scholarly journals Colistimethate Acidic Hydrolysis Revisited: Arrhenius Equation Modeling Using UPLC-QToF MS

Molecules ◽  
2021 ◽  
Vol 26 (2) ◽  
pp. 447
Author(s):  
Ioanna Dagla ◽  
Anthony Tsarbopoulos ◽  
Evagelos Gikas
Keyword(s):  
Arrhenius Equation ◽  
Biological Fluids ◽  
Optimal Dose ◽  
Ultra Performance Liquid Chromatography ◽  
Multidrug Resistant ◽  
Equation Modeling ◽  
Analytical Methodology ◽  
Indirect Determination ◽  
Complete Hydrolysis ◽  
C 50

Colistimethate (CMS), the prodrug of polymyxin E (colistin), is an antibiotic widely used as a last-line therapy against multidrug resistant Gram-negative bacteria, but little is known about its pharmacokinetics as its administration has stopped as a result of high neuro- and nephro-toxicity. The measurement of CMS levels in patients’ biological fluids is of great importance in order to find the optimal dose regimen reducing the drug toxicity. Until now, CMS assay methods are based on the indirect determination after its hydrolysis to colistin (CS). Herein, the aim is to find the optimal conditions for the complete hydrolysis of CMS to CS. The reaction was studied at accelerated conditions: 40 °C, 50 °C, and 60 °C, and the results were evaluated by assessing the Arrhenius equation and computation employing the Tenua software. A validated analytical methodology based on ultra-performance liquid chromatography (UPLC) coupled to a hybrid quadrupole time of flight (QToF) instrument is developed for the simultaneous measurement of CMS and CS. The current methodology resulted in complete hydrolysis, in contrast with the previously reported one.

scholarly journals Assessment of configurations and chemistries of bridged nucleic acids-containing oligomers as external guide sequences: a methodology for inhibition of expression of antibiotic resistance genes

2016 ◽  
Vol 1 (1) ◽  
Author(s):  
Alexis Jackson ◽  
Saumya Jani ◽  
Carol Davies-Sala ◽  
Alfonso J C Soler-Bistué ◽  
Angeles Zorreguieta ◽  
...  
Keyword(s):  
Nucleic Acids ◽  
Viral Infections ◽  
Biological Fluids ◽  
Antibiotic Resistance Genes ◽  
Rnase P ◽  
Multidrug Resistant ◽  
Nucleotide Analogs ◽  
Hybrid Compound ◽  
Target Mrna ◽  
Novel Treatments

Abstract External guide sequences (EGSs) are short antisense oligoribonucleotides that elicit RNase P-mediated cleavage of a target mRNA, which results in inhibition of gene expression. EGS technology is used to inhibit expression of a wide variety of genes, a strategy that may lead to development of novel treatments of numerous diseases, including multidrug-resistant bacterial and viral infections. Successful development of EGS technology depends on finding nucleotide analogs that resist degradation by nucleases present in biological fluids and the environment but still elicit RNase P-mediated degradation when forming a duplex with a target mRNA. Previous results suggested that locked nucleic acids (LNA)/DNA chimeric oligomers have these properties. LNA are now considered the first generation of compounds collectively known as bridged nucleic acids (BNAs) – modified ribonucleotides that contain a bridge at the 2ʹ,4ʹ-position of the ribose. LNA and the second-generation BNA, known as BNANC, differ in the chemical nature of the bridge. Chimeric oligomers containing LNA or BNANC and deoxynucleotide monomers in different configurations are nuclease resistant and could be excellent EGS compounds. However, not all configurations may be equally active as EGSs. RNase P cleavage assays comparing LNA/DNA and BNANC/DNA chimeric oligonucleotides that share identical nucleotide sequence but with different configurations were carried out using as target the amikacin resistance aac(6ʹ)-Ib mRNA. LNA/DNA gapmers with 5 and 3/4 LNA residues at the 5ʹ- and 3ʹ-ends, respectively, were the most efficient EGSs while all BNANC/DNA gapmers showed very poor activity. When the most efficient LNA/DNA gapmer was covalently bound to a cell-penetrating peptide, the hybrid compound conserved the EGS activity as determined by RNase P cleavage assays and reduced the levels of resistance to amikacin when added to Acinetobacter baumannii cells in culture, an indication of cellular uptake and biological activity.

