Negative Ion Research Articles

A simple and sensitive LC-MS/MS method for the determination of loganic acid in rat plasma and its pharmacokinetic analysis.

Loganic acid is an iridoid compound extracted from Gentianaceae plant Gentiana macrophylla Pall. It can effectively inhibit inflammation and tumor migration and has antioxidant activity. In this paper, we establish a simple, fast, sensitive and validated LC-MS method with the purpose of quantification of loganic acid in rat plasma with gliclazide as an internal standard (IS). Methanol was used to precipitate the protein in the plasma sample, and a C18 column (2.1 × 50 mm, 1.7μm) was used for the separation of the target compound. Meanwhile, 0.1% formic acid water-methanol was employed as the mobile phase. Multiple reaction monitoring detection mode was adopted in detection with m/z 375.1 > 213.2 for loganic acid and m/z 322.1 > 169.9 for the IS, respectively, in negative ion scan mode. The linear range of calibration curve was 5.77-11,540.00 ng/ml, and the lower limit of detedtion was 2.89 ng/ml. The inter-day and intra-day precision and accuracy were <15% for lower limit of quantitation, low, middle and high quality control samples. This method was successfully used for the pharmacokinetic study of loganic acid in rat plasma at a dose range of 50-150 mg/kg for oral administration and 2mg/kg for intravenous administration. The pharmacokinetic results showed that the oral bioavailability of loganic acid was low (2.71-5.58%).

The detachment-induced mode in electronegative capacitively coupled radio-frequency plasmas

Insights into the spatio-temporally resolved electron power absorption dynamics in capacitively coupled radio-frequency plasmas are essential for understanding the fundamentals of their operation and as a basis for knowledge-based plasma process development. Similar to the γ-mode, an ionization maximum is observed at the sheath edge around the time of maximum sheath voltage in electronegative oxygen discharges at a pressure of 300 Pa. Based on Particle-in-Cell/Monte Carlo Collisions (PIC/MCC) simulations, we demonstrate that this maximum is not only caused by secondary electrons emitted at the electrode and collisionally multiplied inside the sheath. In fact, it also occurs in the complete absence of secondary electrons in the simulation, and is caused by the generation of O− ions by electron attachment close to the electrode during the local sheath collapse. These negative ions are accelerated towards the plasma bulk by the sheath electric field during sheath expansion. By electron detachment from these negative ions, electrons are generated inside the sheath and are accelerated towards the plasma bulk by the instantaneous sheath electric field—similarly to secondary electrons. Ionization is also observed in the plasma bulk and caused by electrons generated by detachment and accelerated by the high drift-and ambipolar electric fields. This detachment-induced electron power absorption is found to have significant effects on the discharge in the presence and absence of secondary electron emission. Its fundamentals are understood based on an analysis of the spatio-temporal electron and O− power absorption dynamics as well as the trajectory of selected O− ions close to the electrode.

Characteristics of a hybrid radio frequency capacitively and inductively coupled plasma using hydrogen gas

A hybrid combination of a radio frequency (RF) capacitively coupled plasma (CCP) equipped with a ring-shaped hollow powered electrode and an inductively coupled plasma (ICP) with a helical antenna is investigated in hydrogen gas. Characteristics of the RF hybrid plasma are measured by a Langmuir probe at a fixed position in the center between the RF powered and grounded electrode for various CCP powers of 50–150 W. The voltage drop across the CCP is found to be almost independent of the ICP power. The RF hybrid plasma attains a high ion density of the order of 1010 cm−3 between the electrodes even at a low CCP input power of 50 W. The plasma density is strongly affected by the CCP generator power, while the floating potential is controlled by the ICP power, whereas the electron temperature is independent of the ICP power for various CCP powers. The negative ion production is enhanced by increasing the ICP power, resulting in a decrease in the ratio of the negative to the positive charge saturation current detected by the Langmuir probe. The maximum ratio of the negative ion density to the electron density is approximately 8 at a CCP power of 50 W and an ICP power of 250 W.

