Ensuring robustness in the quality of antibiotic susceptibility test discs for four novel antibiotics

Antibiotic susceptibility test (AST) discs are used as an in-vitro diagnostic tool to select the appropriate antibiotic to treat an infection. Generally, the concentration of the drug loaded on to the AST discs is measured by studying its activity against quality control organisms. This methodology has several limitations—it is time consuming, requires trained manpower, has a wider acceptance criteria of zone of inhibitions—causing ambiguity in judging smaller variations in drug concentration. To overcome these issues, we have developed and validated high-performance liquid chromatographic (HPLC) methods for the determination of strength of AST discs for in-house researched antibiotics, namely Levonadifloxacin/WCK 771, Nafithromycin/WCK 4873, Cefepime-Tazobactam/WCK 4282, and Cefepime-Zidebactam/WCK 5222. The drugs were extracted from the AST discs using an appropriate solvent. The developed methods are simple, accurate, precise, reproducible, rugged, and robust. They are efficient in terms of time, and can be easily conducted in a quality control laboratory during release as well as stability evaluation of AST disc. Application of HPLC methods for the determination of strength of AST discs ensures flawless quality and, consequently, a better selection of drugs to treat bacterial infections in clinics.     

Assay of tolnaftate and related impurities by isocratic supercritical fluid chromatography

Tolnaftate, an antifungal drug (TF) and related impurities arising from synthesis, viz., N-methyl-m-toluidine (NMmT) and beta-naphthol-1-chlorothio carbamate (beta-NCTC) can be determined by supercritical fluid chromatography. Even though it was possible to elute TF completely with neat SCF CO2, the peaks of the impurities were found to merge. The chromatographic figures of merit of the three analytes such as retention time (tR), capacity factor (k), selectivity factor (alpha), no. of theoretical plates (N), were optimized. The three compounds can be resolved in 5 min on a Hypersil (250 x 4.0 mm) 5 mu, C18 column with supercritical carbon dioxide, modified with 1.96% methanol as the mobile phase at 9.81 MPa and at 40 degrees C. Detection was carried out at 220 nm. The data as evaluated by the linear regression least squares fit method gave linearity ranges from 0.2 to 10.0 microg/mL for TF and NMmT and 0.3 to 10.0 microg/mL for beta-NCTC with correlation coefficients > 0.99. The method was successfully employed to estimate levels of 0.01% for NMmT and 0.02% for beta-NCTC with respect to TF.     

Metabolite identification by liquid chromatography-mass spectrometry

Metabolite identification (Met ID) is important during the early stages of drug discovery and development, as the metabolic products may be pharmacologically active or toxic in nature. Liquid chromatography-mass spectrometry (LC-MS) has a towering role in metabolism research.This review discusses current approaches and recent advances in using LC-MS for Met ID. We critically assess and compare various mass spectrometers, highlighting their strengths and limitations. Citing appropriate examples, we cover recent LC and ion sources, isotopic-pattern matching, hydrogen/deuterium-exchange MS, data dependent analyses, MS^E, mass defect filter, 2D and 3D approaches for the elucidation of molecular formula, polarity switching, and background-subtraction and noise-reduction algorithms. A flow chart outlines a comprehensive strategy for Met ID, including a focus on reactive metabolites.     

Downstream implicit schemes for advection

Downstream-weighted implicit difference schemes for pure advection are stable for Courant numbers λ ≥ 1. They are numerically diffusive when λ > 1.     

Qualitative cation analysis without removing interfering anions

Summary A scheme of cation analysis is presented where phosphate and organic acids do not interfere with the course of analysis. The method is standardised on 2–3 mg level, and the procedure is rapid. Group separations are neat and in no case the precipitate is gelatinous. Some confirmatory tests of the elements have been modified.

---

Zusammenfassung Ein Analysengang für Kationen wird angegeben, der durch Phosphat und organische Säuren nicht gestört wird und mit 2 bis 3 mg Probe rasch durchführbar ist. Die Gruppentrennungen verlaufen sauber, die Niederschläge sind in keinem Fall gallertig. Einzelne Nachweisreaktionen wurden modifiziert.

     

Raman correlation function for generalized M-diffusion model

A generalized version of Gordon's M-diffusion model for reorientation of molecules in dense phase was proposed by Duttagupta and Sood. They calculated the IR correlation function and compared it with a few experimental data. We calculate the Raman correlation function for this model and compare it with experimental data for OCS, N₂O in CCl₄, and CH₃I. We find that at short times, the agreement with the experimental data is much better than that for Gordon's M-diffusion model. We have also shown that, at long times the correlation function decays as an inverse power of time. However, the experimental correlation function at long times decays much faster.     

A point‐defect model of structural phase transitions in the ferroelastic superconductor Y-Ba-Cu-O

A point-defect model of structural phase transitions in YBa₂Cu₃O_{6 + x} is proposed. The model treats the basal-plane oxygen atoms as point defects. The treatment parallels the work of Alefeld and coworkers on ferroelasticity due to hydrogen in metals. The model predicts that the tetragonal-to-orthorhombic phase transition should be accompanied by precipitation into regions of high and low oxygen density, as well as high and low oxygen ordering. This is in agreement with experiment, as well as with the predictions of Khachaturyan's concentration-wave model. A new feature of the present model is the prediction of two characteristic temperatures related, respectively, to Snoek-type and Gorsky-type diffusive relaxations. Practical implications of the high diffusivity of the basal-plane oxygens include the easy fabricability of a bicrystal of Y-Ba-Cu-O such that the two components of the bicrystal are rotated by 90° with respect to each other, and are separated by a non-superconducting layer. Such a bicrystal can find applications as a Josephson-tunneling device.     

Measurement of the neutron capture cross-section of 238U using the neutron activation technique

The ²³⁸U(n, ??)²³⁹U reaction cross-section at average neutron energy of 3.7?±?0.3?MeV from the ⁷Li(p, n)⁷Be reaction has been determined using activation and off-line ??-ray spectrometric technique. The ²³⁸U(n, ??)²³⁹U and ²³⁸U(n, 2n)²³⁷U reaction cross-sections at average neutron energy of 9.85?±?0.38?MeV from the same ⁷Li(p, n)⁷Be reaction have been also determined using the above technique. The experimentally determined ²³⁸U(n, ??)²³⁹U and ²³⁸U(n, 2n)²³⁷U reaction cross-sections were compared with the evaluated data of ENDF/B-VII, JENDL-4.0, JEFF-3.1 and CENDL-3.1. The experimental values were found to be in general agreement with the evaluated value based on ENDF/B-VII, and JENDL-4.0 but not with the JEFF-3.1 and CENDL-3.1. The present data along with literature data in a wide range of neutron energies were interpreted in terms of competition between different reaction channels including fission. The ²³⁸U(n, ??)²³⁹U and ²³⁸U(n, 2n)²³⁷U reaction cross-sections were also calculated theoretically using the TALYS 1.2 computer code and were also found to be in agreement experimental data.