Ecological spectroscopic methodologies for quantifying co-administered drugs in human plasma by photochemical quantum mechanical simulation.

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.

Innovative and sustainable deconvoluted amplitude factor spectrophotometric method for the resolution of various severely overlapping pharmaceutical mixtures: Applying the complex-GAPI-tool.

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.

Green Prospective Approach of Chromium Zinc Oxide Nanoparticles for Highly Ultrasensitive Electrochemical Detection of Anti-hypotensive Medication in Various Matrices.

A highly ultrasensitive sensor that relied on Cr/ZnO-NPs was developed to detect etilefrine hydrochloride (ETF) in different matrices via a particular green voltammetric technique. The X-ray diffraction pattern showed the nanomaterials of the polycrystalline hexagonal structure. The energy-dispersive X-ray spectrum approved the presence of Cr3+ inside the host zinc oxide framework. The morphological and topological characteristics were visualized using transmission electron microscopy and atomic force microscopy micrographs describing the nanoparticles in spherical-like shape with large-surface area. The energy gap (Eg) was evaluated from transmittance (T %) and reflectance (R %) spectra within the visible region. The optimization study indicated that the Cr/ZnO-NP/CPE sensor has high sensitivity, thanks to the distinctive physical and chemical properties of the fabricated electrode. A new approach showed a great selectivity for determining ETF in different matrices in the presence of other interferents like levodopa. Under optimal circumstances, the square-wave voltammetry revealed a linear response to ETF from 0.01 to 10 µmol L-1 (r = 0.9996) with quantification and detection limits of 9.11 and 2.97 nmol L-1, respectively. Finally, the proposed approach was effectively applied to estimate ETF in pharmaceutical dosage forms and biological fluids using simple, accurate, and selective electrochemical electrode. The greenness profile assessment of the developed method was performed using the Eco-Scale and green analytical procedure index. These tools indicated that the proposed method is an eco-friendly technique for the determination of ETF in different matrices.

Eco-Friendly UV-Spectrophotometric Methods Employing Magnetic Nano-Composite Polymer for the Extraction and Analysis of Sexual Boosters in Adulterated Food Products: Application of Computer-Aided Design.

BACKGROUND: Solid phase extraction (SPE) techniques, based on computationally designed magnetic-based multi-targeting molecular imprinted polymer (MT-MIP), combined with UV spectrophotometric approaches provide advantages in the examination of counterfeit samples. OBJECTIVE: The current work describes an innovative and sustainable methodology for the simultaneous determination of tadalafil (TAD) and dapoxetine hydrochloride (DAP) in aphrodisiac counterfeit products (honey and instant coffee) utilizing SPE exploiting MT-MIP. Additionally, an innovative UV spectrophotometric method capable of resolving TAD in its pharmaceutical binary mixtures with DAP was developed. A novel computational approach was implemented to tailor the synthesis and design of the MT-MIP particles. METHODS: We applied a newly developed UV spectrophotometric method which was based on a Fourier self-deconvolution (FSD) method coupled with the isoabsorptive point for determination of TAD and DAP in pharmaceutical dosage form. We also applied an SPE process based on MT-MIP designed particles, assisting in the analysis of both drugs in counterfeit food samples. The SPE process and the UV spectroscopic methodology were assessed regarding their greenness using the pioneering green analytical procedure index (GAPI), analytical greeness including sample preparation (AGREEprep) and AGREE tools. The synthesized MT-MIP particles were characterized by scanning electron microscopy and energy-dispersive x-ray spectroscopy. RESULTS: The suggested spectrophotometric methods revealed a wide linear concentration range of 2-50 µg/mL with lower LODs in the range of 0.604-0.994 µg/mL. Additionally, the suggested method demonstrated the utmost sensitivity and eco-friendliness for their target in its mixed dosage form and counterfeit food products. CONCLUSION: The SPE process and the developed analytical UV spectroscopic methodology were validated as per the ICH guidelines, and were found to be suitable for overseeing some counterfeiting activities in commercially available honey and instant coffee aphrodisiac products. HIGHLIGHTS: An SPE method based on MT-MIP magnetic-based polymer and a UV spectroscopic method were successfully developed for analysis of TAD and DAP in different matrices.