Arrhenius equation modeling for the shelf life prediction of tomato paste containing a natural preservative

2017 ◽  
Vol 97 (15) ◽  
pp. 5216-5222 ◽  
Author(s):  
Seid Mahdi Jafari ◽  
Mohammad Ganje ◽  
Danial Dehnad ◽  
Vahid Ghanbari ◽  
Javad Hajitabar
Keyword(s):  
Shelf Life ◽  
Life Prediction ◽  
Arrhenius Equation ◽  
Equation Modeling ◽  
Natural Preservative ◽  
Tomato Paste ◽  
Shelf Life Prediction

scholarly journals Effect of pharmacokinetic/pharmacodynamic ratio on tigecycline clinical response and toxicity in critically ill patients with multidrug-resistant Gram-negative infections

2020 ◽  
Vol 8 ◽  
pp. 205031212095889
Author(s):  
Jesus Ruiz ◽  
Paula Ramirez ◽  
Esther Villarreal ◽  
Mónica Gordon ◽  
María Ángeles Sánchez ◽  
...  
Keyword(s):  
Clinical Response ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Total Bilirubin Level ◽  
Optimal Dose ◽  
Multidrug Resistant ◽  
Pharmacokinetic Parameters ◽  
Time Curve ◽  
Free Concentration ◽  
Gram Negative

Introduction: The information about the pharmacokinetics and optimal dose of tigecycline in critically ill patients with severe underlying diseases is limited and controversial. In this study, we evaluate the pharmacokinetic parameters of tigecycline in critically ill patients with multidrug-resistant Gram-negative infection and explore the association between the pharmacokinetic/pharmacodynamic ratio and treatment response. Methods: A prospective study was designed including critically ill patients treated with tigecycline for multidrug-resistant Gram-negative infections. Blood samples were collected at day 3–5 of treatment, and pharmacokinetics parameters were evaluated using NONMEM® software. Relationship between area under the free concentration–time curve and minimum inhibitory concentration ratio (fAUC/MIC) and treatment failure was evaluated. Association between tigecycline fAUC and hepatobiliary toxicity was also investigated. Results: Twenty-five critically ill patients were included in the study. In the pharmacokinetic model, weight and total bilirubin level were found to be significant predictors of tigecycline clearance. Fifteen (60.0%) patients achieved an fAUC/MIC ratio >4.5, seven (28.0%) an fAUC/MIC > 6.96 and only three (12.0%) an fAUC/MIC > 17.9. No differences in fAUC/MIC ratio were obtained between those patients with and without clinical failure (5.28 (IC95%: 2.57–7.94) vs 8.71 (3.57–13.84)). fAUC values were higher in those patients who suffered hepatobiliary disorders (7.63 (3.93–11.34) vs 17.63 (7.85–26.28) mg/L/h). Conclusion: An important percentage of critically ill patients with multidrug-resistant Gram-negative infection treated with tigecycline do not achieve an appropriate pharmacokinetic/pharmacodynamic value. Tigecycline fAUC seems to be associated with hepatobiliary disorders in this study population. The effect of fAUC/MIC ratio on clinical response remains unclear.

scholarly journals Characterisation of Vibrio Species from Surface and Drinking Water Sources and Assessment of Biocontrol Potentials of Their Bacteriophages

2020 ◽  
Vol 2020 ◽  
pp. 1-15
Author(s):  
Mpho Defney Maje ◽  
Christ Donald Kaptchouang Tchatchouang ◽  
Madira Coutlyne Manganyi ◽  
Justine Fri ◽  
Collins Njie Ateba
Keyword(s):  
Water Samples ◽  
Biofilm Formation ◽  
Tap Water ◽  
Multidrug Resistant ◽  
Biochemical Tests ◽  
Antibiotic Resistant ◽  
North West ◽  
The North ◽  
C 50 ◽  
Species Specific

