Quantification of sofosbuvir in human serum by liquid chromatography with negative ionization mass spectrometry using the parent peak and its source‐induced fragment: Application to a bioequivalence study

In the mass spectrometry of sofosbuvir, a new orally administered antihepatitis C drug, a weak peak is detected at the m/z value of the parent ion (m/z 530) as a result of in‐source dissociation and current methods to its quantification, is based on monitoring of the parent peak using ultra high‐performance liquid chromatography with tandem mass spectrometry. With these methods serum concentration of the drug is quantifiable only up to 4–5 h postdose. However, the fragmentation of the molecule generates a more stable ion at m/z 287 (base peak) with a signal intensity of about tenfold compared to the parent ion. Our study was aimed to improve sensitivity of analysis by acquisition of the m/z value of the daughter ion from which it originated instead of the parent molecule. This novelty allows us to measure serum concentrations of the drug for a longer time postdose and provides more opportunity for pharmacokinetic studies of sofosbuvir. Our method was linear over the concentration range of 2–2560 ng/mL of sofosbuvir in human serum with a limit of quantification of 2 ng/mL compared to 10 ng/mL reported previously. The coefficient variation values of both inter and intraday analysis were less than 13.8%, and the percentage error was less than 6.3.     

Enhancement of Fluorescence Intensity of Tramadol and Its Main Metabolites in LC Using Pre-Column Derivatization with 9-Fluorenylmethyl Chloroformate

Tramadol was found to exhibit weak fluorescence with a maximum emission at 300 nm when excited at 200 nm. Also, fluorescence spectra of the drug and its two main metabolites, O-desmethyltramadol and N-desmethyltramadol are not practically identical. Thus low and different sensitivities have been reported for the drug and its metabolites in previously published work. In the present method using 9-fluorenylmethyl chloroformate (FMOC-Cl) as labeling agent, equal and magnified fluorescence intensity were obtained for the analytes. The drug, its metabolites and an internal standard (oseltamivir phosphate) were extracted from serum by dichloromethane. Pre-column derivatization of the analytes was achieved using FMOC-Cl in the presence of borate buffer (0.1 M, pH 7.5). Liquid chromatography with a mobile phase consisting of a mixture of 0.05 M phosphate buffer containing triethylamine (2 ml L^?1; pH = 3.0) and methanol (54:46; v/v) and a Shimpack CLC-ODS column were used for analytical separation of the analytes. The fluorescence of the column effluent was monitored at an excitation and emission wavelengths of 265 and 315 nm, respectively. The analytical method was linear over the concentration range of 1.0–1,280 ng mL^?1 of the parent drug and its metabolites and limit of quantification of 1.0 ng mL^?1 was obtained for the analytes using 10 μL injection. The method validation was studied and the validated method applied in a bioequivalence study of 2 different tramadol preparations in 24 healthy volunteers.     

Efficient factors in protein modification: ADenosine deaminase esterification by woodward reagent K

Chemical modification of Adenosine Deaminase (ADA) with N-ethyl-5-phenyl isoxazoliom-3-sulfonate (Woodward’s reagent K) (WR-K) was studied using experimental and theoretical techniques. Reaction concentration ranges were 0.8–6 mM WR-K at pH 7.8 and 27 °C. It was observed that the maximum number of moles of esterified residues per mol of enzyme ( $ \bar v $ ) in this concentration ranges is 4. However, esterification of ADA does not affect the activity of ADA, suggesting that the active site residues are not esterified. Similar results were obtained when the active site was blocked with 0.1 mM erythro-9-(2-hydroxy-3-nonyl) adenine (EHNA), followed by esterification, as measured by enol ester formation using absorbance at 340 nm. A theoretical approach was employed to study the modification process using molecular dynamic simulation, MM and QM/MM minimization. A full ASA empirical model and B3LYP method were used to evaluate the relative stability of some species which may arise from the reaction of ADA with WR-K. Theoretical results have shown that five residues (Glu 244, Glu 121, Glu 337, Asp 127, Asp 338) can be possible cases for modification in reaction 1:1 between ADA and WR-K at $ \bar v = 1 $ . Glu 121 was possible initially modified in this process. Besides, it is specified that atomic accessible surface area cannot be an appropriate criterion in determination of primary sites which are modified by WR-K. Ultimately, it is clarified that among effective factors in modification of enzyme surface such as atomic accessible surface, stability of modified segment and local residues changes of ADA, latter factor plays a basic role in this process from kinetics and thermodynamics point of view.     

