Simultaneous quantification of atenolol and chlorthalidone in human plasma by ultra‐performance liquid chromatography–tandem mass spectrometry

A simple, sensitive and reproducible ultra‐performance liquid chromatography–tandem mass spectrometry method has been developed for the simultaneous determination of atenolol, a β‐adrenergic receptor‐blocker and chlorthalidone, a monosulfonamyl diuretic in human plasma, using atenolol‐d7 and chlorthalidone‐d4 as the internal standards (ISs). Following solid‐phase extraction on Phenomenex Strata‐X cartridges using 100 μL human plasma sample, the analytes and ISs were separated on an Acquity UPLC BEH C₁₈ (50 mm × 2.1 mm, 1.7 µm) column using a mobile phase consisting of 0.1% formic acid–acetonitrile (25:75, v/v). A tandem mass spectrometer equipped with electrospray ionization was used as a detector in the positive ionization mode for both analytes. The linear concentration range was established as 0.50–500 ng/mL for atenolol and 0.25–150 ng/mL for chlorthalidone. Extraction recoveries were within 95–103% and ion suppression/enhancement, expressed as IS‐normalized matrix factors, ranged from 0.95 to 1.06 for both the analytes. Intra‐batch and inter‐batch precision (CV) and accuracy values were 2.37–5.91 and 96.1–103.2%, respectively. Stability of analytes in plasma was evaluated under different conditions, such as bench‐top, freeze–thaw, dry and wet extract and long‐term. The developed method was superior to the existing methods for the simultaneous determination of atenolol and chlorthalidone in human plasma with respect to the sensitivity, chromatographic analysis time and plasma volume for processing. Further, it was successfully applied to support a bioequivalence study of 50 mg atenolol + 12.5 mg chlorthalidone in 28 healthy Indian subjects. Copyright © 2015 John Wiley & Sons, Ltd.     

DNA interaction,cytotoxicity and molecular structure of cobalt complex of 4‐amino‐N‐(6‐chloropyridazin‐3‐yl)benzene sulfonamide in the presence of secondary ligand pyridine

Novel cobalt complex of 4‐amino‐N‐(6‐chloropyridazin‐3‐yl)benzene sulfonamide (sulfachloropyridazine) has been synthesized and characterized by elemental analysis, FT‐IR spectroscopy and magnetic susceptibility (VSM). Cobalt complex of Sulfachloropyridazine (Co‐SCP) crystallized in monoclinic space group P2₁/n with Z = 4. The structure is solved by direct method and refined to R = 0.099 for 4720 reflections with I ?4σ(I). The results of FT‐IR spectra suggest the binding of cobalt atom to the sulfonamide ligand which is in agreement with the crystal structure determination. In crystal structure, molecule is linked via, C‐H … π, C‐Cl … π and π … π intermolecular interactions. The computational studies like the optimization energy and root means square deviation compare with single crystal structure, frontier molecular orbital (Homo‐Lumo energy) and binding energy of the Co‐SCP has been carried out using DFT/B3LYP level of theory in gaseous phase. Hirshfeld surfaces and the 2D‐fingerprint analysis are performed to study the nature of interactions and their measurable contributions towards crystal packing. The interaction of the complex with DNA is investigated using viscosity measurement and absorption titration studies. The result shows the complex bind to DNA with intercalative mode with high DNA‐binding constant (K_b). Also, in vivo and in vitro cytotoxic studies are performed using S. pombe cells and brine shrimp lethality bioassay. DNA‐cleavage study shows better cleaving ability of the complex.     

Thermal comparison and multi-objective optimization of single-stage aqua-ammonia absorption cooling system powered by different solar collectors

Journal of Thermal Analysis and Calorimetry - This paper presents the comprehensive thermodynamic modelling to compare the performance and optimization of single-stage NH3–H2O-type absorption...     

Synthesis and mesomorphic characterization of azoesters with a coumarin ring

We have synthesized a homologous series of azoesters consisting of a coumaryl moiety as the end group. Eleven derivatives of this series exhibit mesomorphism. The nematic mesophase is exhibited from ethyl homologue onward, while the smectic phase commences at the pentyl derivative and is exhibited along with the nematic phase up to the hexadecyl derivative. The N-I transition temperatures curves show the usual odd-even effect. All the compounds in this series are thermally stable and exhibit a wide mesomorphic range of nearly 120°C. Their thermal stabilities and other characteristics are discussed.     

UTLC: An Advanced Technique in Planar Chromatography

As part of increasing research in the field of separation science, there have been many efforts to undertake planar chromatography with more efficient separation and better resolution in the shortest period of time, together with a specificity and a capability to identify more precisely an unknown compound present in a mixture. Ultra-thin layer chromatography (UTLC) is a modern technique which gives separation within 10–30 mm and development in just 1–6 min, with the consumption of less solvent. The stationary phase of UTLC is made up of a silica gel monolithic layer of 10 μm thickness having 3- to 4-nm mesopores and 1- to 2-μm macropores. Glancing angle deposition (GLAD)-UTLC is a modification of UTLC which gives separation within 15 mm distance and in less than 2 min. Anisotropic media of GLAD UTLC gives a unique migration direction effect. UTLC atmospheric pressure–matrix-assisted laser desorption ionizer–mass spectrometery (UTLC-AP-MALDI-MS) is a choice of technique for the identification of an unknown compound in a mixture or an impure form. ULTC-AP-MALDI-MS allows the fast changing of plates, produces more intact protonated molecules, less fragmentation and less entry of chromatographic material, and yielding less complicated spectra than the vacuum condition. Thus, UTLC is a useful technique for very rapidly giving the separation and identification of new components present in mixtures. This review provides a brief overview of UTLC, the stationary phases used for UTLC, and the detection options and applications of UTLC.     

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.