Daptomycin: A Novel Macrocyclic Antibiotic as a Chiral Selector in an Organic Polymer Monolithic Capillary for the Enantioselective Analysis of a Set of Pharmaceuticals.

Daptomycin, a macrocyclic antibiotic, is here used as a new chiral selector in preparation of chiral stationary phase (CSP) in a recently prepared polymer monolithic capillary. The latter is prepared using the copolymerization of the monomers glycidyl methacrylate (GMA) and ethylene glycol dimethacrylate (EGDMA) in the presence of daptomycin in water. Under reversed phase conditions (RP), the prepared capillaries were tested for the enantioselective nanoliquid chromatographic separation of fifty of the racemic drugs of different pharmacological groups, such as adrenergic blockers, H1-blockers, NSAIDs, antifungal drugs, and others. Baseline separation was attained for many drugs under RP-HPLC. Daptomycin expands the horizon of chiral selectors in HPLC.

Toxicity Profile and Pharmacokinetic Study of Antibiotic Mixtures, Gentamicin and Vancomycin, in Rat Plasma by Ecofriendly Liquid Chromatography Coupled Tandem Mass Spectrometry.

The global burden of bacterial infection and antimicrobial resistance increases the demand to associate more than one antibiotic to fight life-threatening bacteria. Therefore, there is a great necessity to develop simple and sensitive methods for routine analysis of clinical samples. Therapeutic drug monitoring, bioequivalence, and pharmacokinetic studies are essential to ensure drug efficiency and safety. Herein, therefore, the first ecofriendly liquid chromatography -tandem mass spectrometry (LC-MS/MS) method was developed and fully validated for simultaneous determination of a commonly combined antibiotic for methicillin-resistant Staphylococcus aureus (MRSA), vancomycin (VCM) and gentamicin (GTM), in rat plasma after parenteral administration. VCM and GTM were extracted from plasma sample using acetonitrile (ACN)/0.1% TFA-induced protein precipitation followed by the separation on an Agilent Eclipse Plus ODS (3 mm × 100 mm, 3.5 µm) column using water-enriched mobile phase consisting of water containing 0.1% THF/ACN (85:15, v/v%) at flow rates of 0.30 mL min-1. The mass spectrometry parameters were optimized, and multiple reaction monitoring (MRM) in positive ion mode of two transitions was utilized for quantification of precursor to product ion at m/z 725.5 → 144 and 100.1 for VCM as [M + 2H]2+, 478.3 → 322.2 and 156.9 for GTM, and 586.3 → 162.9 and 425.3 for amikacin (AMK) internal standard, as [M + H]+. The current method has been validated as per U.S. FDA bioanalytical guidelines in terms of linearity, accuracy, precision, selectivity, recovery, matrix effects, and stability. The method was linear in the range of 1-2000 ng mL-1 and 1-1000 ng mL-1 with detection limits (S/N of 3) of 0.18 and 0.09 ng mL-1 for VCM and GTM, respectively. The selectivity and high sensitivity allow the current method to succeed in the study of pharmacokinetic parameters and drug-drug interaction between VCM and GTM after single-dose administration. VCM increased plasma clearance and elimination rate constant of GTM when coadministered and GTM also too. The change of serum chemistry analysis and significant elevation of creatinine and BUN indicate an alteration in kidney function in group III in those given the combined antibiotics. Our finding illustrated the nephrotoxicity of the two drugs when associated. The ecofriendly, simplicity, and rapidity of the current study made it a promising method for high-throughput biomonitoring in clinical samples.

Colistin Sulfate Chiral Stationary Phase for the Enantioselective Separation of Pharmaceuticals Using Organic Polymer Monolithic Capillary Chromatography.

A new functionalized polymer monolithic capillary with a macrocyclic antibiotic, namely colistin sulfate, as chiral selector was prepared via the copolymerization of binary monomer mixtures consisting of glycidyl methacrylate (GMA) and ethylene glycol dimethacrylate (EGDMA) in porogenic solvents namely 1-propanol and 1,4-butanediol, in the presence of azobisiso-butyronitrile (AIBN) as initiator and colistin sulfate. The prepared capillaries were investigated for the enantioselective nano-LC separation of a group of racemic pharmaceuticals, namely, α- and ß-blockers, anti-inflammatory drugs, antifungal drugs, norepinephrine-dopamine reuptake inhibitors, catecholamines, sedative hypnotics, antihistaminics, anticancer drugs, and antiarrhythmic drugs. Acceptable separation was achieved for many drugs using reversed phase chromatographic conditions with no separation achieved under normal phase conditions. Colistin sulfate appears to be useful addition to the available macrocyclic antibiotic chiral phases used in liquid chromatography.