Chromatographic reversed HPLC and TLC-densitometry methods for simultaneous determination of serdexmethylphenidate and dexmethylphenidate in presence of their degradation products-with computational assessment.

Two Chromatographic methods have been established and optimized for simultaneous determination of serdexmethylphenidate (SER.DMP) and dexmethylphenidate (DMP) in the presence of their degradation products. The first method is a reversed phase high performance liquid chromatography with diode array detection (HPLC-DAD). Isocratic separation was carried out on Waters X-bridge Shield RP18 column (150×3.9×5 µm particle size) using a mixture of 5 mM phosphate buffer (pH 5.5): acetonitrile (40:60, v/v) as a mobile phase, flow rate 1 mL/min and detection at 220 nm. The second method is a thin-layer chromatography (TLC)-densitometry method using methanol: chloroform (70:30, v/v) as a mobile phase and UV scanning at 220 nm. In HPLC method, the linearity range of SER.DMP was (2.5-25 µg/mL); with LOD (0.051 µg/mL) and LOQ (0.165 µg/mL) while for DMP was (2.5-25 µg/mL); with LOD and LOQ of (0.098 µg/mL) and (0.186 µg/mL), respectively. For TLC method the sensitivity range of SER.DMP was (5-25 µg/mL), LOD was (0.184 µg/spot), while LOQ was (0.202 µg/ spot) whereas for DMP the sensitivity range was (5-25 µg/mL) with LOD of (0.115 µg/ spot) and LOQ of (0.237 µg/ spot), respectively. SER.DMP was found to be equally labile to acidic and alkaline hydrolysis, whereas DMP was sensitive to acidic hydrolysis only. Both drugs were successfully determined in presence of acidic and basic degradants by the two developed methods (stability indicating assay method). Chromatographic separation of the degradation products was carried out on TLC aluminum silica plates 60 F254, as a stationary phase, using methanol: dichloroethane: acetonitrile (60:20:20 v/v), as a mobile phase. The degradation pathway was confirmed using TLC, IR, 1H-NMR and mass spectroscopy; moreover, the separation power was correlated to the computational results by applying molecular dynamic simulation. The developed methods were validated according to the International Conference on Harmonization (ICH) guidelines demonstrating good accuracy and precision. They were successfully applied for quantitation of SER.DMP and DMP in pure and capsule forms. The results were statistically compared with those obtained by the reported method in terms of accuracy, precision and robustness, and no significant difference was found.

Greenness-by-design approach for developing novel UV spectrophotometric methodologies resolving a quaternary overlapping mixture.

Greenness-by-design (GbD) is an approach that integrates green chemistry principles into the method development stage of analytical processes, aiming to reduce their environmental impact. In this work, we applied GbD to a novel univariate double divisor corrected amplitude (DDCA) method that can resolve a quaternary pharmaceutical mixture in a fixed-dose polypill product. We also used a genetic algorithm as a chemometric modeling technique to select the informative variables for the analysis of the overlapping mixture. This resulted in more accurate and efficient predictive models. We used a computational approach to study the effect of solvents on the spectral resolution of the mixture and to minimize the spectral interferences caused by the solvent, thus achieving spectral resolution with minimal analytical effort and ecological footprint. The validated methods showed wide linear concentration ranges for the four components (1-30 µg/mL for losartan, 2.5-30 µg/mL for atorvastatin and aspirin, and 2.5-35 µg/mL for atenolol) and achieved high scores on the hexagon and spider charts, demonstrating their eco-friendliness.

Computer-Aided Design of Eco-Friendly Imprinted Polymer Decorated Sensors Augmented by Self-Validated Ensemble Modeling Designs for the Quantitation of Drotaverine Hydrochloride in Dosage Form and Human Plasma.

