Optimization of graphene polypyrrole for enhanced adsorption of moxifloxacin antibiotic: an experimental design approach and isotherm investigation.

The presence of antibiotics in water systems had raised a concern about their potential harm to the aquatic environment and human health as well as the possible development of antibiotic resistance. Herein, this study investigates the power of adsorption using graphene-polypyrrole (GRP-PPY) nanoparticles as a promising approach for the removal of Moxifloxacin HCl (MXF) as a model antibiotic drug. GRP-PPY nanoparticles synthesis was performed with a simple and profitable method, leading to the formation of high surface area particles with excellent adsorption properties. Characterization was assessed with various techniques, including Fourier-transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), X-ray diffraction (XRD) and Brunauer-Emmett-Teller (BET). Box-Behnken experimental design was developed to optimize the adsorption process. Critical parameters such as initial antibiotic concentration, nanoparticle concentration, and pH were investigated. The Freundlich isotherm model provided a good fit to the experimental data, indicating multilayer adsorption of MXF onto the GRP-PPY-NP. As a result, a high adsorption capacity of MXF (92%) was obtained in an optimum condition of preparing 30 µg/mL of the drug to be adsorbed by 1 mg/mL of GRP-PPY-NP in pH 9 within 1 h in a room temperature. Moreover, the regeneration and reusability of GRP-PPY-NP were investigated. They could be effectively regenerated for 3 cycles using appropriate desorption agents without significant loss in adsorption capacity. Overall, this study highlights the power of GRP-PPY-NP as a highly efficient adsorbent for the removal of MXF from wastewater as it is the first time to use this NP for a pharmaceutical product which shows the study's novelty, and the findings provide valuable insights into the development of sustainable and effective wastewater treatment technologies for combating antibiotic contamination in aquatic environments.

A Validated Ultra-Performance Liquid Chromatographic Method for the Simultaneous Determination of Nadifloxacin, Mometasone Furoate and Miconazole Nitrate in Their Combined Dosage Form and Spiked Human Plasma Samples.

Nadifloxacin, mometasone furoate and miconazole nitrate are formulated together as a topical antifungal dosage form. In this work, a reversed-phase ultra-performance liquid chromatographic method coupled with a diode array detector (RP-UPLC-DAD) was developed and validated to determine nadifloxacin, mometasone furoate and miconazole nitrate simultaneously in their bulk powder, in pharmaceutical preparation and in spiked human plasma samples. Separation was achieved on an ACQUITY UPLC C18 column of 2.2 µm particle size (2.1 × 100 mm) via isocratic elution using a mobile phase consisting of methanol, acetonitrile and water with ratio (50:20:30; v/v/v) and 0.1 g ammonium acetate, then pH was adjusted to (7.00) using acetic acid, flow rate 0.6 mL/min, temperature 30°C and UV detection at 220 nm. The method is linear in a range from 5 to 400 µg/mL for both nadifloxacin and miconazole nitrate and from 20 to 500 µg/mL for mometasone furoate. The method was validated according to the ICH guidelines then applied successfully to determine the mentioned drugs in their pharmaceutical preparation and spiked human plasma samples. For plasma samples, the results showed that the method can determine nadifloxacin, mometasone furoate and miconazole nitrate in human plasma samples with high accuracy and precision.

Exploiting steroid-cyclodextrin complexes for selective determination of Estradiol Valerate and Norethisterone Acetate by synchronous fluorescence spectrofluorimetry.

