Spectroscopic analysis, molecular modeling, and machine-learning-guided binding-site prediction reveal the interaction mechanism of atropisomeric colchicine with lysozyme.

Analytical methods utilizing the donor-acceptor phenomenon for proguanil (PRGL), an antimalarial medication, that are straightforward, quick, and possess a wide linear dynamic range for drug quantification and its toxicity assessment have not been published in the literature. This study spectrophotometrically validated two economical and effective analytical methods based on the complexation of PRGL with π-acceptors, chloranilic acid (CHLA) and 7,7,8,8-Tetracyanoquinodimethane (TCNQ) along with its Insilco toxicity evaluation using ADMET tool. Multiple analytical variables were examined. The linear dynamic range was notably effective, spanning from 5 to 80 μg mL-1 for CHLA and from 2 to 30 μg mL-1 for TCNQ techniques. The solid charge transfer complexes produced were assessed through different analytical techniques, such as UV-DRS, Fourier transform infrared spectroscopy, TGA-DTA, and powder X-ray diffraction. This study investigated the biological evolution of charge transfer (CT) complexes through the analysis of BSA protein binding and antimicrobial activity. The interaction between the CT complex and BSA was revealed by UV - Vis spectral analysis. The antibacterial efficacy of both CT complexes demonstrates significant effects. The CT complexes may exhibit promising biological activity and could be considered for further investigation as potential bioactive candidates in future studies. The molecular docking results verified the outcomes of the experiment. The outcomes obtained are appropriate for estimating the PRGL in its pharmaceutical formulation. The developed method's greenness was evaluated according to the AGREE guidelines and found satisfactory.

An antiepileptic drug named rufinamide (RUF) is used to treat seizures caused by Lennox Gastaut Syndrome (LGS). Fully sustainable evaluated stability-indicating simple spectrophotometric and spectrofluorometric techniques combined with the first derivative for determining the quantity of rufinamide from RUF-Ninhydrin charge transfer complex by using ninhydrin as an acceptor and its oxidative degradation products, respectively. These methods have been created and thoroughly validated in accordance with ICH requirements. The discipline of pharmaceutical analysis requires diverse stability testing under various conditions. Solubility of RUF in different solvent as well as calorimetric method also performed to check the stability of RUF in different temperature conditions. The rufinamide-ninhydrin complex exhibits absorbance at 594 nm using spectrophotometer and the first derivative appeared at 640 nm. The RUF's fluorescence and the oxidative degradant (OXD) emission appeared at 406 and 426 nm, following the excitation at 373 and 368 nm respectively. By applying Δλ = 20 nm, first-order derivatization of synchronous spectra was able to resolve the overlap and determine rufinamide in the presence of its product of oxidative degradation at 398 nm. Both the developed methods verified linearity ranging from 12.5 to 200 μg mL-1 for spectrophotometer and 0.5-8 μg mL-1 for the spectrofluorimetric method. The limit of quantitation (LOQ) values were of 0.14 and 0.27 μg mL-1, while the limit of detection (LOD) values were 8.19 and 0.41 μg mL-1 for spectrophotometric and spectrofluorometric methods respectively. AGREE and analytical eco-scale was two of the tools used to assess and approve the proposed method's greenness.

For the assay of methylprednisolone (MP) in pharmaceutical formulation, a fluorescence-based spectroscopic approach is developed using the protein, human serum albumin (HSA). The structural alterations in human serum albumin (HSA) following its interaction with methylprednisolone (MP) (10-32 μg mL-1) were determined by spectroscopy, which included the use of fluorescence and synchronous fluorescence. The calibration curve was modeled using the fluorescence method. The devised approach has a limit of detection of 1.16 μg mL-1 and a limit of quantification of 3.535 μg mL-1 for MP estimation that is straightforward, sensitive, accurate, and selective. The reference approach and the suggested method were contrasted to show which was more appropriate for MP quality control in its dosage forms. The recovery data obtained from 99.63% to 100.0% for intra-day and 99.60-100.1%, for inter-day precision. The developed method showed remarkable sensitivity to dosage forms and real sample (urine), suggesting possible application, when applied to dose forms with a relative standard deviation of less than 2%.

