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Journal of the American Society For... Feb 2022Combining solid phase microextraction (SPME) and mass spectrometry (MS) analysis has become increasingly important to many bioanalytical, environmental, and forensic...
Combining solid phase microextraction (SPME) and mass spectrometry (MS) analysis has become increasingly important to many bioanalytical, environmental, and forensic applications due to its simplicity, rapid analysis, and capability of reducing matrix effects for complex samples. To further promote the adoption of SPME-MS based analysis and expand its application scope calls for efficient and convenient interfaces that couple the SPME sample handling with the efficient analyte ionization for MS. Here, we report a novel interface that integrates both the desorption and the ionization steps in one device based on the capillary vibrating sharp-edge spray ionization (cVSSI) method. We demonstrated that the cVSSI is capable of nebulizing liquid samples in a pulled-tip glass capillary with a battery powered function generator. The cVSSI device allows the insertion of a SPME probe into the spray capillary for desorption and then direct nebulization of the desorption solvent in situ. With the integrated interface, we have demonstrated rapid MS analysis of drug compounds from serum samples. Quantitative determination of various drug compounds including metoprolol, pindolol, acebutolol, oxprenolol, capecitabine, and irinotecan was achieved with good linearity ( = 0.97-0.99) and limit of detection ranging from 0.25 to 0.59 ng/mL without using a high voltage source. Only 3.5 μL of desorption solvent and 3 min desorption time were needed for the present method. Overall, we demonstrated a portable SPME-MS interface featuring high sensitivity, short analysis time, small footprint, and low cost, which makes it an attractive method for many applications requiring sample cleanup including drug compound monitoring, environmental sample analysis, and forensic sample analysis.
Topics: Carbamazepine; Equipment Design; Limit of Detection; Metoprolol; Pindolol; Sensitivity and Specificity; Serum Albumin, Bovine; Solid Phase Microextraction; Spectrometry, Mass, Electrospray Ionization
PubMed: 35040644
DOI: 10.1021/jasms.1c00305 -
Annales Pharmaceutiques Francaises Sep 2021The aim of this study was to predict the plasma concentrations of acebutolol tablets with different dissolution profiles using computer modelling and evaluating whether...
PURPOSE
The aim of this study was to predict the plasma concentrations of acebutolol tablets with different dissolution profiles using computer modelling and evaluating whether they are bioequivalent using simulated population studies.
METHODS
The dissolution behaviour of acebutolol was studied in the USP Apparatus-II using different dissolution media for pH 1.2, 4.5, and 6.8 at 37±0.5°C. The obtained dissolution data, as well as plasma concentration-time data of the reference product from the literature were used as inputs to build pharmacokinetic model of acebutolol within GastroPlus™ software (version 9.7, Simulations Plus Inc., Lancaster, CA, USA) to simulate the in vivo profiles of the drug.
RESULTS
The dissolution profiles of the reference product Sectral® 400mg tablets and a locally produced generic product were>85% in 15min in three dissolution media. Simulation results demonstrated that the brand and generic products would show the same in vivo performance. Population simulation results of the ln-transformed 90% confidence interval for the ratio of C, AUC and AUC values for the two products were within the 80-125% interval, showing to be bioequivalent.
CONCLUSION
Based on the in vitro results combined with in silico simulations using GastroPlus™, a biowaiver for immediate release acebutolol tablets is justified. Furthermore, computer modelling has shown to be a very intersting tool to prove the bioequivalence for these products.
Topics: Acebutolol; Computer Simulation; Solubility; Tablets; Therapeutic Equivalency
PubMed: 33675740
DOI: 10.1016/j.pharma.2021.02.004 -
Frontiers in Cell and Developmental... 2022Female reproductive cycle, also known as menstrual cycle or estrous cycle in primate or non-primate mammals, respectively, dominates the reproductive processes in...