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.

Potentiometric determination of mebeverine hydrochloride antispasmodic drug based on molecular docking with different ionophores host-guest inclusion as a theoretical study.

The scientific community has continued to pay particular attention to potentiometric sensors based on ion-selective membrane sensors as an energy-efficient, easy-to-use method suitable for microfabrication. To this end, potentiometric ion-selective sensors were used as an alternative green analytical instrument. Three distinct sensors relying on various ionophores were built and assessed. A cationic exchanger, tetra phenyl borate, was used in the polyvinyl chloride polymeric plasticized matrix using di octyl phthalate, where α, ß, and γ cyclodextrins were utilized as ionophores. A comparative potentiometric analysis was carried out using three ion-selective sensor designs: α, ß, and γ cyclodextrins sensors. ß-Cyclodextrin significantly reduced the detection limit and improved the discriminative performance of mebeverine hydrochloride (MBV) in the pharmaceutical dosage form over α- and γ-cyclodextrins in the presence of other interfering chemicals. Additionally, a significant connection was made between the practical perspective and a theoretical investigation based on computational research. Nernstian potentiometric results for the optimum sensor were obtained for MBV in the range of concentrations 1.0 × 10-2 to 1.0 × 10-6 M, its slope was -58.70 ± 0.12 mV per decade with lower detection limits 4.50 × 10-7 M. This computational molecular docking investigation clarified that the binding sites and modes were in good agreement with the experiment results. This investigation was applied to expect the interaction between MBV and the proposed sensors to ensure which ionophores were the best for MBV.

Micelle-Incorporated Liquid Chromatography in the Light of Green Chemistry: An Application for the Quality Control Analysis of Anti-Platelet Fixed-Dose Combinations.

BACKGROUND: Oral anti-platelet agents are the cornerstone of the treatment of multiple cardiovascular diseases and in the long-term prevention of their recurrence. OBJECTIVE: In the present work, we report a method based on micellar liquid chromatography coupled with ultraviolet detection (MLC/UV), for the simultaneous quantification of combined anti-platelet therapy namely, clopidogrel bisulfate (CPS), aspirin (ASP), together with salicylic acid (SA), in their pharmaceutical dosage form. METHODS: The incorporation of 0.1M polyoxyethylene 23 lauryl ether (Brij-35) as a surfactant into the mobile phase improved solute-mobile phase interaction allowing for minimal organic solvent utilization, enhanced resolution, and rapid analysis (7 min). Furthermore, we performed a comprehensive evaluation of the environmental impact caused by our procedures versus previously reported analytical procedures applied in the determination of CPS and ASP. The evaluation was made using the Eco-scale tool. RESULTS: The results of the developed method indicated the superiority of our procedures in terms of greenness without compromising the quality of performance characteristics. The method was linear in the range of 1-100 µg/mL with limits of detection of 0.28, 0.32, and 0.29 µg/mL for CPS, ASP, and SA, respectively. The developed method can also be utilized to test the purity and the stability of ASP in pharmaceutical formulations through monitoring SA as its main degradation product. CONCLUSION: The MLC/UV method was successfully applied to the quantitative analysis of CPS, ASP together with SA-as a main degradation product of ASP-in their pharmaceutical dosage form. HIGHLIGHTS: The developed method was successfully applied for the determination of clopidogrel bisulfate (CPS), aspirin (ASP), together with salicylic acid (SA), in their pharmaceutical dosage form.

Computational design for eco-friendly visible spectrophotometric platform used for the assay of the antiviral agent in pharmaceutical dosage form.

