Simultaneous determination of novel β-lactamase inhibitor WCK 4234 and Meropenem in dog plasma by LC–MS/MS and its application to preclinical pharmacokinetic study

A precise and accurate liquid chromatography–tandem mass spectrometric (LC–MS/MS) bioanalytical method has been developed and validated for the simultaneous quantification of WCK 4234 and meropenem (MEM) in dog plasma. Protein precipitation using acetonitrile was employed as a sample preparation approach. Cefepime was used as an internal standard. The developed method was selective, sensitive (limit of quantification, 0.075 μg/ml for both drugs), accurate (recovery > 90%), precise (CV < 10%) and linear (r² ≥ 0.99, concentration range 0.075–120 μg/ml for both analytes). The developed method was successfully applied for the determination of both drugs in plasma to assess the pharmacokinetics in beagle dogs. WCK 4234 + MEM in a 1:1 ratio at 15 + 15 and 30 + 30 mg/kg doses were administered by the intravenous route. The mean plasma concentration and area under the concentration–time curve of WCK 4234 ranged from 38.3 to 77.4 μg/ml and from 47.8 to 77.1 μg h/ml, respectively, and the values for MEM ranged from 52.2 to 115.3 μg/ml and 70.5 to 133.6 μg h/ml respectively. The elimination half-life of WCK 4234 and MEM was around 0.8 h.     

Validated liquid chromatography–tandem mass spectrometry method for simultaneous quantitation of bendamustine and copanlisib in mouse plasma: Application to a pharmacokinetic study in mice

In this study, we report the development and validation of an LC–tandem mass spectrometry method for the simultaneous quantitation of bendamustine and copanlisib in mouse plasma as per the US FDA regulatory guidelines. The sample processing involves extraction of bendamustine and copanlisib along with internal standard (IS; warfarin) from 50 μL mouse plasma using a liquid–liquid extraction method. The chromatographic separation of bendamustine, copanlisib and the IS was achieved on an Atlantis dC₁₈ column using an isocratic mobile phase (5 mM ammonium acetate:methanol, 20:80 v/v). Bendamustine, copanlisib and the IS eluted at 0.88, 1.39 and 0.74 min, respectively, with a total run time of 2.5 min. The calibration curve ranged from 3.99–2996 and 4.33–3248 ng/mL for bendamustine and copanlisib, respectively. Inter- and intra-day precision and accuracy, stability in processed samples and upon storage, dilution integrity and incurred sample reanalysis were investigated for both the analytes. The intra- and inter-day precisions were in the ranges of 2.01%–5.05% and 2.74%–6.13% and 1.98%–7.64 and 8.62%–9.04% for bendamustine and copanlisib, respectively. Stability studies showed that both analytes were stable on bench top for 6 h, in auto-sampler for 24 and at −80°C for 30 days. The validated method was successfully applied to a pharmacokinetic study in mice.     

Investigation on Impurity Profiling and Degradation Behavior of WCK 771

Chromatographia - WCK 771 is a novel antibacterial drug recently launched in India for the treatment of acute bacterial skin and skin structure infections (ABSSSI). This report describes...     

Closo‐alanes (Al4H4, AlnHn+2, 4 ≤ n ≤ 8): A New Chapter in Aluminum Hydride Chemistry.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.     

Physicochemical studies on bioactive Cr(III) coordination compounds with esters of hydrazine carboxylic acid as hetero donor ligands