In vitro antioxidant and antibacterial activities of aqueous extract of microalgae strain MRB-1, MRB-2, and MRB-3

Abstract The awareness growth of human health encourages market demand of functional food. Microalgae are promoted as natural resources for functional food, food additives and food preservatives, considering their metabolites and nutrient-rich components with diverse pharmacological activities. This study aims to evaluate the phytochemicals, antioxidant, and antibacterial activities of aqueous extracts of microalgae strain MRB-1, MRB-2, and MRB-3. The morphological surface of microalgae cells was analyzed using Scanning Electron Microscopy (SEM). The metabolites of the extract were conducted using Liquid Chromatography-High Resolution Mass Spectroscopy (LC-HRMS) with positive and negative ion modes. In addition, the antioxidant activity was evaluated using a 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay and the antibacterial activity was assessed using the agar disk-diffusion method against gram-positive bacteria (Staphylococcus aureus ATCC 25923) and gram-negative bacteria (Escherichia coli ATCC 8739). The total phenolic contents (TPC) of the extract was determined using the Folin-Ciocalteu assay. The result revealed that the aqueous extract of microalgae strain MRB-1 had the highest scavenging activity toward DPPH radicals with a value of 24.33±1.44% at 0.8 mg/mL. This data was in accordance with the TPC of the extract, whereas the highest TPC was also obtained from strain MRB-1 extract (17.73±0.64 mg GAE/g extract). Meanwhile, the MRB-2 extract had the highest inhibition activity against S. aureus, with a value of 11.78±2.06 mm at 18 mg/mL. The results of this study indicated that microalgae from the peatlands potentially benefit to human health as a natural antioxidant and antibacterial source.

Identification of chemical components in Qinggu San reference sample of classial prescription based on UHPLC-Q/Orbitrap HRMS combined with molecular network technology

The method of ultra-high performance liquid chromatography-quadrupole-electrostatic field orbitrap high-resolution mass spectrometry(UHPLC-Q/Orbitrap HRMS)combined with molecular network was developed in this study for rapidly analyzing the chemical components of the Qinggu San reference sample of classical prescription. Firstly, an ACQUITY UPLC BEH Shield RP_(18) column(2.1 mm×100 mm, 1.7 μm)was used, and acetonitrile and 0.1% formic acid were taken as the mobile phases for gradient elution. The flow rate was 0.4 mL·min~(-1), and the column temperature was 30 ℃. Under these conditions, the mass spectrum data were collected in both positive and negative ion modes of the heated electrospray ionization source. Subsequently, the mass spectrum data of the Qinggu San reference sample were uploaded to the Global Natural Products Social Molecular Network(GNPS)platform for calculation and analysis, and a visual molecular network was built with Cytoscape 3.8.2 software. On this basis, the chemical components of the Qinggu San reference sample were identified by fragmentation regularity of standard compounds, retention time, accurate relative molecular weight of HR-MS, characteristic fragment ions information, literature, and databases. Finally, a total of 105 chemical components were identified and speculated in the Qinggu San reference sample, including 19 iridoid glycosides, 23 flavonoids, 15 phenylpropanoids, 11 triterpene saponins, and 37 other components. Meanwhile, two of these components are potential new compounds. The method used in this study not only achieved rapid and accurate identification of chemical components in the Qinggu San reference sample and provided a scie-ntific basis for the study of pharmacological substances and quality control of Qinggu San compound preparations but also provided a refe-rence for the rapid identification of chemical components in traditional Chinese medicine compound preparations.

Metabolite identification and metabolic pathway analysis of Platycodonis Radix extracts from Tongcheng city in rats

In this study, we delved into the prototypical components and metabolites of Platycodonis Radix extracts(PRE) from Tongcheng city in plasma, urine and feces of rats, and revealed its metabolic pathways and metabolic rules in vivo. The prototypical components and metabolites of PRE in rats were characterized and identified by ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS) and mass defect filter(MDF). The biological samples were analyzed by ACQUITY UPLC BEH C_(18)(2.1 mm×100 mm, 1.7 μm), with 0.1% formic acid water(A)-0.1% formic acid acetonitrile(B) as mobile phase, and the biological samples were analyzed in negative ion mode by electrospray ionization mass spectrometry(ESI-MS). Twelve prototypical saponins and twenty-seven metabolites were detected in plasma, urine and feces of rats treated with PRE by oral administration. Eleven prototypical components and nine metabolites were detected in plasma, eleven prototypical components and eight metabo-lites were detected in urine, and ten prototypical components and twenty metabolites were detected in feces. Further studies showed that the metabolic pathways of PRE in rats mainly include oxidation, reduction, acetylation, stepwise hydrolytic deglycosylation, glucuronidation and so on. This study provides a scientific basis for clarifying the pharmacological basis and mechanism of PRE from Tongcheng city.