Nowadays, the analytical community is focusing on developing new analytical methods that incorporate principles of green analytical chemistry to reduce adverse impacts on the environment and humans. In this study, we focused specifically on establishing a correlated connection between theoretical and experimental applications via developing green, and eco-friendly visible spectrophotometric methods. These methods were relied on charge-transfer complexation (CTC) between ledipasvir and 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ), or chloranilic acid (CA) for sensitive colorimetric analysis of ledipasvir in the presence of sofosbuvir (Sofolanork plus®). The results were evaluated as modern computational chemistry using molecular modeling technology. At ambient temperature, the reactions for DDQ and CA took 15 and 10 min, respectively, to produce a purple red-colored solution with DDQ absorbing maximally at 588 nm and a purple-colored solution with CA absorbing maximally at 522 nm. Linearity was achieved for ledipasvir utilizing DDQ and CA in the concentration ranges of 8-80 µg.mL-1 and 40-400 µg.mL-1, respectively. The precision and accuracy of the methods mentioned were determined. Finally, the results were statistically compared to a previously published spectrophotometric technique, and no significant differences were found.

An eco-friendly modified methodology for the resolution of binary pharmaceutical mixtures based on self-deconvolution of the UV spectrophotometric spectra in the Fourier domain: Application of Fourier self-deconvolution in UV spectroscopy.

UV spectrophotometry is a rapid and robust technique in resolving several challenging pharmaceutical combinations. Several mathematical treatments are available for the resolution of complex multicomponent UV spectra as; wavelet transformation, derivatization, and deconvolution-curve fitting models. Fourier self deconvolution (FSD) is a mathematical computational methodology for resolving interfering signals in many disciplines and applications. In the current work, we describe a modified FSD based methodology in resolving different binary pharmaceutical mixtures, which overcome the complexity of applying the traditional deconvolution-curve fitting technique on UV spectroscopic spectral data. The current approach differs from the conventional FSD by using the individual spectra of each component as a probing tool to avoid artifacts or errors on the deconvoluted spectra for accuracy of determinations. The utilized approach managed to resolve the binary mixtures of telmisartan/hydrochlorothiazide and ramipril/hydrochlorothiazide in their pharmaceutical dosage forms. The advantage of the current methodology over the traditional deconvolution-curve fitting is the simplicity of application, less time consuming, no need for sophisticated software, and higher sensitivity as revealed by the limit of detection (LOD). The linear ranges for telmisartan, ramipril, and hydrochlorothiazide were 1-25 µg/ml, 5-35 µg/ml, and 1-10 µg/ml, respectively, and the LOD values were in the ranges of 0.067-0.747 µg/ml. The developed FSD approach was validated as per the ICH recommendations regarding the accuracy, precision, linearity, selectivity, and limits of detection and quantitation. The recoveries obtained from the proposed approach were statistically compared with the corresponding reported methods and found no statistical difference between the obtained results.

Lung Ultrasound Assisted Comparison of Volume Effects of Fluid Replacement Regimens in Pediatric Patients Undergoing Penile Hypospadias Repair: A Randomized Controlled Trial.

BACKGROUND: Effective perioperative fluid therapy is a great consideration. OBJECTIVES: Using lung ultrasound (LUS), this study evaluated the preference of the conventional and restrictive fluid replacement regimens for their volume impact in pediatric patients undergoing a relatively long procedure with limited volume loss (hypospadias repair). METHODS: Eighty pediatric patients scheduled for hypospadias repair surgery were enrolled for conventional (CG) or restrictive fluid management groups (RG). The CG obtained Ringer's lactate at the conventional calculated doses, while the RG obtained infusion of Ringer's lactate at a rate of 3 mL/kg/h. B-line numbers in the LUS, recovery score, urine output, blood pressure (BP), heart rate HR, and oxygen saturation (SpO2) were recorded. RESULTS: As evidenced by the LUS, RG showed a higher incidence of normal lung morphology with a mean and SD of 1.3 ± 2.2 for B-line numbers, whereas, in CG, they were 3.1 ± 2.2 with a P-value < 0.001. Urine output was 3.2 ± 0.8 and 2.9 ± 0.7 for CG and RG, respectively, with a P-value equal to 0.07. HR, BP, and SpO2 differences between groups were statistically insignificant. The recovery score was higher in RG (5.8 ± 0.4) than in CG (5.1 ± 0.8) at the first postoperative 20 minutes, with a P-value < 0.001. CONCLUSIONS: In lengthy procedures with limited volume loss, using a moderately restrictive regimen is preferred over the conventional intraoperative fluid regimen considering both respiratory dysfunctions and recovery score.