Since 2019 the world has been in a combat with the highly contagious disease COVID-19 which is caused by the rapid transmission of the SARS-CoV-2 virus (severe acute respiratory syndrome coronavirus 2). Detection of this disease in an early stage helps to control its spread and management. To combat this epidemic with one-time effective medication, improved quick analytical procedures must be developed and validated. The requirement for accurate and precise analytical methods for the diagnosis of the virus and antibodies in infected patients has been a matter of concern. The global impact of this virus has motivated scientists and researchers to investigate and develop various analytical diagnostic techniques. This review includes the study of standard methods which are reliable and accredited for the analytical recognition of the said virus. For early detection of SARS-CoV-2 RNA, RT-PCR (Real-time reverse transcriptase-polymerase chain reaction) is an accurate method among other methods and, thus, considered as the "gold standard" technique. Here, we outline the most extensively used analytical methods for diagnosing COVID-19, along with a brief description of each technique and its analytical aspects/perspective.

Green silver nanoparticle-based spectrophotometric and spectrofluorimetric measurements for tioguanine (TG) determination are reported in this study as a reliable, non-toxic approach with a sensitive and effective green assembly. TG is an anti-cancer medication used to treat leukemia. Chemical-based method development for its analysis purpose may have a dangerous effect on the environment. Cleaner, more affordable methods have received a lot of attention lately. By using Box–Behnken design under a response surface approach, the factors essential for the synthesis of green silver nanoparticles were optimized. For the two approaches, experimental optimization resulted in linear dynamic ranges of 55–220 and 65–200 nM, respectively. The technique was sensitive enough to detect and quantify TG at concentrations of 6.6 and 12.4 nM, respectively. The devised method is validated by satisfactory findings for the statistical treatment of the analytical data in accordance with the ICH requirements. Green nanoparticle formation was supported by X-ray diffraction analysis, scanning electron microscopy, and infrared spectroscopy analysis. When the developed nanosensors were used with the formulations, the relative standard deviation achieved was less than 2

In this study, a ternary complex for levofloxacin determination in human lysozyme using the lacosamide as a binary component was employed. The ternary complex caused a decrease in fluorescence intensity of lysozyme by 31.51 % while in case of levofloxacin interaction alone with lysozyme, fluorescence intensity decreased by 54.58 %. This suggested that levofloxacin binding in a ternary complex produced less microenvironmental changes in lysozyme. The spectroscopic approach has been reported where fluores-cence, UV-visible, synchronous fluorescence and circular dichroism was used to know the structural changes in lysozyme after its interaction with levofloxacin (8.85-34.80 mu gmL-1). Box-Behnken design under response surface methodology was opted to optimize the experimental variables. The results from the molecular docking after structure optimization with DFT inferred that lacosamide did not compete with levofloxacin for amino acid residues. Thus, revealing the possibility of co-administration of these drugs in clinical studies. Circular dichroism method was used to model the calibration curve that was constructed between ellipticity (millidegree) as a function of wavelength vs concentration. The linearity lies in the range of 4-32 mu gmL-1. The developed method is simple, sensitive, accurate and selective for the estimation of levofloxacin with a limit of detection of 0.42 mu gmL-1 and limit of quantification of 1.26 mu gmL-1. The recovery data ranged from 99.56 -101.23 % and 99.1-100 % for intra-and inter-day pre-cision, respectively. The developed method was applied in dosage forms having less than 2 % relative standard deviation and displayed outstanding sensitivity towards dosage forms, thus revealing its poten-tial application.(c) 2022 Elsevier B.V. All rights reserved.

Circular dichroism (CD) methods have been developed for the analysis of luliconazole (LUC) using plant based silver nanoparticles (P-AgNPs). Cleaner and natural approach have found significant attention in recent times owing to their exceptional physicochemical characteristics. Utilizing FTIR, SEM, and XRD, the produced nanoparticles were analyzed. The produced P-AgNPs were then used to assay LUC in formulation drugs. Four CD methods are developed as zero order and second order derivative methods. Methods I and II are based on a normal CD scan (zero order) that produced calibration range from 2 - 16 μgmL-1 at 232 nm (positive band) and 299 nm (negative band), respectively. Methods III and IV are the second order derivative methods that are developed at 232 nm (negative band) and at 251 nm (positive band). Density functional theory study was done to comprehend the feasibility of the developed methods and to optimize the structure and energy gap that validated the experimental procedure. The LUC assay methods using the proposed CD approach are simple, sensitive and precise with a limit of detection for methods I, II, III and IV of 0.527, 0.428, 0.250 and 0.30 μgmL-1 and limit of quantification of 1.75, 1.42, 0.833 and 1.0 μgmL-1, respectively. For intra- and inter-day precision, the recovery data ranged from 99.48 to 101% and 99.37 to 101%, respectively. The methods were used in dosage forms that produced a relative standard deviation of less than 2% and the true bias (θL and θU) within ±2%, demonstrating the potential use of the developed methods.