The cervicovaginal metabolome in women with favorable induction cervix and those unfavorable for induction when delivering at term

BackgroundCervical ripening is crucial for induction. However, its influencing factors, mechanistic understanding, and effective risk stratification are still challenging. Recent research suggested that microorganisms and their metabolites in vaginal spaces correlate to preterm birth. However, it remains unclear whether the cervicovaginal metabolome is related to the natural physiological process of cervical maturation. ObjectiveWe aimed to analyze the cervicovaginal metabolome in women with favorable induction cervix and those unfavorable for induction when delivering at term. Study designCervicovaginal swabs were collected between 40 and 41 weeks gestation from the following 2 different groups of patients: Ripe group (n = 25) which was favorable for the induction cervix and Unripe group which was unfavorable for the induction cervix (n = 25). Samples were tested using untargeted metabolomics analysis and analyzed by a bioinformatics platform. The correlation analysis between the metabolome and the previously acquired microbiome was also performed. ResultsA total of 629 metabolites were identified in cervicovaginal fluid. The cervicovaginal metabolome was significantly different between the women with the ripe cervix and those with the unripe cervix, especially within each stratum of the same CST. Metabolites within the amino acid, carbohydrate, and dipeptide pathways may play a role in this distinction. Thirty-four metabolites were significantly upregulated, and the remaining fourteen were significantly downregulated in the Unripe group with an unripe cervix unfavorable for induction. Statistical modeling identified Arachidonic Acid and Nicotinate associated with the risk of cervical maturation disorder (AUC 0.87) in negative ion mode. A combination of Choline and d-Mannose identified a risk of cervical maturation disorder (AUC 0.80) in positive ion mode, improved by Lactobacillus relative abundance (AUC 0.89). ConclusionThese data suggested that the cervicovaginal space was metabolically active during pregnancy and significantly altered among the women with the mature and immature cervix. Combining the genera-level phylotypes and metabolites could build better cervix maturity prediction models. By using cervicovaginal fluid samples, we demonstrated the potential of multi-data type integration for developing composite models toward understanding the contribution of the vaginal environment to the remodeling of cervix during term pregnancy.

Nonlinear propagation of ion-acoustic waves along with their bifurcation analysis in a negative ion plasma in the presence of quartic nonlinearity

In this article, the propagation of ion-acoustic shock and periodic waves along with their dynamical analysis around the supercritical values is studied in a (1 + 1)-dimensional collisionless negative ions plasma system comprising of inertia SF 6− with mass m−i and temperature T−i, inertia K+ with mass m+i and temperature T+i and inertialess non-extensive distributed electrons. By considering the appropriate starching coordinates and expansion of perturbation quantities, the Burgers-type equation with quartic nonlinearity is derived. Using the traveling wave transformation, a planar dynamical system is formed. The phase portrait is drawn and the associated nonlinear waves are analyzed. The research presented could be beneficial for understanding and forecasting localized electrostatic disturbances in the F- and D-layers of Earth's ionosphere as well as for guiding future experimental investigations in plasma laboratories.

Determination of warfarin in volumetric absorptive microsampling by liquid chromatography-tandem mass spectrometry