Advanced eco-friendly UV spectrophotometric approach for resolving overlapped spectral signals of antihypertensive agents in their binary and tertiary pharmaceutical dosage form.

Cardiovascular disorders are among the foremost causes of death worldwide, especially hypertension, a silent killer syndrome that requires multiple drug therapy for proper management. This work presents novel and green spectrophotometric methods for the concurrent analysis of Amlodipine (AML), Telmisartan (TEL), Hydrochlorothiazide (HCTZ), and Chlorthalidone (CLO) in their pharmaceutical dosage form. The suggested methods were Fourier-self deconvolution, amplitude factor, and first derivative methods developed and validated for the simultaneous determination of a tertiary mixture of AML, TEL, and HCTZ in TELVAS 3D 80 mg tablet and a binary mixture of TEL and CLO in TELMIKIND-CT 40 tablets. The investigated methods revealed limits of detection 0.7283 µg/ml for AML and ranging from 0.0121 to 0.0433, 0.1547 to 0.1767 µg/ml and 0.0578 to 0.1262 µg/ml for TEL, HCTZ, and CLO, respectively.The greenness of the suggested techniques was examined by an eco-scale scoring method called the penalty points, which revealed that the methods were excellent green regarding several parameters as reagents, instrument, and waste safety. The introduced methods' validity was investigated by resolving prepared laboratory mixtures containing different AML, TEL, HCTZ, or TEL and CLO ratios. Furthermore, the introduced methods were ensured by the standard addition technique. Finally, the obtained results were statistically compared by the reported spectrophotometric methods, showing no significant difference concerning precision and accuracy.

Smart UV spectrophotometric methods based on simple mathematical filtration for the simultaneous determination of celecoxib and ramipril in their pharmaceutical mixtures with amlodipine: A comparative statistical study.

Two newly introduced pharmaceutical mixtures of amlodipine/celecoxib and amlodipine/ramipril were developed to manage hypertension and the associated osteoarthritis. The current work presents three newly developed UV spectrophotometric methods depending on minimal mathematical manipulations on the zero-order spectrum namely: absorption correction, induced dual-wavelength, and Fourier self deconvoluted method; for the simultaneous determination of celecoxib and ramipril in their pharmaceutical combined dosage forms with amlodipine. In absorption correction and induced dual-wavelength method, celecoxib and ramipril were determined at 253 and 222 nm for absorption correction and (251-270 nm) and (222-230 nm) for induced dual-wavelength method, respectively from the zero-order spectrum after calculating the absorption correction and equality factors for amlodipine. Amlodipine itself was determined at 361 nm from the zero-order spectrum in both methods. In Fourier self deconvoluted method, celecoxib and amlodipine zero-order spectra were deconvoluted, using the spectrophotometer software built-in Fourier wavelet function, and then was determined at 360 and 269 nm, respectively. The proposed methods were simple, accurate, and sensitive requiring minimal mathematical manipulations saving the time needed for analysis. The methods were linear over the range of (5-60 µg/ml), (5-30 µg/ml), and (5-110 µg/ml) for each of amlodipine, celecoxib, and ramipril, respectively. The limit of detection was in the range of (0.5781-0.7132 µg/ml) for amlodipine, (0.6497-1.0450 µg/ml) for celecoxib, and (0.0001-0.0003 µg/ml) for ramipril that indicated the sensitivity of these suggested methods. All methods were validated as per ICH recommendations regarding linearity, range, accuracy, precision, and selectivity. A statistical comparative study executed for the proposed methods with each other and with the reported methods showed no significant difference between the proposed methods and the reported methods.

