Validated LC–MS/MS method for quantification of agomelatine in human plasma and its application in a pharmacokinetic study

An analytical method based on liquid–liquid extraction has been developed and validated for analysis of agomelatine in human plasma. Fluoxetine was used as an internal standard for agomelatine. A Betasil C18 (4.0 × 100 mm, 5 µm) column provided chromatographic separation of analytes followed by detection with mass spectrometry. The method involves simple isocratic chromatographic conditions and mass spectrometric detection in the positive ionization mode using an API‐4000 system. The proposed method has been validated with linear range of 0.050–8.000 ng/ml for agomelatine. The intra‐run and inter‐run precision values are within 12.12% and 9.01%, respectively, for agomelatine at the lower limit of quantification level. The overall recovery for agomelatine and fluoxetine was 67.10% and 72.96%, respectively. This validated method was used successfully for analysis of plasma samples from a pharmacokinetic study. Copyright © 2012 John Wiley & Sons, Ltd.     

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.     

Structure-based drug design,synthesis and screening of MmaA1 inhibitors as novel anti-TB agents

Molecular Diversity - Tuberculosis is one of the leading causes of death across the world. The treatment regimens for tuberculosis are well established, but still the control of the disease faces...     

Hölder exponents of irregular signals and local fractional derivatives

It has been recognized recently that fractional calculus is useful for handling scaling structures and processes. We begin this survey by pointing out the relevance of the subject to physical situations. Then the essential definitions and formulae from fractional calculus are summarized and their immediate use in the study of scaling in physical systems is given. This is followed by a brief summary of classical results. The main theme of the review rests on the notion of local fractional derivatives. There is a direct connection between local fractional differentiability properties and the dimensions/local Hölder exponents of nowhere differentiable functions. It is argued that local fractional derivatives provide a powerful tool to analyze the pointwize behaviour of irregular signals and functions.     

Highly sensitive extractive spectrophotometric determination of palladium(II) in synthetic mixtures and hydrogenation catalysts using benzildithiosemicarbazone.

A simple and highly sensitive method was developed for the extractive-spectrophotometric determination of palladium with benzilidithiosemicarbazone. The metal ion formed a reddish brown complex with benzildithiosemicarbazone in a potassium chloride-hydrochloric acid buffer of pH 2.5, which was easily extractable into methyl isobutyl ketone. The 1:1 complex showed the maximum absorbance at 395 nm with a Beer's law range of 0.25-3.5 ppm. The molar absorptivity and Sandell's sensitivity were found to be 3.018 x 10(4) dm3 mol(-1) cm(-1) and 0.0035 microg cm(-2), respectively. The correlation coefficient of the Pd(II)-BDTSC complex was 0.998, which indicated an excellent linearity between the two variables. The repeatability of the method was checked by finding the relative standard deviation (RSD) (n = 10), which was 0.46%. The instability constant of the complex calculated from Edmond and Birnbaum's method was 2.41 x 10(-5), that of Asmus' method is 2.53 x 10(-5) at room temperature. The interfering effects of various cations and anions were studied. The proposed method was successfully applied to the determination of palladium(II) in synthetic mixtures and hydrogenation catalysts. The validity of the method was tested by comparing the results with those obtained using an atomic absorption spectrophotometer.     

A New Mechanism for β‐Lactamases: Class D Enzymes Degrade 1β‐Methyl Carbapenems through Lactone Formation

β‐Lactamases threaten the clinical use of carbapenems, which are considered antibiotics of last resort. The classical mechanism of serine carbapenemase catalysis proceeds through hydrolysis of an acyl‐enzyme intermediate. We show that class D β‐lactamases also degrade clinically used 1β‐methyl‐substituted carbapenems through the unprecedented formation of a carbapenem‐derived β‐lactone. β‐Lactone formation results from nucleophilic attack of the carbapenem hydroxyethyl side chain on the ester carbonyl of the acyl‐enzyme intermediate. The carbapenem‐derived lactone products inhibit both serine β‐lactamases (particularly class D) and metallo‐β‐lactamases. These results define a new mechanism for the class D carbapenemases, in which a hydrolytic water molecule is not required.     

Effect of non-stoichiometry on the charge storage capacity of NiO conversion anodes in Li-ion batteries

Conversion anodes comprising non-stoichiometric black NiO suffer severe capacity fading in Li-ion batteries despite having a high Li⁺ ion diffusion coefficient. We attribute this capacity fading to (i) its small crystallite size (~?8 nm) and (ii) high charge transfer resistance (R_ct ~?60–180 Ω cm²). Small crystallites enhance grain boundaries which promote Li⁺ ion diffusion without efficient material utilization. In contrast, the stoichiometric green NiO anodes deliver a stable capacity of 280 mAh g^?1 over 50 charge-discharge cycles. The comparatively higher capacity of green NiO can be explained from its (i) large crystallite size (~?104 nm) and (ii) negligible R_ct values.     

Packing an equilateral polygon in a thin strip

LetP _m denote an equilateral polygon ofm sides with each side having length 1 and we allow the sides to cross and vertex repetitions. We consider the following question. What is the smallest widtht _m of a horizontal strip in the Euclidean plane that contains aP _m ? This problem has its origins in Euclidean Ramsey theory. Whenm is even, it is easy to see thatt _m =0. For a polygon with an odd number of sides, we prove that $\begin{gathered} t_{2n + 1} = \frac{{\sqrt {2n + 1} }}{{n + 1}} for 2n + 1 \equiv 3(\bmod 4) and \hfill \\ t_{2n + 1} = \sqrt {\frac{{2n + 1}}{{n^2 + 2n}}} for 2n + 1 \equiv 1(\bmod 4) \hfill \\ \end{gathered} $ respectively. Applying the result to unit distance graphs, we prove the following: SupposeG is a unit-distance graph, i.e.G can be drawn on the planeR ² such that each edge ofG is a straight line segment of length 1. IfG has no odd circuits of length greater than or equal to 15, thenX(G) ≤ 6, whereX(G) is the chromatic number ofG.     

Spectrophotometric determination of selenium by use of thionin

A simple, rapid, and sensitive spectrophotometric method has been developed for the determination of selenium in real samples of water, soil, plant materials, human hair, and synthetic cosmetic and in pharmaceutical preparations. The method is based on the reaction of selenium with potassium iodide in an acidic medium to liberate iodine. The liberated iodine bleaches the violet color of thionin, and which is measured at 600 nm. This decrease in absorbance is directly proportional to selenium concentration and obeys Beer's law in the range 1-5 micro g selenium in a final volume of 10 mL (0.1-0.5 microg mL(-1)). The molar absorptivity and Sandell's sensitivity of the method were found to be 7.33 x 10(4) L mol(-1) cm(-1) and 0.0011 microg cm(-2), respectively. The optimum reaction conditions and other analytical conditions were evaluated. The effect of interfering ions on the determination is described.