The aim of this study was to characterise Vibrio species of water samples collected from taps, boreholes, and dams in the North West province, South Africa, and assess biocontrol potentials of their bacteriophages. Fifty-seven putative Vibrio isolates were obtained on thiosulfate-citrate-bile-salt-sucrose agar and identified using biochemical tests and species-specific PCRs. Isolates were further characterised based on the presence of virulence factors, susceptibility to eleven antibiotics, and biofilm formation potentials. Twenty-two (38.60%) isolates were confirmed as Vibrio species, comprising V. harveyi (45.5%, n = 10), V. parahaemolyticus (22.7%, n = 5), V. cholerae (13.6%, n = 3), V. mimicus (9.1%, n = 2), and V. vulnificus (9.1%, n = 2). Three of the six virulent genes screened were positively amplified; four V. parahaemolyticus possessed the tdh (18.18%) and trh (18.18%) genes, while the zot gene was harboured by 3 V. cholerae (13.64%) and one V. mimicus (4.55%) isolate. Isolates revealed high levels of resistance to cephalothin (95.45%), ampicillin (77.27%), and streptomycin (40.91%), while lower resistances (4.55%–27.27%) were recorded for other antimicrobials. Sixteen (72.7%) isolates displayed multiple antibiotic-resistant properties. Cluster analysis of antibiotic resistance revealed a closer relationship between Vibrio isolates from different sampling sites. The Vibrio species displayed biofilm formation potentials at 37°C (63.6, n = 14), 35°C (50%, n = 11), and 25°C (36.4%, n = 8). Two phages isolated in this study (vB_VpM_SA3V and vB_VcM_SA3V) were classified as belonging to the family Myoviridae based on electron microscopy. These were able to lyse multidrug-resistant V. parahaemolyticus and V. cholerae strains. These findings not only indicate the presence of antibiotic-resistant virulent Vibrio species from dam, borehole, and tap water samples that could pose a health risk to humans who either come in contact with or consume water but also present these lytic phages as alternative agents that can be exploited for biological control of these pathogenic strains.

Voltammetric method for determination of glutathione on a gold-carbon-containing electrode

2019 ◽  
Vol 85 (1(I)) ◽  
pp. 28-34
Author(s):  
A. S. Gashevskaya ◽  
E. V. Dorozhko ◽  
E. I. Korotkova ◽  
E. A. Pashkovskaya ◽  
O. A. Voronova ◽  
...  
Keyword(s):  
High Performance ◽  
Biological Fluids ◽  
Low Cost ◽  
Pharmaceutical Preparations ◽  
Electrochemical Methods ◽  
Voltammetric Method ◽  
Indirect Determination ◽  
Biochemical Processes ◽  
Glutathione Determination

Glutathione (GSH) is one of the most important thiol-containing antioxidants involved into various biochemical processes in the human body. Glutathione determination in biological fluids (saliva, urine, serum) and pharmaceutical preparations is rather important for clinical practice. Various analytical methods — spectrophotometry, fluorimetry, high-performance liquid chromatography, NMR spectroscopy, capillary electrophoresis and electrochemical methods — are widely used for this purpose. Electrochemical methods are characterized by easy implementation, low cost and possibility of miniaturization. The electrochemical behavior of reduced (GSH) and oxidized (GSSG) glutathione on a gold-carbon-containing electrode (AuCE) was studied using cathodic voltammetry with different methods of removing oxygen from an electrochemical cell: nitrogen sparging and addition of sodium sulfite (4 mol/dm3). It has been shown that traces of H2O2 that remain in the near-electrode layer on the AuCE even after oxygen removal influence the electrochemical properties of GSH at a cathode sweep of the potential from 0 to –1.8 V: GSH is oxidized by H2O2 to GSSG, the most important product of this reaction is O2. An indirect determination of GSH by the current of oxygen reduction in the Na2SO3 medium in the concentration range from 0.5 × 10–8 to 4.2 × 10–8 mol/dm3 with a detection limit of 2.5 × 10–9 mol/dm3 is proposed. The developed voltammetric method is approved for the determination of GSH in certain pharmaceutical preparations.

Clinical Experience with Aminoglycosides in Dialysis-Dependent Patients: Risk Factors for Mortality and Reassessment of Current Dosing Practices

2011 ◽  
Vol 45 (11) ◽  
pp. 1338-1345 ◽  
Author(s):  
Brett H Heintz ◽  
George R Thompson ◽  
William E Dager
Keyword(s):  
Risk Factors ◽  
Average Duration ◽  
Bloodstream Infections ◽  
Optimal Dose ◽  
Empiric Therapy ◽  
Multidrug Resistant ◽  
Gram Negative ◽  
Factors Associated ◽  
Aminoglycoside Therapy ◽  
Increased Risk