Targeting methionyl tRNA synthetase: design, synthesis and antibacterial activity against Clostridium difficile of novel 3-biaryl-N-benzylpropan-1-amine derivatives.

The synthesis of a series of benzimidazole-N-benzylpropan-1-amines and adenine-N-benzylpropan-1-amines is described. Subsequent evaluation against two strains of the anaerobic bacterium Clostridium difficile was performed with three amine derivatives displaying MIC values of 16 µg/mL. Molecular docking studies of the described amines determined that the amines interact within two active site pockets of C. difficile methionyl tRNA synthetase with methoxy substituents in the benzyl ring and an adenine biaryl moiety resulting in optimal binding interactions.

Green chemometric-assisted UV-spectrophotometric methods for the determination of favipiravir, cefixime and moxifloxacin hydrochloride as an effective therapeutic combination for COVID-19; application in pharmaceutical form and spiked human plasma.

As pharmaceutical analysis progresses towards environmental sustainability, there is a growing need to enhance the safety and health conditions for analysts. Consequently, the incorporation of chemometrics into environmentally friendly analytical methods represents a promising approach. Favipiravir, cefixime, and moxifloxacin hydrochloride have been currently used in COVID-19 treatment. In this study, we develop spectrophotometric methods depending on chemometric based models to measure the levels of favipiravir, cefixime, and moxifloxacin hydrochloride in pharmaceutical preparations and spiked human plasma. It is challenging to determine favipiravir, cefixime, and moxifloxacin simultaneously because of overlap in their UV absorption spectra. Two advanced chemometric models, partial least square (PLS) and genetic algorithm (GA), have been developed to provide better predictive abilities in spectrophotometric determination of the drugs under study. The described models were created using a five-level, three-factor experimental design. The outcomes of the models have been thoroughly assessed and interpreted, and a statistical comparison with recognized values has been taken into consideration. The analytical eco-scale and the green analytical procedure index (GAPI) evaluation methods were also utilized to determine how environmentally friendly the mentioned models were. The outcomes demonstrated how well the models described complied with the environmental requirements.

Various techniques for resolving overlapping ultraviolet spectra of combination pharmaceutical dosage forms containing hydroxychloroquine and paracetamol.

Ten novel spectrophotometric approaches were developed for the initial examination of the Hydroxychloroquine and Paracetamol medications. These procedures are straightforward, specific, easy to use, and provide exact and accurate results. The determination was conducted through the utilization of several approaches, including zero order (dual wavelength, zero crossing, advanced absorption subtraction and spectrum subtraction), derivative (first derivative of zero crossing), ratio (ratio difference, ratio derivative) and mathematical (bivariate, simultaneous equation, and Q-absorbance) techniques. After undergoing validation in accordance with ICH criteria, it was established that each of these methods achieved acceptable levels of precision, repeatability, robustness, and accuracy. The advantages and disadvantages of each method are demonstrated, and the proposed and reported methodologies were statistically compared.

Eco-friendly novel deconvoluted synchronous spectrofluorimetric approach for the determination of favipiravir, levodropropizine and moxifloxacin hydrochloride as an effective therapeutic combination for COVID-19; application in laboratory prepared mixtures and spiked human plasma.

In this work, a green, fast, and simple synchronous spectrofluorimetric approach has been developed to simultaneously determine favipiravir, levodropropizine, and moxifloxacin hydrochloride as co-administered medications for COVID-19 treatment in pure form and spiked human plasma. The synchronous fluorescence spectroscopy technique to analyze the studied drugs at Δλ = 110 nm enabled the determination of levodropropizine at 360 nm. Then, applying Fourier Self-Deconvolution to each spectra to measure favipiravir and moxifloxacin hydrochloride at peak amplitudes of 431 nm and 479 nm, respectively, without any interference. Favipiravir, levodropropizine, and moxifloxacin hydrochloride could be sensitively determined using the described approach over concentration ranges of 20-300 ng/mL, 10-600 ng/mL, and 50-500 ng/mL, respectively. The method's validation was carried out effectively in accordance with guidelines recommended by the ICH. Finally, the Eco-scale and Green Analytical Procedure Index (GAPI) techniques have been used to evaluate the greenness of the proposed method.

Different methods for resolving overlapping UV spectra of combination medicinal dose forms of ciprofloxacin and metronidazole.

