid chromatography (HPLC) was used to measure the drug content at each time point. The drug content at 0 h was set as 100%, and the content at other time points was calculated relative to this baseline.ResultsWithin 8 h, all solutions remained clear and transparent. Except for amiodarone hydrochloride, nicardipine hydrochloride, propafenone hydrochloride, and diltiazem hydrochloride, which showed significant pH changes after dilution, the pH changes of the other solutions were less than 0.1. Except for isoproterenol hydrochloride, the content of the other tested drugs showed no significant differences within 8 h.ConclusionWhen diluted with the five commonly used solutions and stored at room temperature without light protection for 8 h, the tested drugs maintained stable properties.

The generic and most probable synthetic route for the preparation of propafenone (PFN) has been evaluated, common toxic impurities have been identified, their in silico toxicity has been assessed, and novel UPLC-MS/MS method was developed for the identification and quantification of five potential toxic impurities (PGIs) in the active pharmaceutical ingredients of PFN, a Class 1C antiarrhythmic agent. Five PGIs were identified for this study, namely 1-2-3-amino impurity, 1-2-2-hydroxy impurity, 1-2-oxiran impurity, propafenone, EP-Impurity-C, and EP-Impurity-E and were validated following the International Conference of Harmonization (ICH) guidelines, this methodology is capable of quantifying five PGIs at 1.6 ppm with a sample concentration of 20 mg/mL. This validated approach presented very low LOD and LOQ limits (0.08-0.2 ppm), excellent linearity (coefficients > 0.9944), and a satisfactory recovery range (88.1%-102.8%). The method was sufficient in terms of sensitivity, linearity, precision, accuracy, selectivity, and robustness, and marketed samples analysis also proved that the method could directly apply for the PFN drug substance of real-time sample testing.

Propafenone is an antiarrhythmic medication with the properties that span both class 1 and class 2 antiarrhythmic drugs. It regulates the heart rhythm through the blockage of sodium channel, potassium channel, and beta receptors. In the literature, there are studies related to the effects of Propafenone on atrial fibrillation, as well as its potential anti-cancer and anti-epileptic effects. However, there is currently insufficient research on Propafenone's immunomodulatory effects. In this study, the immunomodulatory activity of propafenone was tested. Impact of Propafenone on TNF-α, IL-6, Il-12p40 and GM-CSF cytokines production by J774.2 macrophage cell line was evaluated in the presence and absence of LPS (lipopolysaccharide). Cytokine production level was tested in the presence of propafenone. The results showed that Propafenone alone did not significantly stimulate cytokine release, but in the presence of LPS, it showed a significant effect and demonstrated anti-inflammatory activity. Propafenone has anti-inflammatory activity. At the clinical setting this information should be taken into the consideration if anti-inflammatory drug utilization is also necessary to prevent extra usage of the drug molecules. In case of infections, the patients who are using propafenone should get immune boosting supplements to be able to cope with the infectious agent.

Premature ventricular contraction (PVC) is a common type of arrhythmia, and obstructive sleep apnea (OSA) is a common trigger for this condition. Some patients still have PVC, even if ventilation is improved by wearing a respirator. Traditional Chinese medicine (TCM) has a long history of arrhythmia treatment, and this is the first report of a patient with PVC caused by OSA treated with TCM. Twenty-four-hour Holter showed that the number of PVCs decreased from 8968 to 0 before and after TCM treatment, and discomfort symptoms disappeared completely. A 37-year-old middle-aged man, with no history of hypertension, diabetes, hyperlipidemia, or other underlying diseases, had been suffering from OSA for over 1 year and currently uses a respirator to sleep. He was diagnosed with PVC at Beijing Anzhen Hospital 1 year ago and had been taking propafenone hydrochloride tablets following the physician's advice, but palpitation had not been relieved. The patient did not consider surgery and hoped to take TCM to treat the palpitations. The patient was diagnosed with PVC. After excluding other factors that could cause PVC, it was ultimately considered that the patient's PVC was related to OSA. The patient visited Xiyuan Hospital on December 5, 2023, on the basis of existing Western medicine and TCM, using the modified Huanglian Wendan Decoction. After taking TCM for 21 days, the Holter tests were conducted again. The results showed that the number of PVCs decreased from 8968 to 0 within 24 hours. Meanwhile, his palpitations were relieved, and the dosage of propafenone hydrochloride tablets was halved. After 7 days, he did not experience any discomfort; therefore, propafenone hydrochloride tablets were discontinued and TCM was exclusively administered. He received 7 additional courses in TCM. During the final consultation on April 23, 2024, the patient reported no discomfort, and snoring improved. After treatment with TCM, the patient's palpitations disappeared completely and snoring improved, which proved that TCM can treat PVC caused by OSA. To verify this conclusion, more high-quality research is necessary to establish the efficacy and underlying mechanisms of TCM in treating PVC caused by OSA.

