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Journal of Chromatography. B,... Jul 2024Single-pass intestinal perfusion (SPIP) method is a widely used experimental model to determine the intestinal permeability of drugs. These studies are performed in the...
Single-pass intestinal perfusion (SPIP) method is a widely used experimental model to determine the intestinal permeability of drugs. These studies are performed in the presence of a reference standard (metoprolol, MT) and a zero permeability marker (phenol red, PR). Therefore, it is important to develop a validated method for simultaneous determination of the investigated compound along with MT and PR. The aim of this study was to develop a reversed phase high-performance liquid chromatography (RP-HPLC) method with UV-detection for the simultaneous determination of atenolol (ATN), MT, and PR in the perfusion medium used in SPIP experiments. Separation of compounds were performed using an InertSustain C18 (250 × 4.6 mm, 5 µm) HPLC column at 35 °C. The mobile phase was a mixture of acetonitrile and phosphate buffer (pH 7.0, 12.5 mM) in gradient elution, and was delivered at a flow rate of 1 mL/min. The acetonitrile ratio of the mobile phase increased linearly from 10 to 35 % over 15 min. The injection volume was 20 µL, and ATN, MT and PR were detected at 224 nm. The retention times under optimum HPLC conditions were 5.028 min, 12.401 min, and 13.507 min for ATN, MT and PR, respectively. The developed RP-HPLC method was validated for selectivity, specificity, calibration curve and range, accuracy and precision, carry-over effect, stability, reinjection reproducibility, recovery and robustness. The method was linear for ATN (0.76-50 μg/mL), MT (1.14-50 μg/mL), and PR (0.47-20 μg/mL) with determination coefficients of 0.9999, 0.9994 and 0.9998, respectively. The results obtained for all validation parameters of the developed RP-HPLC method met the required limits of the ICH M10 Guideline.
Topics: Chromatography, High Pressure Liquid; Animals; Atenolol; Metoprolol; Rats; Chromatography, Reverse-Phase; Reproducibility of Results; Linear Models; Phenolsulfonphthalein; Male; Limit of Detection; Rats, Wistar; Perfusion
PubMed: 38781808
DOI: 10.1016/j.jchromb.2024.124160 -
Journal of the American Society For... Jun 2024We investigated the applicability of proton transfer reaction-time-of-flight mass spectrometry (PTR-TOF-MS) for quantitative analysis of mixtures comprising glycerin,...
We investigated the applicability of proton transfer reaction-time-of-flight mass spectrometry (PTR-TOF-MS) for quantitative analysis of mixtures comprising glycerin, acetol, glycidol, acetaldehyde, acetone, and propylene glycol. While PTR-TOF-MS offers real-time simultaneous determination, the method selectivity is limited when analyzing compounds with identical elemental compositions or when labile compounds present in the mixture produce fragments that generate overlapping ions with other matrix components. In this study, we observed significant fragmentation of glycerin, acetol, glycidol, and propylene glycol during protonation via hydronium ions (HO). Nevertheless, specific ions generated by glycerin (/ 93.055) and propylene glycol (/ 77.060) enabled their selective detection. To thoroughly investigate the selectivity of the method, various mixtures containing both isotope-labeled and unlabeled compounds were utilized. The experimental findings demonstrated that when samples contained high levels of glycerin, it was not feasible to perform time-resolved analysis in HO mode for acetaldehyde, acetol, and glycidol. To overcome the observed selectivity limitations associated with the HO reagent ions, alternative ionization modes were investigated. The ammonium ion mode proved appropriate for analyzing propylene glycol (/ 94.086) and acetone (/ 76.076) mixtures. Concerning the nitric oxide mode, specific / were identified for acetaldehyde (/ 43.018), acetone (/ 88.039), glycidol (/ 73.028), and propylene glycol (/ 75.044). It was concluded that considering the presence of multiple product ions and the potential influence of other compounds, it is crucial to conduct a thorough selectivity assessment when employing PTR-TOF-MS as the sole method for analyzing compounds in complex matrices of unknown composition.