ObjectiveThis study aims to develop and validate bioanalytical method for quantifying warfarin in VAMS samples using liquid chromatography tandem mass spectrometry (LC-MS/MS), directly implementing the method to patients receiving warfarin therapy. MethodsThe UPLC-MS/MS method was developed and optimized, with quercetin as the internal standard. Sample preparation was carried out using protein precipitation with methanol-acetonitrile (1:3 v/v). ResultsChromatographic separation was achieved using Acquity® UPLC BEH C18 column with 0.1 % formic acid-acetonitrile-methanol (30:69:1 v/v) as mobile phase, in isocratic elution. Multiple Reaction Monitoring (MRM) detection was done using m/z values of 307.10 → 161.06 for warfarin and 301.03 → 150.98 for quercetin as internal standard, using Electrospray Ionization (ESI) negative ion source. The clinical application of the bioanalytical method was carried out on 25 patients receiving warfarin therapy at Universitas Indonesia Hospital and warfarin levels were well within the calibration range from 6.05 to 431.39 ng/mL. ConclusionA novel method has been developed to analyze warfarin in VAMS samples. This method has been fully validated according to guideline from FDA 2022 and is linear in the range of 5–500 ng/mL and the value of r ≥ 0.9977, and successfully applied for the analysis of warfarin in VAMS samples of clinical patients.

On the positron-acoustic Kawahara solitary and cnoidal waves in a non-Maxwellian electron–positron–ion plasma

The dissemination of positron-acoustic (PA) nonlinear structures, including the solitary waves (SWs) and cnoidal waves (CWs), is analyzed in an unmagnetized electron–positron–ion (e–p–i) plasma having inertial cold positrons and inertialess Cairns distributed electrons and Maxwellian positrons as well as immobile positive ions. The reductive perturbation method (RPM) is introduced to reduce the fluid equations to this model to the Korteweg–de Vries (KdV) type equation for studying small amplitude PA waves (PAWs). Moreover, the Kawahara (sometimes called the fifth-order KdV) equation is also obtained to investigate the characteristics of large amplitude PAWs. The effects of related parameters, such as nonthermal parameters, hot positron concentration, electron concentration, and temperature ratios, are numerically examined on the features of SWs and CWs.

Pharmacokinetics of Anti-rheumatic Drugs Methotrexate and Tofacitinib with its Metabolite M9 in Rats by UPLC-MS/MS.

Tofacitinib is an oral JAK inhibitor for the treatment of rheumatoid arthritis (RA). The clinical efficacy and safety of an administered tofacitinib, either monotherapy or in combination with conventional synthetic disease-modifying anti-rheumatic drugs, mainly methotrexate (MTX), have been evaluated. The high plasma concentration with delayed medicine clearance may affect the liver and/or kidney functions. In this study, an ultra-performance liquid chromatography-tandem mass spectrometry (UPLC- MS/MS) method for the quantitative analysis of methotrexate, tofacitinib, and metabolite M9 in plasma of Sprague Dawley (SD) rats was developed, and its effectiveness was validated as well. Methotrexate, tofacitinib, M9 and fedratinib (internal standard, IS) were separated by gradient elution. The chromatography was performed on an Acquity BEH C18 (2.1 mm × 50 mm, 1.7 μm) column with the mobile phases of acetonitrile and 0.1% formic acid aqueous solution with different proportions at the flow rate of 0.30 mL/min. In the positive ionization mode, the analyzes were detected using a Xevo TQ-S triple quadrupole tandem mass spectrometer, with the following mass transition pairs: m/z 313.12 → 148.97 for tofacitinib, m/z 329.10 → 165.00 for M9 and m/z 455.12 → 308.05 for methotrexate. The obtained results manifested good calibration linearity over the ranges of tofacitinib at 0.1-100 ng/mL, M9 at 0.05-100 ng/mL, and methotrexate at 0.05-100 ng/mL. The lower limit of quantifications (LLOQs) of methotrexate, tofacitinib and M9 were 0.05 ng/mL, 0.1 ng/mL and 0.05 ng/mL, respectively. Intra-day and inter-day accuracy values were confirmed with a range of -6.3% to 12.7%, while intra-day and inter-- day precision values were ≤14.4%. Additionally, recoveries were greater than 86.5% for each compound without significant matrix effects. The currently established analytical method exhibited great potential for the evaluation of plasma concentrations of methotrexate, tofacitinib and M9 simultaneously, greatly reducing the detection time, which would serve as a supplementary role in formulating dose decisions to achieve personalized treatment, identify drugs that cause adverse reactions and finally, to assess drug-drug interactions on clinical studies.