Four simple, specific, easy, precise and accurate spectrophotometric methods were developed for the first time to examine ciprofloxacin and metronidazole in combination, without having been separated beforehand by the developed methods. Ciprofloxacin and metronidazole were determined by utilizing advanced absorbance subtraction (AAS), spectrum subtraction, bivariate and ratio difference methods. Precision, repeatability, robustness, and accuracy were all determined to be within acceptable levels after each of these procedures underwent validation in accordance with ICH recommendations. Each method's benefits and drawbacks are illustrated, and the proposed and reported methodologies were statistically compared.

A Polymer-based Monolithic Capillary Column with Polymyxin-B Chiral Selector for the Enantioselective Nano-High Performance Liquid Chromatographic Pharmaceutical Analysis.

Herein, we report the first use of Polymyxin-B antibiotic as a enantio-selector in polymer monolithic capillary. The capillaries were functionalised, characterized and tested for the enantioselective nano-HPLC separation of 50 racemic pharmaceutical drugs. They have been easily prepared by immobilizing Polymyxin-B over the organic polymer for 48 h (P1) or encapsulating Polymyxin-B within the organic polymer (P2) and tested for the enantioselective resolution of racemic drugs. Acceptable resolution was achieved for 21 drugs using RP-HPLC conditions on both (P1) and (P2) capillary columns, while no separation was observed under NP-HPLC conditions. Polymyxin-B is commercially available, easily solubilized and stable in both acidic and neutral media. The developed Polymyxin-B-based polymer monolithic capillaries provide a promising expansion of platform in enantioselective HPLC separations.

Quality by design approach for development and validation of a RP-HPLC method for simultaneous estimation of xipamide and valsartan in human plasma.

A new rapid, simple, and sensitive RP-HPLC method was carried out through applying Quality by Design approach for determination of xipamide and valsartan in Human plasma. Fractional factorial design was used for screening of four independent factors: pH, flow rate, detection wavelength, and % of MeOH. Analysis of variance (ANOVA) confirmed that flow rate and % of MeOH were only significant. Chromatographic conditions optimization was carried out through using central composite design. Method analysis was performed using BDS Hypersil C8 column (250 × 4.6 mm, 5 µm) and an isocratic mobile phase of MeOH and 0.05 M KH2PO4 buffer pH 3 (64.5:35.5, v/v) at 1.2 mL/min flow rate with UV detection at 240 nm and 10 µL injection volume. According to FDA guidelines, the method was then validated for the determination of the two drugs clinically in human plasma in respect of future pharmacokinetic and bioequivalence simulation studies. The standard curve was linear in the concentration range of 5-100 µg/mL for both drugs, with a determination coefficient (R2) of 0.999. Also, the average recoveries lied within the range from 99.89 to 100.03%. The proposed method showed good predictability and robustness.

Different techniques for overlapped UV spectra resolution of some co-administered drugs with paracetamol in their combined pharmaceutical dosage forms.

Six simple, specific, accurate and precise spectrophotometric methods were developed for the first time analysis of some co-administered drugs with paracetamol in their mixture form without prior separation. Paracetamol & orphenadrine citrate were determined by using dual wavelength, bivariate, ratio difference, ratio derivative and mean centering of ratio spectra methods. Paracetamol & caffeine were determined by using ratio difference, ratio derivative and mean centering of ratio spectra methods. Paracetamol & diclofenac sodium were determined by using advanced absorption subtraction, ratio difference, ratio derivative and mean centering of ratio spectra methods. All of these methods were validated according to ICH guidelines where accuracy, precision, repeatability and robustness were found to be within the accepted limits. Advantages and limitations of each method are demonstrated and statistical comparison between the proposed methods was performed.

Functionalized polymer monoliths with carbamylated amylose for the enantioselective reversed phase nano-liquid chromatographic separation of a set of racemic pharmaceuticals.

Here we report the first encapsulation of three carbamylated amylose namely R-, S- and R/S-amylose 2,3(3,5-dimethylphenylcarbamate)-6-ethylphenylcarbamate in organic polymer monolith in situ capillary columns. The columns were investigated for the enantioselective nano-liquid chromatographic separation of a set of racemic pharmaceuticals, namely, α- and ß-blockers, anti-inflammatory drugs, antifungal drugs, norepinephrine-dopamine reuptake inhibitors, catecholamines, sedative hypnotics, antihistaminics, anticancer drugs, and antiarrhythmic drugs. Baseline separation was achieved for several drugs under reversed phase chromatographic conditions and only few drugs were separated under normal phase conditions. The developed columns provide more economical analysis under environmentally benign conditions.