Topics: Mass Spectrometry; Volatile Organic Compounds; Electronic Nicotine Delivery Systems; Nicotiana; Propylene Glycol; Acetaldehyde; Acetone; Glycerol; Hot Temperature; Epoxy Compounds; Propanols
PubMed: 38780179
DOI: 10.1021/jasms.4c00062 -
Journal of Cytology 2024Rapidity and reliability are the major advantages of cytopathology in tumor diagnosis. The need for minimal turnaround time for assessing cytological smears has...
BACKGROUND
Rapidity and reliability are the major advantages of cytopathology in tumor diagnosis. The need for minimal turnaround time for assessing cytological smears has encouraged innovations in staining techniques that require lesser staining time with unequivocal cell morphology. Rapid Pap staining was introduced as a hybrid to conventional Pap stain. It improves staining quality, gets over the staining time in restriction, and is a more efficient technique financially. In the present study, a modified staining technique was adopted where phloxine is added as one of the cytoplasmic stain components in rapid Pap stain kits.
OBJECTIVE
The aim of this study was to assess whether the modification of the existing procedure by adding phloxine as one of the components of the cytoplasmic stain intensifies the cytoplasmic differentiation and cytoplasmic staining in gynecological smears.
MATERIALS AND METHODS
This was a prospective study done on 50 cases of gynecological smears. Two smears were collected from each patient and fixed in 100% propanol and stained with the rapid Pap stain kit procedure and modified rapid Pap stain with phloxine. Slides were then analyzed by two pathologists blinded to the staining method used. Five parameters were considered and scored (background, cell morphology, nuclear staining, cytoplasmic differentiation, and cytoplasmic staining). The quality index for each method was calculated by finding out the ratio of the actual score obtained to the maximum score possible.
RESULTS
Both the staining methods had comparable results. For both pathologists, the quality index calculated for modified Pap stain was found to be marginally higher than the quality index for rapid Pap. The mean quality index was comparable for modified Pap (0.91) and rapid Pap (0.89).
CONCLUSIONS
The efficacy of modified Pap stain with phloxine to distinctly stain the cytoplasm is comparable with that of rapid Pap stain. In addition, the intensity of staining can be enhanced with little cost outlay, and this can be especially beneficial in low-resource settings.
PubMed: 38779599
DOI: 10.4103/joc.joc_24_23 -
F1000Research 2023In the current work, co-rotating twin-screw processor (TSP) was utilized to formulate solid crystal suspension (SCS) of carvedilol (CAR) for enhancing its solubility,...
Co-rotating twin screw process for continuous manufacturing of solid crystal suspension: A promising strategy to enhance the solubility, permeation and oral bioavailability of Carvedilol.
In the current work, co-rotating twin-screw processor (TSP) was utilized to formulate solid crystal suspension (SCS) of carvedilol (CAR) for enhancing its solubility, dissolution rate, permeation and bioavailability using mannitol as a hydrophilic carrier. molecular dynamics (MD) studies were done to simulate the interaction of CAR with mannitol at different kneading zone temperatures (KZT). Based on these studies, the optimal CAR: mannitol ratios and the kneading zone temperatures for CAR solubility enhancement were assessed. The CAR-SCS was optimized utilizing Design-of-Experiments (DoE) methodology using the Box-Behnken design. Saturation solubility studies and dissolution studies were performed for all the formulations. Physicochemical characterization was performed using differential scanning calorimetry , Fourier transform infrared spectroscopy, X-ray diffraction studies, and Raman spectroscopy analysis. permeation studies and pharmacokinetic studies for the CAR-SCS were performed. Stability studies were performed for the DoE-optimized CAR-SCS at accelerated stability conditions at 40 ºC/ 75% RH for three months. Experimentally, the formulation with CAR: mannitol ratio of 20:80, prepared using a KZT of 120 ºC at 100 rpm screw speed showed the highest solubility enhancement accounting for 50-fold compared to the plain CAR. Physicochemical characterization confirmed the crystalline state of DoE-optimized CAR-SCS. dissolution studies indicated a 6.03-fold and 3.40-fold enhancement in the dissolution rate of optimized CAR-SCS in pH 1.2 HCl solution and phosphate buffer pH 6.8, respectively, as compared to the pure CAR. The enhanced efficacy of the optimized CAR-SCS was indicated in the and pharmacokinetic studies wherein the apparent permeability was enhanced 1.84-fold and bioavailability enhanced 1.50-folds compared to the plain CAR. The stability studies showed good stability concerning the drug content. TSP technology could be utilized to enhance the solubility, bioavailability and permeation of poor soluble CAR by preparing the SCS.