The complex of pregabalin and N,N-dimethylformamide has been studied with magnetic resonance spectroscopy. NMR spectroscopy which is a well-acknowledged method in the field of chemistry from a larger view, but the utility exactly finds independent space in analytical chemistry. Taking this viewpoint, a precise, accurate and validated quantitative nuclear magnetic resonance (qNMR) method is proposed for an anti-convulsant and analgesic drug, Pregabalin. The instrumental optimization for the developed method was done using 400.13 MHz Bruker NMR spectrometer. Further, the experimental design approach was employed for the optimization of the experimental variables such as pregabalin concentration, acquisition time and number of scans using Box-Behnken design under response surface methodology. The analyte contents were evaluated at chemical shifts (d) 0.835 ppm and 1.583 ppm, respectively. The final acquisition parameters (90 degrees pulse angle, 4.0 s acquisition time, 10.0 s of relaxation delay time) prompted the analysis to be completed within 15 min. The method demonstrated good validation with impressive RSD values for intra-day assay 0.003 - 0.17% and for inter-day assay 0.001 - 0.04% with the recovery range of 99 - 101%. The LOD and LOQ were found to be 0.12 mg mL(-1) and 0.39 mg mL(-1), respectively. The attained results of the qNMR method were then compared with the spectrophotometric method. Subsequently, the statistical treatment of the analytical data of the comparison revealed no significant difference between both the methods. The high precision value in case of qNMR is the additional advantage. Thus, the developed method is precise, accurate and a suitable tool for quantitative studies in bulk drug and its formulations. (C) 2021 Elsevier B.V. All rights reserved.

Abstract For cilazapril (CLZ), analytical methods based on donor–acceptor phenomenon that are simple, rapid with broad linear dynamic range for the quantification of drug are not available in the literature. Considering the requirement for the methods, in this study, two economic, potent analytical methods based on the complexation of CLZ with π-acceptors, 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) and 2,5-dichloro-3,6-dihydroxy-p-benzoquinone (CA) were developed, validated, and studied spectrophotometrically. Various analytical data were discussed. The effects of experimental variables were optimized from the results of in silico technique, i.e. Box–Behnken design under response surface methodology. Linear dynamic range was significantly good in the range of 6–60 µg mL−1 and 20–260 µg mL−1 for DDQ and CA methods. Moreover, molecular docking studies corroborated the experimental results. Further, the methods were supplemented by the pharmaceutical and biological application for the quantitative assay of CLZ. Collectively, the results of the reported method of the analysis suggest that the developed approach is simple, sensitive, accurate and precise.

Nuclear magnetic resonance (NMR) is a rapid and accurate analytical tool for qualification and quantification. The capacity of NMR of being quantitative can also justify the calibration of other analytical methods. In pharmaceutical domain, quantitative NMR (qNMR) can be applied in the identification and quantification of drug simultaneously. The early drug development stage requires a minimum sample for analysis. Thus, priority should be given to utilize this technique to attain results with least investment, rapid analysis time and minimum sample consumption. This technique is a significant phenomenon to identify impurities, drug substance, residual solvents of in-process control (IPC) samples and characterizing the formulations. From an analyst's perspective, qNMR proved to be a routine practice in pharmaceutical industry to qualify any drug product. The absolute and relative methods offer great help in quantifying the component of interest in the process control samples and finished products. This review highlights the evolution of NMR application in the pharmaceutical industry, where determining the purity of drug substance, drug product and establishing the identity of impurities and its level are the challenging aspects. NMR in medicinal field emerging as a numero uno for Covid-19 severity detection and its dire consequences, accelerated vaccine development and the mapping of SAR-COV-2 RNA and proteins via chemical shift assignments.