Purpose: To investigate the effects of amiodarone hydrochloride tablets combined with potassium magnesium aspartate on hemodynamics and cardiac function in coronary heart disease (CHD) patients with arrhythmia.Methods: In this retrospective research, a total of 110 CHD and arrhythmia patients on admission at Jiaozhou Central Hospital of Qingdao from June 2020 to June 2022 were randomly but equally divided into control group (CG) treated with propafenone hydrochloride tablets, and study group (SG) treated with a combination of amiodarone hydrochloride tablets and potassium magnesium aspartate. Clinical efficacy of the treatment types as well as the number of premature ventricular contractions (PVC), QTc interval and heart rate (HR) of the patients were monitored to determine left ventricular end-diastolic diameter (LVEDD), left ventricular end-systolic diameter (LVESD), and cardiac index (CI). Fibrinogen levels, plasma viscosity and hematocrit of the patients were also assessed.Results: The total effectiveness/efficacy of treatment in SG was 92.73 %, which was significantly higher than the corresponding CG value of 76.36 % (p < 0.05). Relative to CG, PVC and HR in SG were significantly lower, while QTc interval was significantly higher. The levels of LVESD and LVEDD were significantly lower in SG than in CG, while CI level was significantly higher. However, fibrinogen, plasma viscosity and hematocrit values were significantly lower in SG than in CG (p < 0.05).Conclusion: When administered along with potassium magnesium aspartate in the treatment of CHD and arrhythmia, amiodarone hydrochloride tablets enhances clinical efficacy and improves electrocardiograph index, hemodynamics and cardiac function. Nonetheless, there is need for expanded clinical trials before the use of this treatment strategy in clinical practice.

Voltammetric Study of the Complexation of Propafenone Hydrochloride (Rythmol SR) with Co2+, Ni2+, Zn2+, and Mn2+ Ions

Elemental impurities are substances present in drug products, excipients, or drug formulations. They may be formed by the presence of catalysts and environmental contaminants. Elemental impurities can be detected by a sophisticated method such as Inductively Coupled Plasma Mass Spectrometry (ICP–MS). ICP-MS is an advanced method to detect elemental impurities in drug substances. In this study Propafenone hydrochloride drug was used, Propafenone Hydrochloride is an antiarrhythmic medication belonging to class 1C used to prevent supraventricular and ventricular arrhythmias. The present study was aimed to develop and validate inductively coupled plasma mass spectroscopic (ICP–MS) method for detection of elemental contaminants, i.e., Class 1, Cd, Pb, As, Class 2A, Hg, Co, V, and Class 2B impurities such as Ni, T1, Se, Ag, Au, Pd, Ir, Os, Rh, Ru, and Pt. Total 17 elemental impurities were detected in Propafenone Hydrochloride and this method was employed for the regular sample analysis of 17 elemental impurities in Propafenone Hydrochloride for pharmaceutical use. The instrument conditions were set using RF power of 1550 W, auxiliary gas of 0.5 L/min, and nebulizer flow of 1.01 L/min nebulizer pump pressure was 0.10 rps, spray chamber temperature was 2°C, and mode used was He, He flow rate was 4.3 mL/min and the energy discrimination rate was 3.0 V. The technique is sensitive and may identify desirable elemental impurities within permissible regulatory limits when additional elements are present. The proposed ICP-MS approach has been found to be accurate, precise, linear, rugged, robust, and convenient for the quality control of the drug substance propafenone hydrochloride. The linearity results for each impurity were 0.9990. The methods were validated according to USP requirements and International Council for Harmonization ICH guidelines. The suggested approach is an excellent quality control tool for the concurrent quantitative assessment and detection of elemental contaminants at low levels in the drug substance propafenone hydrochloride.