Topics: Carvedilol; Solubility; Biological Availability; Animals; Administration, Oral; Carbazoles; Propanolamines; Permeability; Male; Mannitol; Suspensions; Molecular Dynamics Simulation; Rats
PubMed: 38778814
DOI: 10.12688/f1000research.139228.1 -
Spectrochimica Acta. Part A, Molecular... Oct 2024Simultaneous determination of atenolol (ATN), losartan potassium (LOS), and hydrochlorothiazide (HCZ) in presence of HCZ impurity B was conducted by chemometric...
Resolution of overlapping spectra using chemometric manipulations of UV-spectrophotometric data for the determination of Atenolol, Losartan, and Hydrochlorothiazide in pharmaceutical dosage form.
Simultaneous determination of atenolol (ATN), losartan potassium (LOS), and hydrochlorothiazide (HCZ) in presence of HCZ impurity B was conducted by chemometric approaches and radial basis function network (RBFN) using UV-spectrophotometry without preliminary separation. Three chemometric models namely, classical least-squares (CLS), principal component regression (PCR), and partial least-squares (PLS) along with RBFN were utilized using the ternary mixtures of the three drugs. The multivariate calibrations were obtained by measuring the zero-order absorbance of the mixtures from 250 to 270 nm at the interval of 0.2 nm. The models were built covering the concentration range of (4.0 to 20.0), (3.8 to 20.2), and (0.9 to 50.1) μg mL for ATN, LOS, and HCZ, respectively. The regression coefficient was calculated between the actual and predicted concentrations of the 3 drugs using CLS, PCR, PLS and RBFN. The accuracy of the developed models was evaluated using the root mean square error of prediction (RMSEP) giving satisfactory results. The proposed methods were simple, accurate, precise and were applied efficiently for the quantitation of the three components in laboratory-prepared mixtures, and in dosage form showing good recovery values. In addition, the obtained results were compared statistically with each other using ANOVA test showing non-significant difference between them.
Topics: Hydrochlorothiazide; Atenolol; Losartan; Spectrophotometry, Ultraviolet; Least-Squares Analysis; Principal Component Analysis; Dosage Forms; Reproducibility of Results
PubMed: 38776669
DOI: 10.1016/j.saa.2024.124471 -
RSC Advances May 2024Gas monitoring devices are in demand for a rapidly growing range of applications. Metal oxide-based gas sensors have been extensively used for the detection of toxic...
Gas monitoring devices are in demand for a rapidly growing range of applications. Metal oxide-based gas sensors have been extensively used for the detection of toxic pollutant gases, combustible gases, and hydrocarbon vapors. The sensitivity for a low concentration and observed response and the recovery times of the reported gas sensors are not satisfactory, and it needs further detailed studies. In the present work, undoped SnO and cadmium sulfide (CdS)-doped SnO thick films were fabricated using the screen-printing method to study their sensing behavior towards tested organic vapors such as acetone, propanol, and ethanol. The sensing properties of fabricated sensors were investigated for the test gases, acetone, propanol, and ethanol, at an elevated temperature of 473 K. It was observed that the 2 wt% CdS-doped SnO sensor showed a maximum response (78%) and was highly selective (44.6%) to propanol over acetone and ethanol. The results showed that the diminution of the SnO crystallite size with the CdS content leads to an improvement in the response of the SnO sensor for the tested gases. The microstructural properties are also correlated to the sensing behavior. The measurement showed that the CdS-SnO thick film sensor is highly sensitive. At the same time, it is more selective to propanol than the other test gases, ethanol and acetone.
PubMed: 38774622
DOI: 10.1039/d4ra01888e -
ChemSusChem May 2024The efficient acetate conversion from CO electroreduction is challenging due to the poor selectivity at high reaction rate, which requires the competition with H and...