Inclusion complexes of ß-cyclodextrin with Estradiol valerate (EST) or Norethisterone acetate (NOR) have been utilized for synchronous fluorescence spectrofluorimetry. ß-cyclodextrin improves fluorescence intensity as well as water solubility of the studied drugs. Samples in aqueous medium adjusted with ammonia were used in synchronous fluorescence to resolve the overlapped emission spectra. The effects of ß-cyclodextrin concentration and Δ λ have been optimized for sensitive and selective analysis of EST and NOR binary mixture. Synchronous fluorescence intensity of the two drugs is measured at Δ λ of 70 nm. EST and NOR can be simultaneously determined at 230 nm and 270 nm, respectively. Calibration curves were linear over the ranges of 0.5-6.0 µg mL-1 and 0.2-2.0 µg mL-1 for EST and NOR, respectively. Official guidelines were followed to estimate the validation parameters of the proposed method. The detection limits were 0.08 µg mL-1 for EST and 0.007 µg mL-1 for NOR. The proposed method was successfully used for the analysis of EST and NOR in their commercial preparations and the obtained results revealed statistical agreement with those obtained by application of the reported method for both drugs. The proposed method is compared favorably to previously published method in terms of simplicity and hazardous solvent consumption.

LC-ESI-MS/MS identification and characterization of ponatinib in vivo phase I and phase II metabolites.

Ponatinib (Iclusig®) is a multi-targeted tyrosine kinase inhibitor (TKIs). It is active against T315I and other BCR-ABL mutants. Investigation of in vivo metabolism of ponatinib was done using Sprague Dawley rats by giving one oral dose of PNT (4.7 mg/kg) to each rat and urine samples were gathered at several time intervals from dosing. Filteration of urine samples was done through 0.45 µm syringe filters. Phase separation using ACN was applied for extraction of ponatinib related metabolites. Characterization and identification of one in vivo phase II metabolite and thirteen in vivo phase I of PNT were done using LC-MS/MS. Phase I metabolic reactions were reduction, N-demethylation, hydroxylation, N-oxidation, oxidation and amide hydrolysis. Phase II metabolic reaction was glucuronidation of hydroxyl benzyl metabolites of ponatinib. The major in vivo metabolic reactions were α hydroxylation and α oxidation at piperazine ring. Literature review revealed no articles that have been published on in vivo metabolism of ponatinib in Sprague Dawley rats or ponatinib in vivo phase I and phase II metabolites structural characterization and identification.

Characterization of in vivo metabolites in rat urine following an oral dose of masitinib by liquid chromatography tandem mass spectrometry.

Masitinib (MST) is an orally administered drug that targets mast cells and macrophages, important cells for immunity, by inhibiting a limited number of tyrosine kinases. It is currently registered in Europe and USA for the treatment of mast cell tumors in dogs. AB Science announced that the European Medicines Agency has accepted a conditional marketing authorization application for MST to treat amyotrophic lateral sclerosis. In our work, we focused on studying in vivo metabolism of MST in Sprague-Dawley rats. Single oral dose of MST (33 mg kg-1) was given to Sprague-Dawley rats (kept in metabolic cages) using oral gavage. Urine was collected and filtered at 0, 6, 12, 18, 24, 48, 72 and 96 h from MST dosing. An equal amount of ACN was added to urine samples. Both organic and aqueous layers were injected into liquid chromatography-tandem mass spectrometry (LC-MS/MS) to detect in vivo phase I and phase II MST metabolites. The current work reports the identification and characterization of twenty in vivo phase I and four in vivo phase II metabolites of MST by LC-MS/MS. Phase I metabolic pathways were reduction, demethylation, hydroxylation, oxidative deamination, oxidation and N-oxide formation. Phase II metabolic pathways were the direct conjugation of MST, N-demethyl metabolites and oxidative metabolites with glucuronic acid. Part of MST dose was excreted unchanged in urine. The literature review showed no previous articles have been made on in vivo metabolism of MST or detailed structural identification of the formed in vivo phase I and phase II metabolites.

LC-MS/MS method for the quantification of masitinib in RLMs matrix and rat urine: application to metabolic stability and excretion rate.