Reaction between hydrazine derivative ligands (HrzE) or (HrzB) and chromium salt in 1:2 (metal:ligand) molar ratio yielded monometallic trivalent coordination compounds with general formula [Cr(HrzE)₂X₂]X and [Cr(HrzB)₂X₂]X, where (HrzE) = hydrazine carboxylic acid ethyl ester, (HrzB) = hydrazine carboxylic acid tert-butyl ester, and X = Cl^?, Br^? or F^?. Elemental analysis, conductivity measurements, magnetic moment measurements, and various spectroscopic techniques, viz. infrared, ultraviolet–visible, and electrospray ionization mass spectrometry, were applied to illustrate the structure and composition of the coordination compounds. Analytic and conductivity results were consistent with 1:1 electrolytic behavior and the proposed formulas of the coordination compounds. Electronic absorption data and magnetic moment parameters indicated octahedral geometry surrounding the metal ion in the coordination compounds. The in vitro antimicrobial behavior of the ligands and coordination compounds was screened using four bacterial strains (Staphylococcus aureus, Bacillus subtilis, Escherichia coli, and Salmonella typhi) and two fungal strains (Candida parapsilosis and Saccharomyces cerevisiae). The results indicated improved activity of the coordination compounds compared with the free ligands against the studied bacteria and fungi.     

Synthesis and structural studies of complexes of Sb(III) and Bi(III) with thiosemicarbazones

Summary Several new complexes of Sb(III) and Bi(III) with thiosemicarbazones of furfuraldehyde, thiophene-2-carbaldehyde, indol-3-carbaldehyde and pyridine-2-carbaldehyde have been prepared and characterized by elemental analysis, conductivity, molecular weight determination and IR,¹H-and¹³C-NMR spectral studies. The ligands form complexes of the typeMX ₃ L[M=Sb(III) or Bi(III);X=chloride;L=ligand] which are found to be non-electrolytes inDMF. Spectral data indicate that the thiosemicarbazones act as bidentate ligands through the azomethine nitrogen and sulphur.

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Synthese und Strukturuntersuchungen an Komplexen von Sb(III) and Bi(III) mit Thiosemicarbazonen

Zusammenfassung Es wurden einige neue Komplexe von Sb(III) und Bi(III) mit Tiosemicarbazonen von Furfural, Thiophen-2-carbaldehyd, Indol-3-carbaldehyd und Pyridin-2-carbaldehyd hergestellt und mittels Elementaranalyse, Leitfähigkeitsmessungen, Molekulargewichtsbestimmungen und IR-,¹H- bzw.¹³C-NMR-Spektroskopie charakterisiert. Die Komplexe sind vom TypMX ₃ L[M=Sb(III) oder Bi(III);X=Chlorid;L=Ligand] und sind inDMF Nichtelektrolyten. Die spektroskopischen Daten zeigen, daß die Thiosemicarbazone als zweizähnige Liganden über den Azomethin-Stickstoff und Schwefel wirken.

     

BMIM[BF4]: An Efficient Ionic Liquid Medium for the Synthesis of Chromeno[b]pyridines as Potential Anticancer Agents

Russian Journal of Organic Chemistry - A series of 2-amino-4-aryl-5-oxochromeno[4,3-b]pyridine-3-carbonitriles have been synthesized with good yields (85–90%) by reacting...     

Monitoring the Reaction of the Body State to Antibiotic Treatment against Helicobacter pylori via Infrared Spectroscopy: A Case Study

The current understanding of deviations of human microbiota caused by antibiotic treatment is poor. In an attempt to improve it, a proof-of-principle spectroscopic study of the breath of one volunteer affected by a course of antibiotics for Helicobacter pylori eradication was performed. Fourier transform spectroscopy enabled searching for the absorption spectral structures sensitive to the treatment in the entire mid-infrared region. Two spectral ranges were found where the corresponding structures strongly correlated with the beginning and end of the treatment. The structures were identified as methyl ester of butyric acid and ethyl ester of pyruvic acid. Both acids generated by bacteria in the gut are involved in fundamental processes of human metabolism. Being confirmed by other studies, measurement of the methyl butyrate deviation could be a promising way for monitoring acute gastritis and anti-Helicobacter pylori antibiotic treatment.     

Brønsted acid catalyzed synthesis of 2-aryl-quinazolinones via cyclization of 2-aminobenzamide with benzonitriles in PEG

A simple and efficient Brønsted acid catalyzed synthesis of 2-aryl-quinazolinones via cyclization of 2-aminobenzamides with benzonitrile in PEG under metal and ligand-free condition. All substituted benzonitriles were also well participated with the formation of the corresponding products in moderate to good yields.