norhan badr

An in-line smartphone connected to a screen-printed selective electrode hand-held device was used to determine the concentration of distigmine bromide (DB) in its pure and dosage forms as well as its degradation kinetics by continuously measuring the change in the produced emf over time. The main objective, supported by the data presented, is to produce a highly reliable smartphone integrated selective sensor as a portable analyzer with potential high cloud connectivity combining a wide linear dynamic range, the fastest response time with the lowest limits of detection and quantitation while best integrating green analytical chemistry principles. The choice of ionophore used in this approach was guided by computation and the data obtained was compared with traditional analytical techniques. DB, for which there are no previously reported stability-indicating methods and for which four novel such methods are proposed here, was selected as a model drug for this work. At-line UV-spectrophotometry DB assay was obtained by measuring the difference between the spectra of the degradation product and the same concentration of intact drug. The degradation kinetics were studied by this method through tracking the decrease of DB absorbance and/or the increase of a generated degradation product signal over time. Off-line separation based HPLC and TLC stability-indicating methods for DB were also presented. All methods employed in this work were validated for accuracy, precision, specificity, repeatability, linearity, range, detection and quantification limits according to the ICH guidelines and were applied to the analysis of laboratory prepared mixtures as well as commercial products. While all methods proposed were shown to be highly reliable, the smartphone integrated selective sensor is highlighted as a portable analyzer with potential high cloud connectivity and was shown to combine a wide linear dynamic range, the fastest response time with the lowest limits of detection and quantitation while best integrating green analytical chemistry principles.

The methacholine challenge test is considered to be the gold standard bronchoprovocation test used to diagnose asthma, and this test is always performed in pulmonary function labs or doctors’ offices. Methacholine (MCH) acts by inducing airway tightening/bronchoconstriction, and more importantly, MCH is hydrolyzed by cholinesterase enzyme (ChE). Recently, the American Thoracic Society raised concerns about pulmonary function testing during the COVID-19 pandemic due to recently reported correlation between cholinesterase and COVID-19 pneumonia severity/mortality, and it was shown that cholinesterase levels are reduced in the acute phase of severe COVID-19 pneumonia. This work describes the microfabrication of potentiometric sensors using copper as the substrate and chemically polymerized graphene nanocomposites as the transducing layer for tracking the kinetics of MCH enzymatic degradation in real blood samples. The in-vitro estimation of the characteristic parameters of the MCH metabolism [Michaelis–Menten constant (Km) and reaction velocity (Vmax)] were found to be 241.041 μM and 56.8 μM/min, respectively. The proposed sensor is designed to be used as a companion diagnostic device that can (i) answer questions about patient eligibility to perform methacholine challenge tests, (ii) individualize/personalize medical dosing of methacholine, (iii) provide portable and inexpensive devices allowing automated readouts without the need for operator intervention (iv) recommend therapeutic interventions including intensive care during early stages and reflecting the disease state of COVID-19 pneumonia. We hope that this methacholine electrochemical sensor will help in assaying ChE activity in a “timely” manner and predict the severity and prognosis of COVID-19 to improve treatment outcomes and decrease mortality.

Supramolecular chemistry has gained an increasing attention in different disciplines of pharmaceutical community. Methacholine chloride (MCh) is a parasympathomimetic bronchoconstrictor which is a gold standard diagnostic tool for asthma through methacholine challenge test. The determination of MCh is a substantial analytical problem due to the lack of chromophore in its structure, therefore direct spectrophotometry becomes not possible for MCh quantification. In this work, we have exploited the high spectral absorptivity of 4-sulfocalix[4]arene (SCX4) and its exceptional complexation towards choline-mimetic guests to develop a method to quantify MCh. The host guest interaction between MCh and SCX4 produces an inclusion complex that can be investigated using different UV-spectrophotometric methods [dual wavelength method (DWM), ratio difference method (RDM) and ratio derivative method (1DD)]. The proposed methods are based on measurement of the manipulated absorbance of the formed complex peak after resolving the overlap from the host SCX4 spectrum followed by quantitation of MCh. Validation of the methods was performed in compliance with ICH guidelines, regression analysis showed good linearity over the concentration ranges of 10.0–150.0 μM for DWM and 10.0–170.0 μM for RDM and 1DD. The limit of quantification and detection were estimated to be 7.5 μM, 2.5 μM for DWM, 5.2 μM, 1.6 μM for RDM and 5.0 μM, 1.7 μM for 1DD, respectively. The complexation binding ratio and stability constant were calculated to be 1:1 and 7.20 × 104 ± 1.60 M−1, respectively, using continuous variation Job's method. Also, these methods have been used to determine MCh in Povocholine® formulation and in spiked human plasma. Moreover, the greenness of the proposed analytical procedures was evaluated by National Environmental Methods Index and Analytical Eco-Scale and the promising junction between the supramolecular chemistry and the eco-friendly spectrophotometric approaches was highlighted.

The major objective of this work was to develop a portable, disposable, cost-effective, and reliable POC solid-state electrochemical sensor based on potentiometric transduction to detect benzodiazepine abuse, mainly diazepam (DZP), in biological fluids. To achieve that, microfabricated Cu electrodes on a printed circuit board modified with the conducting polymer poly(3-octylthiophene) (POT) have been employed as a substrate. This polymer was introduced to enhance the stability of the potential drift (0.9 mV/h) and improve the limit of detection (0.126 nmol mL−1). Nernstian potentiometric response was achieved for DZP over the concentration range 1.0 × 10−2 to 5.0 × 10−7 mol L−1 with a slope of 55.0 ± 0.4 mV/decade and E0 ~ 478.9 ± 0.9. Intrinsic merits of the proposed sensor include rapid response time (11 ± 2 s) and long life time (3 months). In order to enhance the selectivity of the potentiometric sensor towards the target drug and minimize any false positive results, calix[4]arene (CX4) was impregnated as an ionophore within the PVC plastic ion-sensing membrane. The performance of the POC sensors was assessed using electrochemical methods of analysis and electrochemical impedance spectroscopy as a surface characterization tool. The studied sensors were applied to the potentiometric determination of DZP in different biological fluids (plasma, urine, saliva, and human milk) in the presence of its metabolite with an average recovery of 100.9 ± 1.3%, 99.4 ± 1.0%, 101.8 ± 1.2%, and 99.0 ± 2.0%, respectively.