RESUMEN
Urinary tract infections (UTIs) constitute the second most prevalent bacterial infections in the elderly demographic. The treatment landscape involves various antibiotics targeting the causative organisms; nevertheless, the emergence of resistance significantly impacts therapeutic effectiveness. Presently, a fixed-dose pharmaceutical combination is advocated to optimize patient outcomes by mitigating the risks of bacterial resistance and associated side effects. Ofloxacin (OFL) and cefpodoxime proxetil (CPD) combinations, co-administered with flavoxate hydrochloride (FLV), have demonstrated efficacy in UTI cases, offering relief from concomitant symptoms. In the pharmaceutical market, fixed-dose combinations have gained prominence, driven by advantages such as enhanced patient medication adherence and compliance. In the realm of analytical chemistry, the integration of green practices in the initial phases of method development is exemplified by the Greenness by Design (GbD) strategy. While univariate spectroscopic methods are conventionally considered suboptimal compared to chemometric techniques for resolving intricate mixtures, GbD approach, when applied to UV spectroscopy, enable univariate methods to attain comparable or superior outcomes. GbD adopts a systematic approach to optimize experimental conditions, minimizing environmental impact and maximizing analytical performance. Critical to GbD applications in UV spectroscopy is solvent selection, influencing spectral resolution and measurement sensitivity. GbD employs a combination of in-vitro and in-silico experiments to evaluate solute-solvent interactions with underlying photochemical quantum phenomena affecting the resulting spectral morphology, identifying an optimal compromise solvent with high resolution and minimal ecological impact. Consequently, it facilitates the efficient resolution of spectral overlapping and determination of complex mixtures in UV spectroscopy using univariate methods. Comparative analysis with chemometric techniques, acknowledged as potent spectral resolving methods, demonstrated that GbD-based univariate methods performed equivalently. The methodology was validated according to ICH recommendations, establishing a linear quantitation range (2-30 µg/mL) and a limit of detection (0.355-0.414 µg/mL) for the three drugs in human plasma. The greenness of the developed methodology was affirmed through the AGREE assessment protocol, confirming its environmentally conscious attributes.
RESUMEN
UV spectroscopy is considered the simplest, the most money and time investor technique in analytical research. Besides its lowered solvent and energy consumption leading to greener outcomes, its practicality is wide and suitable for a wide range of applications. Multicomponent mixtures are always representing themselves as a problematic challenge for any analytical technique fortunately UV spectroscopic methods found many ways to tackle these mixtures. Fourier self-deconvolution (FSD) was recently applied in UV spectroscopy as an effective tool for the resolution of binary mixtures unfortunately like any other method may fail to completely resolve severely overlapping mixtures. In this paper, we epitomize the newly developed deconvoluted amplitude factor (DAF) spectrophotometric approach which couples the concepts of both the FSD and the amplitude factor methods for the resolution of tadalafil (TAD) in its binary mixtures with dapoxetine hydrochloride (DAP) or tamsulosin hydrochloride (TAM). The embraced approach was assessed regarding its greenness utilizing different assessing protocols to give evident proof for its sustainability. The innovative approach showed an enhancement in the resolution of binary mixtures and showed high sensitivity as noticed from limits of detection and quantitation which were (0.374, 1.136 µg/mL), (0.269, 0.817 µg/mL), and (0.518, 1.569 µg/mL) for TAD, DAP, and TAM, respectively. The method was validated as per ICH guidelines recommendations and also was statistically compared with recently reported methods which revealed no statistically significant difference. A very handy and reader-friendly data presentation approach was followed for the ease of statistical data interpretation and evaluation.
RESUMEN
BACKGROUND: Computationally designed molecular imprinted polymer (MIP) incorporation into electrochemical sensors has many advantages to the performance of the designed sensors. The innovative self-validated ensemble modeling (SVEM) approach is a smart machine learning-based (ML) technique that enables the design of more accurate predictive models using smaller data sets. OBJECTIVE: The novel SVEM experimental design methodology is exploited here exclusively to optimize the composition of four eco-friendly PVC membranes augmented by a computationally designed magnetic molecularly imprinted polymer to quantitatively determine drotaverine hydrochloride (DVN) in its combined dosage form and human plasma. Furthermore, the application of hybrid computational simulations such as molecular dynamics and quantum mechanical calculations (MD/QM) is a time-saving and eco-friendly provider for the tailored design of the MIP particles. METHOD: Here, for the first time, the predictive power of ML is assembled with computational simulations to develop four PVC-based sensors decorated by computationally designed MIP particles using four different experimental designs known as central composite, SVEM-LASSO, SVEM-FWD, and SVEM-PFWD. The pioneering AGREE approach further assessed the greenness of the analytical methods, proving their eco-friendliness. RESULTS: The proposed sensors showed decent Nernstian responses toward DVN in the range of 58.60-59.09 mV/decade with a linear quantitative range of 1 × 10-7 - 1 × 10-2 M and limits of detection in the range of 9.55 × 10-8 to 7.08 × 10-8 M. Moreover, the proposed sensors showed ultimate eco-friendliness and selectivity for their target in its combined dosage form and spiked human plasma. CONCLUSIONS: The proposed sensors were validated in accordance with International Union of Pure and Applied Chemistry (IUPAC) recommendations, proving their sensitivity and selectivity for drotaverine determination in dosage form and human plasma. HIGHLIGHTS: This work presents the first ever application of both the innovative SVEM designs and MD/QM simulations in the optimization and fabrication of drotaverine-sensitive and selective MIP-decorated PVC sensors.