Background:: A resurgence of aminoglycoside use has followed the recent increase of multidrug-resistant gram-negative pathogens and is often needed even in the treatment of dialysis-dependent patients; however, studies evaluating the treatment of gram-negative infections with aminoglycosides, including the optimal dose, in the setting of dialysis are limited. Objective: To evaluate the current patterns of aminoglycoside use, including microbiologic and clinical indications, and identify risk factors associated with mortality in dialysis-dependent patients receiving aminoglycosides. Methods: Utilization, clinical, and microbiologic data were collected retrospectively over a 2-year period (July 2008-June 2010) for adults with a diagnosis of renal failure requiring dialysis and aminoglycoside therapy. Binary logistic and multivariate regression analyses were performed to identify risk factors for alt-cause 30-day mortality. Results: Ninety-five consecutive aminoglycoside courses in 88 patients met inclusion criteria for evaluation. A wide variety of clinical and microbiologic indications were documented. The average duration of aminoglycoside therapy was 5.2 days (range 1-42), the average duration of antimicrobial therapy was 13.5 days (1-60), and the all-cause 30-day mortality rate was 36.5%. Factors associated with all-cause 30-day mortality were gram-negative rod (GNR) bacteremia (OR 28.6; p = 0.035), advanced age (OR 8.5; p = 0.030), recent admission (OR 33.4; p = 0.038). and inadequate empiric therapy (OR 14.9; p = 0.024). Intravenous catheter removal was protective of all-cause 30-day mortality (OR 0.01; p = 0.005). A first pre-dialysis plasma concentration relative to the minimum inhibitory concentration (Cp:MIC) <6 mg/L (gentamicin/tobramycin) was associated with an increased risk of mortality (p = 0.026) upon subgroup analysis of dialysis-dependent patients with GNR bloodstream infections. Conclusions: Outcomes among dialysis-dependent patients who received aminoglycosides were below expectations. Various risk factors for mortality were identified, including retention of the catheter, inadequate empiric therapy, and a Cp:MIC <6 mg/L. Improved approaches to dosing of aminoglycosides in dialysis-dependent patients, including more aggressive dosing practices, should be urgently explored in attempts to maximize favorable patient outcomes.

Development and validation of a stability-indicating ultra-performance liquid chromatography (UPLC) method for doxycycline hyclate: an optimization of the analytical methodology for a medical countermeasure (MCM) drug

2018 ◽  
Vol 10 (16) ◽  
pp. 1842-1851 ◽  
Author(s):  
Adil Mohammad ◽  
Cheng H. Yen ◽  
Miah Schneider ◽  
Bryan Lowry ◽  
Firat Yerlikaya ◽  
...  
Keyword(s):  
Liquid Chromatography ◽  
Drug Product ◽  
Ultra Performance Liquid Chromatography ◽  
Doxycycline Hyclate ◽  
Analytical Methodology ◽  
Stability Indicating ◽  
Development And Validation ◽  
Rapid Quantification

Doxycycline hyclate drug product impurities and rapid quantification using a validated UPLC method.

scholarly journals Determination of eugenitin in mouse blood by ultra-performance liquid chromatography-tandem mass spectrometry and its application to a pharmacokinetic study

2021 ◽  
Author(s):  
Chongliang Lin ◽  
Dezhen Song ◽  
Haodong Jiang ◽  
Lvqi Luo ◽  
Xi Bao ◽  
...  
Keyword(s):  
Biological Fluids ◽  
Multiple Reaction Monitoring ◽  
Internal Standard ◽  
Ultra Performance Liquid Chromatography ◽  
Quantitative Detection ◽  
Syzygium Aromaticum ◽  
Mouse Blood ◽  
The Matrix ◽  
Liquid Chromatography Tandem Mass

Abstract Eugenitin is a non-volatile chromone derivative which is always found in dried flower buds of Syzygium aromaticum L. (Merr.) & L.M. Perry. Until now, there were no reports about the pharmacokinetics of eugenitin in biological fluids. A UPLC-MS/MS method developed to determine eugenitin in mouse blood. The blood samples were prepared by protein precipitation with acetonitrile. Chrysin (internal standard, IS) and eugenitin were gradient eluted by mobile phase of acetonitrile and water (0.1% formic acid) in a BEH C18 column. The multiple reaction monitoring (MRM) of m/z 221.1→206.0 for eugenitin and m/z 255.1→152.9 for IS with an electrospray ionization (ESI) source was used for quantitative detection. The calibration curve ranged from 0.5 to 500 ng/mL (r > 0.995). The accuracy ranged from 98 to 113%, the precision was less than 12%, and the matrix effect was between 86 and 94%, the recovery was better than 81%. The developed method was successfully used for pharmacokinetics of eugenitin in mice after intravenous (5 mg/kg) and oral (20 mg/kg) administration, and the absolute availability of eugenitin was 12%.

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