Determination of uranium,thorium and potassium contents of rock samples in Yemen

Uranium, thorium and potassium contents in 16 different rock samples from various sites in Republic of Yemen were determined using three different techniques of analysis: γ-spectrometry, Instrumental neutron activation analyses (INAA) and X-ray fluorescence (XRF). The concentration range for thorium, uranium and potassium were found to be from 9,810 ± 272 to 3.6 ± 1.3 ppm, 1,072 ± 40 to 1.2 ± 0.7 ppm and 11 ± 1 to 0.26 ± 0.05%, respectively.     

Decomposition and decoloration of a direct dye by electron beam radiation

The wastewaters released by textile industries to the environment contain hazardous compounds like toxic refractory dye stuff at high concentration. In this study, electron beam irradiation-induced decoloration and decomposition of C.I. Direct Black 22 aqueous solutions were investigated. The influences of absorbed doses and initial dye concentration on the percent of decoloration, COD and pH of the solutions are described. The results show that the direct dye solutions can be effectively degraded by electron beam irradiation.     

X-ray fluorescence analysis for the study of fragments pottery excavated at Tell Jendares site, Syria, employing multivariate statistical analysis

X-ray fluorescence analysis study of 44 archaeological pottery samples collected from Tell Jendares site north-west of Syria has been carried out. Four samples of the total previous investigated samples were obtained from the kiln found on Tell Jendares site. Seventeen different chemical elements were determined. The XRF results have been processed using two multivariate statistical cluster and factor analysis methods in order to determine the similarities and correlation between the selected samples based on their elemental composition. The methodology successfully separates the samples where three distinct chemical groups were discerned.     

Quantitative Analysis of Sertraline in Human Serum by LC with Fluorescence Detection After Pre-Column Derivatization with 4-Chloro-7-nitrobenzofurazan

An accurate and sensitive reversed-phase high-performance liquid chromatographic method for analysis of sertraline in human serum, using 4-chloro-7-nitrobenzofurazan as pre-column derivatization agent, is described. The drug and an internal standard (azithromycin) were extracted from serum by use of a mixture of diethyl ether and chloroform, and subjected to pre-column derivatization with the reagent. Analysis of the resulting derivatives was performed on a 250 mm × 4.0 mm cyano column with 63:37 (v/v) methanol–sodium phosphate buffer (0.05 M, pH 3.7) containing 2 mL L^?1 triethylamine as mobile phase. Detector response was monitored at excitation and emission wavelengths of 470 and 537 nm, respectively. The calibration plot was linear over the concentration range 2–640 ng mL^?1. The lower limits of detection and quantification were 0.5 and 2 ng mL^?1, respectively. The method was validated for specificity, sensitivity, linearity, precision, accuracy, and stability and shown to be accurate (intra-day and inter-day accuracy from 0.3 to 4.2%) and precise (intra-day and inter-day precision from 2.4 to 15.5%). The drug was detected at concentrations as low as 2 ng mL^?1 in 0.5 mL serum and the method described can be easily applied to human single-dose pharmacokinetic studies of sertraline.     

H2O2/SOCl2: a useful reagent system for the conversion of thiocarbonyls to carbonyl compounds

The H₂O₂/SOCl₂ reagent system has been used as a new and efficient reagent for deprotection of thiocarbonyls to carbonyl compounds. The salient features of this protocol are short reaction times, good chemoselectivity, clean reaction profiles, and simple work-up that preclude the use of toxic solvents.     

Carbon nanotubes,science and technology part (I) structure,synthesis and characterisation

Since their discovery in 1991 by the Japanese scientist “Sumio Iijima”, carbon nanotubes have been of great interest, both from a fundamental point of view and for future applications. Different types of carbon nanotubes can be produced in various ways. Economically feasible large-scale production and purification techniques are still under development. Carbon nanotubes are discussed in this review in terms of history, types, structure, synthesis and characterisation methods. Carbon nanotubes have attracted the fancy of many scientists worldwide. The unique and unusual properties of these structures make them a unique material with a whole range of promising applications.     

Two derivative-free projection approaches for systems of large-scale nonlinear monotone equations

This study proposes two derivative-free approaches for solving systems of large-scale nonlinear equations, where the underlying functions of the systems are continuous and satisfy a monotonicity condition. First, the framework generates a specific direction then employs a backtracking line search along this direction to construct a new point. If the new point solves the problem, the process will be stopped. Under other circumstances, the projection technique constructs an appropriate hyperplane strictly separating the current iterate from the solutions of the problem. Then the projection of the new point onto the hyperplane will determine the next iterate. Thanks to the low memory requirement of derivative-free conjugate gradient approaches, this work takes advantages of two new derivative-free conjugate gradient directions. Under appropriate conditions, the global convergence result of the recommended procedures is established. Preliminary numerical results indicate that the proposed approaches are interesting and remarkably promising.