Female reproductive cycle, also known as menstrual cycle or estrous cycle in primate or non-primate mammals, respectively, dominates the reproductive processes in non-pregnant state. However, in addition to reproductive tissues, reproductive cycle could also perform global regulation because the receptors of two major female hormones fluctuating throughout the cycle, estrogen and progesterone, are widely distributed. Therefore, a multi-tissue gene expression landscape is in continuous demand for better understanding the systemic changes during the reproductive cycle but remains largely undefined. Here we delineated a transcriptomic landscape covering 15 tissues of C57BL/6J female mice in two phases of estrous cycle, estrus and diestrus, by RNA-sequencing. Then, a number of genes, pathways, and transcription factors involved in the estrous cycle were revealed. We found the estrous cycle could widely regulate the neuro-functions, immuno-functions, blood coagulation and so on. And behind the transcriptomic alteration between estrus and diestrus, 13 transcription factors may play important roles. Next, bioinformatics modeling with 1,263 manually curated gene signatures of various physiological and pathophysiological states systematically characterized the beneficial/deleterious effects brought by estrus/diestrus on individual tissues. We revealed that the estrous cycle has a significant effect on cardiovascular system (aorta, heart, vein), in which the anti-hypertensive pattern in aorta induced by estrus is one of the most striking findings. Inspired by this point, we validated that two hypotensive drugs, felodipine and acebutolol, could exhibit significantly enhanced efficacy in estrus than diestrus by mouse and rat experiments. Together, this study provides a valuable data resource for investigating reproductive cycle from a transcriptomic perspective, and presents models and clues for investigating precision medicine associated with reproductive cycle.
PubMed: 36589755
DOI: 10.3389/fcell.2022.983712 -
Chemosphere Jan 2022Acebutolol (ACE) has been widely used for the treatment of cardiovascular disorders, and its photochemical fate in natural waters is a matter of concern due to its...
Acebutolol (ACE) has been widely used for the treatment of cardiovascular disorders, and its photochemical fate in natural waters is a matter of concern due to its ubiquitous occurrence and its toxicity to aquatic organisms. In this study, the photodegradation of ACE in river water and synthetic waters were investigated under simulated sunlight irradiation. The results demonstrated that ACE photodegradation rate in river water was 3.2 times higher than that in pure water. Then the influences of HCO, NO and DOM on ACE photolysis were investigated under their concentrations similar with the ones in river water. ACE photodegradation was significantly enhanced in the presence of HCO alone, and the scavenging experiments and the electron paramagnetic resonance experiments together proved that HCO could be oxidized by triplet-excited state of ACE to generate CO, which subsequently played a key role in ACE degradation. The presence of both NO and DOM also increased the ACE photodegradation rates, and •OH and DOM* were found to be involved in the degradation. In addition, when DOM was added to a solution with HCO, the enhancement effect of HCO on ACE photodegradation was weakened due to the scavenging of CO by DOM combined with the light screening effect of DOM.
Topics: Acebutolol; Carbonates; Hydroxyl Radical; Photolysis; Water Pollutants, Chemical
PubMed: 34826949
DOI: 10.1016/j.chemosphere.2021.132318 -
Journal of Separation Science Jul 2023In the present study, five simple, feasible, and sensitive Ultra-high-speed liquid chromatography combined with mass spectrometry detection methods, using electrospray...
Ultra-high-speed liquid chromatography combined with mass spectrometry detection analytical methods for the determination of nitrosamine drug substance-related impurities.
In the present study, five simple, feasible, and sensitive Ultra-high-speed liquid chromatography combined with mass spectrometry detection methods, using electrospray ionization are proposed. These methods were developed and validated for the determination of four different nitrosamine drug substance-related impurities-N-nitrosoacebutolol, N-nitrosobisoprolol, N-nitrosometoprolol, and N-nitrososotalol-in five beta blockers active pharmaceutical ingredients-acebutolol HCl, bisoprolol fumarate, metoprolol tartrate, metoprolol succinate, and sotalol HCl. The proposed methods were validated as per regulatory guidelines. Acquity HSS T3 (3.0 × 100 mm, 1.8 μm) column and formic acid 0.1% in water combined with methanol or acetonitrile were used for chromatographic separation in all methods. The limit of detection and the limit of quantification were found to be in the range of 0.02-1.2 and 2-20 parts per billion, respectively. The accuracy and precision of the five methods have been demonstrated in the working range of each one, giving values of recovery within the range of 64.1%-113.3%, and the regression coefficients (R) were found to be in the range of 0.9978-0.9999. These methods could be used for controlling nitrosamine drug substance-related impurities content for beta blockers drug substances batches manufactured at Moehs group.
Topics: Chromatography, High Pressure Liquid; Mass Spectrometry; Adrenergic beta-Antagonists; Drug Contamination; Bisoprolol; Metoprolol
PubMed: 37070833
DOI: 10.1002/jssc.202300125 -
Forensic Science, Medicine, and... Oct 2023The objective of this study was to investigate the degradation pattern of cardiac troponin I in rats in vivo, and to determine whether the pattern was dependent on the...