Broad‐spectrum and sensitive screening of more than 1000 compounds in equine urine using liquid chromatography/high‐resolution mass spectrometry

RationaleTo uphold the integrity of horseracing and equestrian sports, it is critical for an equine doping control laboratory to develop a comprehensive screening method to cover a wide range of target substances at the required detection levels in equine urine.MethodsThe procedure involved the enzymatic hydrolysis of 3 mL urine samples followed by solid‐phase extraction using HF Bond Elut C18 cartridge. The resulting extracts were then separated on a C18 reversed‐phase column and analyzed using liquid chromatography/high‐resolution mass spectrometry (LC/HRMS) in both electrospray ionization positive and negative modes in two separate injections. The analytical data were obtained in full scan and product ion scan (PIS) modes in an 11 min LC run.ResultsThe method can detect 1011 compounds (in both positive and negative ion modes). Over 95% of the target compounds have limits of detections (LODs) ≤10 ng/mL, and more than 50% of the LODs are ≤0.5 ng/mL. The lowest LOD can reach down to 0.01 ng/mL. The applicability of the method was demonstrated by the successful detection of prohibited substances in overseas and domestic equine urine samples.ConclusionsWe have successfully developed a regular screening method for equine urine samples that can detect more than 1000 compounds at sub‐ppb levels in both positive and negative ion modes with full scan and PIS using LC/HRMS. Furthermore, this method can theoretically be expanded to accommodate an unlimited number of prohibited substances in full‐scan mode.

Metroxylon sagu Rottb. Fruit Flour as Potential Prebiotics for Selected Probiotics and Phytochemical Profiling of its Methanolic Extract by LC-MS/MS

The plant of Metroxylon sago Rottb. which is found abundantly in Indonesia, Malaysia, Philippines, and Papua New Guinea, is famous as carbohydrate producing plants. The sago fruit has not been yet extensively used, although they are rich in oligosaccharides which is potential as prebiotic. Sago fruit flour was studied as growth substrate for five selected probiotics and phytochemical profile of its methanol extracts were determined. All bacteria grew well up to 24 h on the growth medium containing sago fruit flour as carbohydrate substitute. However, Lacticaseibacillus rhamnosus FNCC 0099 and Lactobacillus acidophilus FNCC 0051 showed viability stability up to 72 h, while the others were slightly decreased. The sago fruit flour contained 20.4 mg/g total sugars, 14.8 mg QE/g flavonoids, and 36.7 mg GAE/g phenolics. After extraction of the fruit flour with 80% methanol using an ultrasonicator at 55 °C at 40 kHz for 40 min, the extract was analysed for its phytochemical profiles using untargeted LC-MS/MS screening with negative ionization mode. Seven compounds categorised in three distinct groups i.e., sugar alcohol, plant glycosides and fatty acids, have been identified as having possible prebiotic activity. These include ((1xi)-1,5-anhydro-2,3,6-tris-O-(carboxymethyl)-1-methyl-4-O-methyl-D-glucitol), quercitrin, (15Z)-9,12,13-trihydroxy-15-octadecenoic acid, corchorifatty acid F, 3,5-dihydroxy-2-(4-hydroxyphenyl)-4-oxo-3,4-dihydro-2H-chromen-7-yl-hexopyranoside, gynocardin, and (4-methylumbelliferone)-b-D-glucopyranoside. As the sago fruit flour has been proved as potential prebiotic in this study, its extensive prebiotics activity, prebiotic index, and stability under digestive condition will be subjected for further study.

Effects of Combined Low-Dose Spironolactone Plus Vitamin E versus Vitamin E Monotherapy on Lipidomic Profile in Non-Alcoholic Fatty Liver Disease: A Post Hoc Analysis of a Randomized Controlled Trial.