Synchronous Spectrofluorimetry Coupled with Third-Order Derivative Signal Processing for the Simultaneous Quantitation of Telmisartan and Chlorthalidone Drug Combination in Human Plasma.

This study is the first to develop and optimize a method for the simultaneous determination of chlorthalidone (CLT) and telmisartan (TEL) in, human plasma samples as well as in their newly released pharmaceutical tablet form, (Telmikind-CT 40®). The method is based on measuring fluorescence intensity, employing synchronous fluorescence mode coupled to third-order derivative signal processing, 0.5% w/v cetyl trimethyl ammonium bromide was used as cationic surfactant to enhance the fluorescence signal intensity and improve method sensitivity. The third-order derivative synchronous spectra of CLT and TEL are well separated with two zero-crossing points which allowed for the determination of CLT and TEL at 362 nm and 351 nm, respectively. Different experimental parameters were carefully investigated and optimized, calibration curves were constructed over concentration ranges of 20-1200 ng.mL-1 and 5-800 ng.mL-1 for CLT and TEL respectively. The developed method is simple and rapid, analytical parameters were validated according to ICH guidelines and high sensitivity was achieved as represented by limits of detection (LOD) of 4.69 and 1.58 ng.mL-1 for CLT and TEL respectively.

Analysis of quinary therapy targeting multiple cardiovascular diseases using UV spectrophotometry and chemometric tools.

Herein, UV spectrophotometry assisted by multivariate chemometric analysis have been presented for quantitative determination of complex quinary therapy containing atenolol, ramipril, hydrochlorothiazide, simvastatin and aspirin without any prior separation. Such combination is very useful for treating various cardiovascular diseases (CVD) including high blood pressure, hypercholesterolemia in addition to its antiplatelet aggregating activity. Calibration (15 samples) and validation (10 samples) sets were prepared of different concentrations for these drugs via implementing partial factorial experimental design. The zero order UV spectra of these sets were recorded and then subjected for further chemometric analysis. Partial least square (PLS) with/without variable selection procedure i.e. genetic algorithm (GA) were employed to untangle the UV spectral overlapping of these mixtures. The performance of these chemometric techniques were compared in terms of accuracy and predictive abilities using cross-validation and external validation methods. It was found that PLS provides good recoveries with prompt predictive ability albeit GA-PLS exhibited better analytical performance owing to its capability to remove redundant variables i.e. the number of absorbance variables had been reduced to about 19-28%. The developed methods allowed reliable determination of such complex therapy in its laboratory prepared mixtures and pharmaceutical preparation within comparable results to those reported by HPLC method, posing these chemometric methods as valuable and indispensable analytical tools in in-process testing and quality control analysis of many pharmaceutical compounds targeting CVD.

Separation-free spectrophotometric platforms for rapid assessment of combined antiplatelet therapy in complex matrices.

Aim: To develop simple and rapid UV-spectrophotometric platforms for the simultaneous quantification of a binary mixture containing clopidogrel bisulphate (CPS) and aspirin (ASP) in complex matrices without prior separation. Experimental: Five mathematical models namely ratio-difference method, mean centering of the ratio spectra, dual wavelength, induced dual wavelength and H-Point Standard Addition method, were utilized for resolving spectral overlap by mathematical processing of ratio and zero-order absorption spectra. Analytes were extracted from tested matrices (whole blood, pharmaceutical formulations and dissolution media buffer) and quantified using the proposed methods. The methods were validated according to ICH guidelines. Results: The developed methods demonstrated limits of detection ranging from 0.67 to 1.09 µg/ml-1 for CPS and 0.49 to 0.71 µg.ml-1 for ASP. All proposed methods allowed for reliable determination of CPS and ASP in complex matrices within reported reference ranges, indicating their potential application for therapeutic drug monitoring and quality control testing.