During the dissolution of drug salt particles, liquid-liquid phase separation (LLPS) of a free form can occur within the unstirred water layer (UWL) of the particles (UWL-LLPS). Theoretically, UWL-LLPS occurs when the free form concentration at the salt particle surface (C0) exceeds the intrinsic LLPS concentration (S0LLPS) of the free form. In the present study, we attempted to predict UWL-LLPS based on the intrinsic physicochemical properties of drugs. Cyproheptadine hydrochloride (CPH-HCl), diclofenac sodium (DCF-Na), papaverine hydrochloride (PAP-HCl), and propafenone hydrochloride (PRF-HCl) were selected as model drug salts. The pH0 and C0 values at pHs 4.0-9.5 (citric acid, phosphoric acid, and boric acid, buffer capacity = ca. 4 mM/ΔpH) were calculated using the pKa, solubility product (Ksp), and diffusion coefficient (D) of a drug. S0LLPS was measured using the pH-shift method. UWL-LLPS was predicted to occur when C0 ≥ S0LLPS. The prediction result was then compared with UWL-LLPS observed at each pH by polarized light microscopy (PLM). The pH-LLPS concentration (SpHLLPS) profile of each drug was also measured. UWL-LLPS was approximately correctly predicted for CPH-HCl, DCF-Na, and PRF-HCl. However, UWL-LLPS was not observable when C0 was close to S0LLPS. Furthermore, UWL-LLPS was not accurately predicted in the case of PAP-HCl. The pH-SpHLLPS profile of PAP did not follow the Henderson-Hasselbalch equation, probably because of the formation of cationic aggregates. In conclusion, UWL-LLPS was approximately predictable for drug salts using their intrinsic physicochemical properties (Ksp, pKa, D, and S0LLPS), except for PAP-HCl.

In order to further clarify the accuracy of drug interactions. Clinicians participated in the treatment and rescue of a patient with hypotensive shock caused by the combination of metoprolol and propafenone hydrochloride. According to the patient's condition, they read relevant references and combined pharmaceutical knowledge, clinical thinking and evidencebased medicine principles to provide basic research on the correlation between drug interactions. Resultly, we get a clear understanding of the interactions between drugs, which can provide clinicians with accurate medication plans, provide patients with individualized pharmaceutical care, and ensure safe and rational drug use by clinicians.

ObjectivesIn children, supraventricular tachycardia is the most common form of arrhythmia, and propafenone is an effective class Ic antiarrhythmic agent used in this population. No suitable paediatric-specific, dosing-flexible preparation is...

Ratiometric detection of propafenone hydrochloride with one-pot synthesized dual emissive carbon dots

Chemoenzymatic synthesis of both enantiomers of propafenone hydrochloride through lipase-catalyzed process

Introduction: Even though some studies have implicated radiation therapy (RT) as a risk factor for atrial fibrillation (AF), the association between RT and AF remains controversial. Hypothesis: To estimate the risk of AF associated with RT and compare it with dobutamine, flecainide, propafenone, ibrutinib and adenosine - the most common drugs causing AF. Methods: The US Food and Drug Administration’s Adverse Event Reporting System (FAERS) was queried for “Atrial fibrillation (AF)” secondary to “radiation therapy”, “Dobutamine”, “dobutamine hydrochloride”, “dobutamine hydrochloride in dextrose”, “flecainide”, “flecainide acetate”, “propafenone”, “propafenone hcl”, “propafenone hydrochloride”, “propafenone hydrochloride sr”, “ibrutinib” and “adenosine” and all other drugs on May 25, 2021. Disproportionality signal analysis was performed by calculating the reporting odds ratio (ROR) with its 95% confidence interval (CI). The ROR was considered significant when the lower limit of the 95% CI was >1.0. Results: FAERS database has a total of 22,002,078 AE reported till May 25, 2021. The ROR (95% CI) for AF due to RT versus all other drugs in FAERS was 3.9 (2.9 to 5.3) signifying disproportionately increased reporting. ROR (95%CI) for AF due to dobutamine, flecainide, propafenone, ibrutinib and adenosine was 18.2 (15.6 to 21.3), 19.0 (17.0 to 21.2), 35.9 (32.5 to 39.7), 16.6 (15.9 to 17.4) and 10.0 (7.4 to 13.6) respectively. Conclusions: While there is significantly higher reporting of AF with RT, this risk is lower when compared to the most common causes of drug induced AF.