Background/Objectives: Lipid dysmetabolism seems to contribute to the development and progression of nonalcoholic fatty liver disease (NAFLD). Our aim was to compare serum lipidomic profile between patients with NAFLD having received monotherapy with vitamin E (400 IU/d) and those having received combination therapy with vitamin E (400 IU/d) and low-dose spironolactone (25 mg/d) for 52 weeks. Methods: This was a post hoc study of a randomized controlled trial (NCT01147523). Serum lipidomic analysis was performed in vitamin E monotherapy group (n = 15) and spironolactone plus vitamin E combination therapy group (n = 12). We employed an untargeted liquid chromatography-mass spectrometry lipid profiling approach in positive and negative ionization mode. Results: Univariate analysis revealed 36 lipid molecules statistically different between groups in positive mode and seven molecules in negative mode. Multivariate analysis in negative mode identified six lipid molecules that remained robustly different between groups. After adjustment for potential confounders, including gender, omega-3 supplementation, leptin concentration and homeostasis model assessment-insulin resistance (HOMA-IR), four lipid molecules remained significant between groups: FA 20:5, SM 34:2;O2, SM 42:3;O2 and CE 22:6, all being higher in the combination treatment group. Conclusions: The combination of spironolactone with vitamin E led to higher circulating levels of four lipid molecules than vitamin E monotherapy, after adjustment for potential confounders. Owing to very limited relevant data, we could not support that these changes in lipid molecules may be beneficial or not for the progression of NAFLD. Thus, mechanistic studies are warranted to clarify the potential clinical significance of these findings.

Charge Motion in Solid Helium

We overview and discuss several advances in the understanding of the motion of ions through solid helium. Positive and negative ions in solid helium are microscopic complexes with internal structures embedded into the host crystal lattice. Their low-field mobilities normally decrease with cooling in both bcc and hcp crystals of either isotope of helium (3\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$^3$$\\end{document}He and 4\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$^4$$\\end{document}He). Depending on the density of solid helium (as well as, in the case of positive ions in hcp 4\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$^4$$\\end{document}He, on the crystal orientation), the corresponding activation energies for the mobility of the two species of ions may or may not coincide, and they are found to be typically either equal to or about twice the vacancy creation energy. In strong electric fields, the field dependence of the drift velocity of ions is often nonlinear but monotonic. However, for positive ions in hcp 4\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$^4$$\\end{document}He, non-monotonic anomalies in both temperature and field dependences of the drift velocity were observed. We discuss these features within the framework of the theory of ion motion via inelastic scattering of low-energy vacancions put forward by Alexander Andreev and co-workers.

Numerical Analysis of the Breakdown Process of CF3I at Low Pressure

The breakdown of CF3I gas at low pressure is of significant importance for applications in fields such as aerospace and microelectronics. However, the DC low-pressure breakdown characteristics of CF3I remain underexplored. In this work, we utilize a one-dimensional implicit particle-in-cell/Monte Carlo collision (PIC/MCC) algorithm to investigate the complete DC breakdown process of low-pressure CF3I. Our model accounts for ion–molecule collisions, recombination reactions, and external circuit influences. The breakdown process is delineated into three stages: before breakdown, breakdown, and after breakdown. In the before-breakdown stage, both the density and energy of particles are low. In the breakdown stage, the rapid increase in electron density and energy accelerates ionization reactions, leading to successful breakdown. The circuit behavior transitions from capacitive to resistive, sharing voltage with the external resistance. In the after-breakdown stage, continued positive ion growth leads to the formation of a thin anode sheath and a negative plasma potential. Energy production, including heating power and secondary electron emission (SEE) power, balances with energy loss through collision and boundary absorption. Specifically, 62% of the total heating power comes from positive ions, 1.5% from negative ions, and approximately 85% of electron energy is lost via boundary absorption. Finally, we compare the Paschen curves of CF3I with those of SF6, providing insights that are beneficial for the application of CF3I as an SF6 alternative.

Negative Air Ions (NAIs) as Cognitive Rehabilitation Therapy for Cerebral Palsy Patients

Negative Air Ions (NAIs) as Cognitive Rehabilitation Therapy for Cerebral Palsy Patients

Development of UPLC–MS/MS method for the simultaneous quantification of valproic acid and phenytoin in human plasma and application to study pharmacokinetic interaction in epilepsy patients