The objective of this study was to investigate the degradation pattern of cardiac troponin I in rats in vivo, and to determine whether the pattern was dependent on the cause of death, for the purpose of estimating the postmortem interval. The rats were categorized into three distinct groups depending on the factors leading to their demise: the control group, the group experiencing acebutolol-induced cardiotoxicity, and the group affected by asphyxia. The analysis encompassed the isolation and segregation of the protein, subsequently employing Western blotting as a means of visualizing the results. The results revealed a distinct degradation pattern of cTnI into smaller fragments over time, indicating that cardiac troponin I can serve as a reliable marker for estimating the postmortem interval. Furthermore, noteworthy variations were noted in the degradation pattern of cardiac troponin I among the different causes of death, which suggests that this method can also be used to determine whether cardiac failure was the cause of death or not.
PubMed: 37804400
DOI: 10.1007/s12024-023-00719-x -
Journal of Chromatography. A Dec 2020The capability of liquid chromatography with microemulsions (MEs) as mobile phases was studied for the analysis of four parabens (butylparaben, ethylparaben,...
The capability of liquid chromatography with microemulsions (MEs) as mobile phases was studied for the analysis of four parabens (butylparaben, ethylparaben, methylparaben, and propylparaben) and seven β-adrenoceptor antagonists (acebutolol, atenolol, carteolol, metoprolol, oxprenolol, propranolol, and timolol). MEs were formed by mixing aqueous solutions of the anionic surfactant sodium dodecyl sulphate, the alcohol 1-butanol that played the role of co-surfactant, and octane as oil. In order to guarantee the formation of stable MEs, a preliminary study was carried out to determine the appropriate ranges of concentrations of the three components. For this purpose, mixtures of variable composition were prepared, and the possible separation of two phases (formation of an emulsion) was visually detected. The advantage offered by the addition of octane to micellar mobile phases, inside the concentration range that allows the formation of stable MEs, was evaluated by comparing the retention behaviour, peak profile and resolution of mixtures of the probe compounds, in the presence and absence of octane. The final aim of this work was the proposal of a mathematical equation to model the retention behaviour in microemulsion liquid chromatography. The derived global model that considered the three factors (surfactant, alcohol and oil) allowed the prediction of retention times at diverse mobile phase compositions with satisfactory accuracy (in the 1.1‒2.5% range). The behaviour was compared with that found with mobile phases without octane. The model also yielded information about the retention mechanism and revealed that octane, when inserted inside the micelle, modifies the interaction between solutes and micelles.
Topics: Butanols; Chromatography, Liquid; Emulsions; Micelles; Models, Chemical; Parabens; Sodium Dodecyl Sulfate; Surface-Active Agents; Water
PubMed: 33166895
DOI: 10.1016/j.chroma.2020.461651 -
Chemosphere Aug 2023Progress in excogitation suitable strategies for monitoring chemical compounds in wastewater is an essential step for further research into the occurrence, impact, and...
Progress in excogitation suitable strategies for monitoring chemical compounds in wastewater is an essential step for further research into the occurrence, impact, and fate of the pollutants in the aquatic environment. At present, it is desirable to advance and use economical, environmentally friendly and non-labour intensive methods of environmental analysis. In this study, carbon nanotubes (CNTs) were successfully applied, regenerated, and reused as a sorbent in passive samplers for monitoring contaminants in treated and untreated wastewater at three wastewater treatment plants (WWTPs) located in different urbanization areas in northern Poland. Three cycles of chemical and thermal regeneration of used sorbents were performed. It was shown that it is possible to regenerate CNTs a minimum of three times and reuse them in passive samplers while maintaining the desired sorption properties. The obtained results confirm that the CNTs are perfectly in line with the main principles of green chemistry and sustainability. Carbamazepine, ketoprofen, naproxen, diclofenac, p-nitrophenol, atenolol, acebutolol, metoprolol, sulfapyridine and sulfamethoxazole were detected in each of the WWTPs, both in treated and untreated wastewater. The obtained data drastically show the inefficiency of the removal of contaminants by conventional WWTPs. More importantly, the results even indicate negative contaminant removal in most cases, i.e. higher concentrations (up to 863%) of these substances in the effluent compared to the influent.