Masitinib (MST) is a selective tyrosine kinase inhibitor. Validated liquid chromatography tandem mass spectrometric method (LC-MS/MS) was developed for the quantification of MST in rat liver microsomes (RLMs) matrix. The developed method was applied to metabolic stability and excretion rate studies. Reversed phase liquid chromatography was used for resolution of MST and bosutinib (IS) using C18 (50 mm × 2.1 mm, 1.8 µm). Binary solvent system consisted of 35% solvent A (0.1% formic acid in H2O, pH: 3.2) and 65% solvent B (acetonitrile) used as mobile phase at flow rate of 0.25 mL with a total run time of 5 min. Injection volume was 5 µL. Generation of ions was done in positive ESI source and quantification of MST and IS were done using MRM mode. The developed method showed a linearity in the range of 5-200 ng/mL (r2 ≥ 0.9992) with LOQ and LOD of 0.25 and 0.76 ng/mL in RLMs. The intra- and inter-day precision and accuracy ranged from 0.95 to 1.49 and - 5.22 to 1.13%, respectively in RLMs. Rate of disappearance of MST during incubation with RLMs was almost linear allover incubation time. In vitro t1/2 was 50.38 min and CLin was 3.11 ± 0.2. The developed method was applied also to measure the rate of masitinib excretion in rat urine. The method can used for further pharmacokinetic studies of MST.

Liquid chromatography tandem mass spectrometry method for the quantification of vandetanib in human plasma and rat liver microsomes matrices: metabolic stability investigation.

Vandetanib (VNT) is a new oral tyrosine kinase inhibitor that acts mainly by inhibiting vascular endothelial growth factor receptor (VEGFR). Fast, specific, sensitive and validated LC-MS/MS was established for the determination of VNT in two various matrices including rat liver microsomes (RLMs) and human plasma. This method was applied in metabolic stability investigation of VNT. Resolution of two analytes was performed using C18 column and isocratic mobile phase composed of binary system of 10 mM ammonium formate (pH 4.1) and acetonitrile in a ratio of 1:1. The flow rate was set at 0.25 mL/min and total run time was 4 min with injection volume of 5 µL. Ions were generated by ESI source and analyzed by multiple reaction monitoring mode (basis for quantification) in the Agilent 6410 QqQ analyzer. The linearity of the established method ranged from 5 to 500 ng/mL (r2 ≥ 0.9996) in human plasma and RLMs. LOQ and LOD were 2.48 and 7.52 ng/mL, and 2.14 and 6.49 in human plasma and RLMs matrices. The intra-day and inter-day precision and accuracy were 0.66-2.66% and 95.05-99.17% in human plasma matrix while in RLMs matrix, ranged from 0.97 to 3.08% and 95.8 to 100.09%, respectively. In vitro half-life was 39.85 min and intrinsic clearance was 3.92 ± 0.28 mL/min/kg.

Spectrophotometric study of etodolac complexes with copper (II) and iron (III).

A rapid, simple, and selective method was developed for the determination of etodolac. The method depends on complexation of etodolac with copper (II) acetate and iron (III) chloride followed by extraction of complexes with dichloromethane and then measuring the extracted complexes spectrophotometrically at 684 and 385 nm in case of Cu (II) or Fe (III), respectively. Different factors affecting the reaction, such as pH, reagent concentration, and time, were studied. By use of Job's method of continuous variation, the molar ratio method, and elemental analysis, the stoichiometry of the reaction was found to be in the ratio of 1:2 and 1:3, metal:drug in the case of Cu (II) and Fe (III), respectively. The method obeys Beer's law in a concentration range of 2.00-9.00 and 0.50-2.00 mg/mL in case of Cu (II) and Fe (III), respectively. The stability of the complexes formed was also studied, and the reaction products were isolated for further investigation. The complexes have apparent molar absorptivities of about 32.14 +/- 0.97 and 168.32 +/- 1.12 for Cu (II) and Fe (III), respectively. The suggested procedures were successfully applied to the analysis of pure etodolac and its pharmaceutical formulations. The validity of the procedures was further ascertained by the method of standard additions, and the results were compared with other reported spectrophotometric methods and showed no significant difference in accuracy and precision.