Synergistic effect of Aconiti Lateralis Radix Praeparata water-soluble alkaloids and Ginseng Radix et Rhizoma total ginsenosides compatibility on acute heart failure rats

BackgroundAconiti Lateralis Radix Praeparata has been used as the first cardiac drug over a 1000 years in Asian countries. Although most detoxification products are confirmed to be safe, the effect is not potent as desired. In previous study, we designed a one-step detoxification product by fresh cutting and continuously dried, which preserved more water-soluble alkaloids while eliminating toxicity. It is thus necessary to find more in vivo evidence to support its industrial development.MethodsInitially, network pharmacology was applied to analyze the related pathways of candidate components acting on heart failure diseases. Then, two heart failure models that were induced by propafenone hydrochloride and nimodipine (v/v, 1:1) and were given doxorubicin were carried out to test the cardiac activity. Moreover, the effect on mitochondrial energy metabolism was further assessed.ResultsNetwork pharmacology results indicated that Aconiti Lateralis Radix Praeparata treated heart failure through cAMP signaling pathway, calcium signaling pathway, adrenergic signaling in cardiomyocytes and so on. These pathways were highly correlated with myocardial contractility and mitochondrial energy metabolism. Trials on heart failure rats demonstrated that the novel processed-product could produce a stronger positive inotropic action and increase more Na+–K+–ATPase and Ca2+–Mg2+–ATPase than Heishunpian. Pathological results also revealed the novel one could better restore the morphology of cardiomyocytes and reduce vacuolar lesions. It also could inspire more energy with a lower concentration.ConclusionsThis study provides scientific evidence for the clinical application of new products. It is of great benefit to innovate the industrial detoxification process of Aconitum.

Impact of presence of excipients in drug analysis in fed-state gastric biorelevant media

Objective To analyze retrospectively the cardioversion for paroxysmal supraventricular tachycardia(PSVT) in emergency department in order to explore rational guidance for the diagnosis and treatment for PSVT. Methods A retrospective analysis of PSVT patients in the emergency department admitted from June 2015 to December 2015 was carried out. First, all the patients were divided into two groups according to the cardioversion achieved by Valsalva’s maneuvre or not. Forty patients were enrolled in study. There were 11 patients got cardioversion successfully achieved by the Valsalva’s maneuvre and 29 patients failed to get cardioversion. Then, comparisons of demographics, vital sign, serum CTNI, potassium and NTproBNP level were carried out between these groups of patients using statistical analysis. The categorical variable was expressed in percentage and the continuous variable was described by mean±standard deviation and the comparisons of parameters were conducted by group t-test and chi-square test. Results The success rate of PSVT maneuvre cardioversion was 27.5%. In addition, there were no significant differences in demographics vital sign, TNI and NTproBNP between the two groups while there were significant differences in serum potassium level between the two groups [(3.8±0.4)mmol/L vs. (3.5±0.35)mmol/L P<0.05]. There was no significant difference in successful rate of cardioversion between the standard Valsalva’s maneuvre(n=6) the modified Valsalva’s maneuvre(n=5). The second-line treatment mainly included propafenone, adenosine, electroversion, verapamil and amiodarone. The propafenone was the most common second-line agent used for PSVT cardioversion accounting for 58.6%. Conclusions The success rate of Valsalva’s maneuver cardioversion was low. Keeping properly a higher level of serum potassium could increase the success rate of cardioversion by Valsalva’s maneuvre. Key words: Paroxysmal supraventricular tachycardia; Manoeuvre cardioversion; Modified Valsalva Manoeuvre; Propafenone; Electroversion; CTNI; NTproBNP

Zingiberis rhizoma mediated enhancement of the pharmacological effect of aconiti lateralis radix praeparata against acute heart failure and the underlying biological mechanisms

The protective effects of compatibility of Aconiti Lateralis Radix Praeparata and Zingiberis Rhizoma on rats with heart failure by enhancing mitochondrial biogenesis via Sirt1/PGC-1α pathway

Highly sensitive UHPLC–MS/MS method for the simultaneous estimation of propafenone and its metabolites 5-hydroxypropafenone and N-depropylpropafenone on human dried blood spots technique and application to a pharmacokinetic study