The efficient acetate conversion from CO electroreduction is challenging due to the poor selectivity at high reaction rate, which requires the competition with H and other C (i. e., ethylene, ethanol, n-propanol) reduction products. Electrolyte engineering is one of the efficient strategies to regulate the reaction microenvironment. In this work, the adding of sulfite (SO ) with high nucleophilicity in KOH electrolytes was demonstrated to enable improving the CO-to-acetate conversion via generating a S-O chemical bond between SO and oxygenated *C intermediates (i. e., *CO-CO, *CO-COH) compared with that in pure KOH system on both synthesized Cu(200)- and normal commercial Cu(111)-facets-exposed metallic Cu catalysts. As a result, the prepared Cu(200)-facets-exposed metallic Cu catalyst with surface ions modification showed an superior Faradaic efficiency of 63.6 % at -0.6 A ⋅ cm, and extraordinary absolute value of peak partial current density as high as 1.52 A ⋅ cm with adding SO in KOH electrolytes, compared to the best reported values in both CO and CO electroreduction. Our work suggests an attractive strategy to introduce the oxyanion with high nucleophilicity in electrolytes to regulate the microenvironment for industrial-current-density electrosynthesis of acetate from CO electroreduction.
PubMed: 38769898
DOI: 10.1002/cssc.202400683 -
ACS Omega May 2024The solubility of eplerenone (EP) in 13 pure solvents (acetonitrile, ,-dimethylformamide (DMF), acetone, 2-butanone, 4-methyl-2-pentanone, ethyl formate, methyl acetate,...
The solubility of eplerenone (EP) in 13 pure solvents (acetonitrile, ,-dimethylformamide (DMF), acetone, 2-butanone, 4-methyl-2-pentanone, ethyl formate, methyl acetate, ethyl acetate, propyl acetate, butyl acetate, methyl propionate, ethyl propionate, ethanol, and 1-propanol) was determined by the gravimetric method at atmospheric pressure and various temperatures (from 283.15 to 323.15 K). The results showed that the solubility of EP in the selected solvents was positively correlated with the thermodynamic temperature, and the order of solubility of EP at 298.15 K was acetonitrile > DMF > 2-butanone > methyl acetate > 4-methyl-2-pentanone > methyl propionate > ethyl acetate > propyl acetate > ethyl formate > acetone > butyl acetate > ethanol >1-propanol. The modified Apelblat model, van't Hoff model, λ model, and polynomial empirical model were used for fitting the solubility data, and then the λ model was found to have the highest fitting accuracy with a minimum ARD of 7.0 × 10 and a minimum RMSD of 6.1 × 10. The solvent effect between the solute and the solvent was analyzed using linear solvation energy relationship (LSER), and the enthalpy of solvation (Δ), entropy of solvation (Δ), and Gibbs free energy of solvation (Δ) of the dissolution process of EP were calculated by the van't Hoff model, which indicated that the dissolution process of EP in the selected solvents was endothermic, nonspontaneous, and entropy-increasing. In this work, the solubility, dissolution characteristics, and thermodynamic parameters of EP were studied, which will provide data support for the production, crystallization, and purification of EP and will provide important guidance for the crystallization optimization of EP in industry.
PubMed: 38764651
DOI: 10.1021/acsomega.4c01550 -
Heart & Lung : the Journal of Critical... 2024COVID patients continue to experience unremitting symptoms that extend far beyond the initial illness. While there is rapid accumulation of data on acute COVID treatment...
BACKGROUND
COVID patients continue to experience unremitting symptoms that extend far beyond the initial illness. While there is rapid accumulation of data on acute COVID treatment in hospitalized patients, little is known regarding post-COVID management.
OBJECTIVES
To describe our center's experience treating post-COVID sub-syndromes encountered in Post-COVID Lung Clinic.
METHODS
We retrospectively reviewed data on 98 post-COVID patients evaluated in our clinic between 07/01/2020-12/31/2022. We encountered three distinct post-COVID subtypes: 1) respiratory complaints associated with increased O2 requirements and abnormal CT findings (post-COVID interstitial lung disease [ILD]), 2) respiratory complaints associated with tachycardia (post-COVID dyspnea-tachycardia syndrome [DTS]). Post-COVID ILD patients (n = 28) received steroids in combination with cell cycle inhibitor (mycophenolate mofetil-MMF). Post-COVID DTS patients (n = 16) were treated with metoprolol. 3) A third, undifferentiated group presented with mild respiratory complaints and normal spirometry (n = 17) and was followed in clinic without initiation of a specific treatment.