Valproic acid and phenytoin are two prevalent antiepileptic medications known for their narrow indices and propensity for cardiovascular and respiratory system toxicity. Therefore, therapeutic drug monitoring (TDM) of valproic acid (VAL) and phenytoin (PHE) concentrations in patient plasma is extremely beneficial for improving clinical choices, avoiding adverse reactions, and optimizing treatment for individual patients. In this study, a rapid and sensitive ultra-performance liquid chromatographic tandem mass spectrometer (UPLC-MS/MS) method was developed and validated for the simultaneous quantitative determination of valproic acid (VAL) and phenytoin (PHE) in human plasma. Negative electron spray ionization (ESI-) mode with selective ion recording (SIR) was employed to determine the transitions of m/z 142.98 and m/z 250.93 for VAL and PHE, respectively. The internal standard (IS) betamethasone (BETA) was ionized using positive electron spray ionization (ESI+) and detected by multi-reaction monitoring (MRM) mode to obtain precursor ions and specific fragment ions for quantification, and the MRM transition was chosen to be m/z 393.17 → 355.16. The separation was performed using a Phenomenex Synergi Hydro-RP (4 μm, 250 × 4.6 mm, I.D.) with an isocratic mobile phase consisting of acetonitrile – water (75:25, v/v) at a flow rate of 0.8 mL/min. The column temperature was maintained at 25 °C. The lower limit of quantification of VAL and PHE was 3.6 μg/mL and 0.72 μg/mL, respectively, which resulted in a recovery of more than 85 % for most analytes. According to US-FDA bioanalytical technique validation, the specificity, intra- and inter-day precision and accuracy, matrix effect, carryover, dilution, and stability of all analytes were within acceptable ranges. This analytical method was successful in evaluating the levels of valproic acid and phenytoin in human plasma from epileptic patients.

LC-MS/MS Bioanalytical Procedure for Atrasentan in Human Plasma: Method Development and Validation

11ABSTRACTObjectives: The objective of this work is to establish a bioanalytical technique for the quantification of atrasentan. The employed methodology for the detection and quantification of atrasentan in human plasma has a high degree of specificity, sensitivity, and simplicity. Methods: Shimadzu pumps were utilized in conjunction with an Autosampler Agilent Zorbax XDB C18 2.1 × 50 mm, 5 μm column employed as a stationary phase to achieve the chromatographic separation. Acetonitrile (0.1% formic acid) and 5 mM ammonium formate made up the mobile phase, which was optimized to have a 70:30% v/v ratio. Isocratic elution was employed in the experiment, with a flow rate of 0.150 mL/min. The entire cycle took 3.0 minutes, using a 10 μL injection volume. Results: The detection procedure is executed utilizing positive ion mode electrospray ionization (ESI) mass spectrometry under atmospheric pressure. For atrasentan, the precursor to product ion transitions used for quantification was m/z 511.623 to 354.15 and for the internal standard, verapamil, m/z 455.22 to 165. 02. The retention times for atrasentan and verapamil were found to be 1.68 and 0.96 minutes, respectively.Conclusion: In accordance with the recommendations of the United States Food and Drug Administration (USFDA) and EMA, it was ascertained that the remaining validation parameters remained within the specified range.

High Throughput LC-MS/MS Method for the Quantitation of Mefenamic Acid in Rat Plasma by Protein Precipitation Technique Using 96 Well Plate Format

An advanced and validated high-throughput liquid chromatography-tandem mass spectrometry (LC-MS/MS) approach has been established to accurately determine the concentration of mefenamic acid in rat plasma. This method utilizes mefenamic acid D4 as the internal standard (ISTD). The analyte and ISTD underwent protein precipitation in a 96-well plate format and were then separated on a BDS Hypersil C8 column (3 μm, 100 x 4.6 mm) using a precise isocratic mobile phase of 2 mM ammonium formate by 0.1% formic acid and acetonitrile (30:70 v/v). The detection was performed on a triple quadrupole mass spectrometer utilizing positive ionization consideration. The approach demonstrated a concentration range of 20.659 to 20067.772 ng/mL, thru relative regaining reaching from 69.1 to 74.3%. The inter-batch precision was excellent, with a coefficient of variation (%CV) of ≤ 7.8%. Additionally, the inter-batch accuracy at four different quality control-points ranged from 97.0 to 100.4%, demonstrating high levels of accuracy. This method has been thoroughly validated and is extremely specific, accurate, and precise. It is perfectly suited for high-throughput investigation of mefenamic acid in rat plasma, making it ideal for routine analysis.