Topics: Wastewater; Nanotubes, Carbon; Environmental Monitoring; Water Pollutants, Chemical; Carbamazepine
PubMed: 37149101
DOI: 10.1016/j.chemosphere.2023.138855 -
Physical Chemistry Chemical Physics :... Jun 2016(14)N ultra-wideline (UW), (1)H{(15)N} indirectly-detected HETCOR (idHETCOR) and (15)N dynamic nuclear polarization (DNP) solid-state NMR (SSNMR) experiments, in...
(14)N ultra-wideline (UW), (1)H{(15)N} indirectly-detected HETCOR (idHETCOR) and (15)N dynamic nuclear polarization (DNP) solid-state NMR (SSNMR) experiments, in combination with plane-wave density functional theory (DFT) calculations of (14)N EFG tensors, were utilized to characterize a series of nitrogen-containing active pharmaceutical ingredients (APIs), including HCl salts of scopolamine, alprenolol, isoprenaline, acebutolol, dibucaine, nicardipine, and ranitidine. A case study applying these methods for the differentiation of polymorphs of bupivacaine HCl is also presented. All experiments were conducted upon samples with naturally-abundant nitrogen isotopes. For most of the APIs, it was possible to acquire frequency-stepped UW (14)N SSNMR spectra of stationary samples, which display powder patterns corresponding to pseudo-tetrahedral (i.e., RR'R''NH(+) and RR'NH2(+)) or other (i.e., RNH2 and RNO2) nitrogen environments. Directly-excited (14)N NMR spectra were acquired using the WURST-CPMG pulse sequence, which incorporates WURST (wideband, uniform rate, and smooth truncation) pulses and a CPMG (Carr-Purcell Meiboom-Gill) refocusing protocol. In certain cases, spectra were acquired using (1)H → (14)N broadband cross-polarization, via the BRAIN-CP (broadband adiabatic inversion - cross polarization) pulse sequence. These spectra provide (14)N electric field gradient (EFG) tensor parameters and orientations that are particularly sensitive to variations in local structure and intermolecular hydrogen-bonding interactions. The (1)H{(15)N} idHETCOR spectra, acquired under conditions of fast magic-angle spinning (MAS), used CP transfers to provide (1)H-(15)N chemical shift correlations for all nitrogen environments, except for two sites in acebutolol and nicardipine. One of these two sites (RR'NH2(+) in acebutolol) was successfully detected using the DNP-enhanced (15)N{(1)H} CP/MAS measurement, and one (RNO2 in nicardipine) remained elusive due to the absence of nearby protons. This exploratory study suggests that this combination of techniques has great potential for the characterization of solid APIs and numerous other organic, biological, and inorganic systems.
PubMed: 27314503
DOI: 10.1039/c6cp02855a -
Journal of Mass Spectrometry : JMS Dec 2023Beta blockers are a class of drugs commonly used to treat heart-related diseases; they are also regulated under the World Anti-Doping Agency. Tandem mass spectrometry is...
Beta blockers are a class of drugs commonly used to treat heart-related diseases; they are also regulated under the World Anti-Doping Agency. Tandem mass spectrometry is often used in the pharmaceutical industry, clinical analysis laboratory, and antidoping laboratory for detection and characterization of drugs and their metabolites. A deeper chemical understanding of dissociation pathways may eventually lead to an improved ability to predict tandem mass spectra of compounds based strictly on their chemical structure (or vice versa), which is especially important for characterization of unknowns such as emerging designer drugs or novel metabolites. In addition to providing insights into dissociation pathways, the use of energy-resolved breakdown curves can produce improved selectivity and lend insights into optimal fragmentation conditions for liquid chromatography-tandem mass spectrometry LC-MS/MS workflows. Here, we perform energy-resolved collision cell and multistage ion trap collision-induced dissociation-mass spectrometry (CID-MS) experiments, along with complementary density functional theory calculations, on five beta blockers (acebutolol, atenolol, bisoprolol, carteolol, and labetalol), to better understand the details of the pathways giving rise to the observed MS/MS patterns. Results from this work are contextualized within previously reported literature on these compounds. New insights into the formation of the characteristic product ion m/z 116 and the pathway leading to characteristic loss of 77 u are highlighted. We also present comparisons of breakdown curves obtained via qToF, quadrupole ion trap, and in-source CID, allowing for differences between the data to be noted and providing a step toward allowing for improved selectivity of breakdown curves to be realized on simple instruments such as single quadrupoles or ion traps.
Topics: Tandem Mass Spectrometry; Bisoprolol; Carteolol; Labetalol; Chromatography, Liquid; Acebutolol; Atenolol
PubMed: 37990768
DOI: 10.1002/jms.4985