RESULTS
In treated post-COVID ILD patients, mean oxygen requirements at rest (1.96 ± 1.79 L/NC) decreased to 0.89 ± 1.29 L/NC at 6 months follow-up, p = 0.005. In patients with post-COVID DTS, mean heart rate at rest decreased (98 ± 15 bpm to 79 ± 11 bpm) at 6 months follow-up, p = 0.023. 60 % of patients reported an improvement in exertional dyspnea.
CONCLUSIONS
Our descriptive study presents a single center outpatient COVID-19 clinic experience. We encountered 3 post-COVID sub-syndromes and describe their treatments: post-COVID interstitial lung disease [ILD] treated with a novel regimen of MMF and steroids, post COVID dyspnea-tachycardia syndrome [DTS] treated with metoprolol, and a third subgroup with mild undifferentiated symptoms without specific treatment.
Topics: Humans; COVID-19; Male; Female; Retrospective Studies; Middle Aged; Aged; Dyspnea; SARS-CoV-2; Lung Diseases, Interstitial; Ambulatory Care; Tachycardia; Post-Acute COVID-19 Syndrome; Metoprolol
PubMed: 38759575
DOI: 10.1016/j.hrtlng.2024.05.004 -
BMC Veterinary Research May 2024Gray horses are predisposed to equine malignant melanoma (EMM) with advancing age. Depending on the tumor's location and size, they can cause severe problems (e.g.,... (Comparative Study)
Comparative Study
Potent drug delivery enhancement of betulinic acid and NVX-207 into equine skin in vitro - a comparison between a novel oxygen flow-assisted transdermal application device and microemulsion gels.
BACKGROUND
Gray horses are predisposed to equine malignant melanoma (EMM) with advancing age. Depending on the tumor's location and size, they can cause severe problems (e.g., defaecation, urination, feeding). A feasible therapy for EMM has not yet been established and surgical excision can be difficult depending on the location of the melanoma. Thus, an effective and safe therapy is needed. Naturally occurring betulinic acid (BA), a pentacyclic triterpene and its synthetic derivate, NVX-207 (3-acetyl-betulinic acid-2-amino-3-hydroxy-2-hydroxymethyl-propanoate) are known for their cytotoxic properties against melanomas and other tumors and have already shown good safety and tolerability in vivo. In this study, BA and NVX-207 were tested for their permeation potential into equine skin in vitro in Franz-type diffusion cell (FDC) experiments after incubation of 5 min, 30 min and 24 h, aiming to use these formulations for prospective in vivo studies as a treatment for early melanoma stages. Potent permeation was defined as reaching or exceeding the half maximal inhibitory concentrations (IC) of BA or NVX-207 for equine melanoma cells in equine skin samples. The active ingredients were either dissolved in a microemulsion (ME) or in a microemulsion gel (MEG). All of the formulations were transdermally applied but the oil-in-water microemulsion was administered with a novel oxygen flow-assisted (OFA) applicator (DERMADROP TDA).
RESULTS
All tested formulations exceeded the IC values for equine melanoma cells for BA and NVX-207 in equine skin samples, independently of the incubation time NVX-207 applied with the OFA applicator showed a significant time-dependent accumulation and depot-effect in the skin after 30 min and 24 h (P < 0.05).
CONCLUSIONS
All tested substances showed promising results. Additionally, OFA administration showed a significant accumulation of NVX-207 after 30 min and 24 h of incubation. Further in vivo trials with OFA application are recommended.
Topics: Animals; Horses; Betulinic Acid; Pentacyclic Triterpenes; Triterpenes; Administration, Cutaneous; Emulsions; Skin; Drug Delivery Systems; Gels; Melanoma; Oxygen; Skin Absorption; Horse Diseases; Propanolamines
PubMed: 38755639
DOI: 10.1186/s12917-024-04064-1